CN1751129A - Identification, monitoring and treatment of infectious disease and characterization of inflammatory conditions related to infectious disease using gene expression profiles - Google Patents

Abstract

A method is provided in various embodiments for determining a profile data set for a subject with infectious disease or inflammatory conditions related to infectious disease based on a sample from the subject, wherein the sample provides a source of RNAs. The method includes using amplification for measuring the amount of RNA corresponding to at least 2 constituents from Table 1. The profile data set comprises the measure of each constituent, and amplification is performed under measurement conditions that are substantially repeatable.

Description

Utilize gene expression atlas to identify, monitor and treatment infectious disease and the relevant inflammation of sign infectious disease

Technical field and background

The present invention relates to the application of gene expression data, especially relate in infectious disease identify, cause in monitoring and the treatment and by infectious disease or the sign of relative experimenter's inflammation and assessment in the application of gene expression data.

Existence or the disappearance of specific label when prior art has utilized gene expression data to determine specific Illnesses Diagnoses have also been described in some cases because the specified disease label is crossed and expressed and score accumulates so that the accuracy of diagnose or sensitivity raising. No matter from the efficient aspect of hygiene department's medical practice, or be conducive to regard to the patient with regard to improving diagnostic result, about any symptom of specific patient and patient have become a major issue in clinical medicine today to the information of the reaction of therapeutic agent or nutritional agents type and dosage.

Summary of the invention

In first embodiment, the method of collection of illustrative plates (profile) data group of suffering from the experimenter of the relevant inflammation of infectious disease or infectious disease based on experimenter's sample determination is provided, described sample provides the RNA source, described method comprises by amplification and detects corresponding to the amount of the RNA of at least two components in the table 1 and obtain the measured value of each component, wherein the spectrum data group comprise the measured value of each component and wherein amplification basically repeatably carrying out under the measuring condition.

In addition, the experimenter may have the doubtful symptom (presumptive signs) of general infection, comprise with respect to the rising of medical science standard white blood count, temperature rising, rhythm of the heart increase and blood pressure rising or at least a symptom in being reduced in, perhaps the inflammation relevant with infectious disease may be by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics's inspection or at least a the causing in treating.

In other embodiments, basically repeatably measuring condition can be within repeatability is higher than 5 percentage points degree, or repeatable be higher than 3 percentage points and all components amplification efficient basic simlarity, wherein said all components amplification efficient is in two percentage points or alternatively less than one percentage point. In this embodiment, sample can be selected from experimenter's blood, blood fraction, body fluid, cell mass and tissue.

In another embodiment, the method that infectious disease among the experimenter or the relevant inflammation of infectious disease is characterized based on experimenter's sample is provided, described sample provides the source of RNA, described method comprises the spectrum data group of assessing a plurality of members, each member is the quantified measures of the amount of certain distinct rna component in one group of selected component, thereby the measured value that makes described component can characterize the doubtful symptom of general infection, and this measured value of wherein said each component is repeatably obtaining under the measuring condition basically.

In addition, the experimenter may have the doubtful symptom of general infection, comprise occur with respect to medical science standard white blood count increase, temperature raises, the rhythm of the heart is accelerated and blood pressure raises or one of symptoms such as reduction, perhaps the experimenter may have with by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry gynemetrics checks or treatment in the doubtful sign of the relevant general infection of the inflammation that causes of at least a reason. In this embodiment, assessment can further comprise spectrum data group and baseline spectrum data group to the setting of this group are compared, baseline spectrum data group wherein and infectious disease to be characterized or the relevant inflammation-related with infectious disease.

In other embodiments, the amplification efficient of all components is basically similar, and infectious disease or the inflammation relevant with infectious disease infect from microorganism, more specifically be that bacterium infects, or eucaryon parasitic infection or virus infections or fungal infection, perhaps relate to systemic inflammatory response syndrome (SIRS). More specifically, infectious disease or the inflammation relevant with infectious disease can be from bacteremia, viremia virusemia or fungemias, the septicaemia that is perhaps caused by the microorganism of any classification. In addition, infectious disease or the inflammation relevant with infectious disease can relate to experimenter's local organization, and sample can from tissue or the fluid of the completely different type of this local organization.

Other embodiments comprise the spectrum data group are stored in the digital storage media, wherein store the spectrum data group and can comprise it is stored in the database as record.

Also have another embodiment to provide based on the method from infectious disease or the relevant inflammation of infectious disease among first sample assessment experimenter of experimenter, described sample provides the RNA source, described method comprises obtains first spectrum data group from first sample, the spectrum data group comprises a plurality of members, each member (member) is the quantified measures of distinct rna group component in one group of selected component, thereby so that can assess infectious disease or the relevant inflammation of infectious disease by the detection of these components, wherein the described measured value for each component is repeatably obtaining under the measuring condition basically. The method also comprises the calibration spectrum data group that produces for this group, wherein each member of calibration data group is each corresponding member of first spectrum data group and function for the corresponding member of baseline spectrum data group of this group, baseline spectrum data group wherein is with infectious disease to be assessed or the relevant inflammation-related of this infectious disease, with the spectrum data group of calibration as the comparison between first spectrum data group and the baseline spectrum data group, thereby experimenter's infectious disease or the relevant inflammation of infectious disease are assessed.

In relevant embodiment, the experimenter has the doubtful symptom of general infection, comprise with respect to medical science standard white cell count increase, temperature raise, heart rate is accelerated and blood pressure raises or the signs such as reduction at least a, perhaps infectious disease or inflammation may relate to by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics checks or the inflammation that causes of at least a reason wherein such as treatment.

In addition, baseline spectrum data group can be come comfortable one or more other samples that are different from the same experimenter who obtains under the condition of first sample, selectable condition is as follows: (i) time point that obtains of first sample, (ii) site that obtains of first sample, experimenter's biology situation when (iii) first sample obtains.

In addition, described one or more other samples can be in a period of time interval, namely between first sample and described one or more other samples, obtain at least one month, perhaps can be in a period of time interval, namely between first sample and described one or more sample, obtain at least ten two months, perhaps can before treatment is intervened or after the treatment intervention, obtain them. In this embodiment, first sample can come autoblood and baseline spectrum data group can be from tissue or the body fluid of the experimenter except blood. Perhaps first sample is from experimenter's tissue or body fluid, and baseline spectrum data group is come autoblood.

In other embodiments, baseline spectrum data group can be from one or more other samples of same experimenter, when being in from the sampling of first sample, the experimenter obtains under the different biology situation, namely with regard in the following factor with regard at least one: age, nutrition history, medical situation, clinical indication, medicine are processed, the exposure of activity, body weight and the environment of health, and baseline spectrum data group can be from one or more other samples of one or more not experimenters.

In addition, one or more different experimenters may have something in common at least a following factor: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure etc. of health. In other embodiments, clinical indication can be used for assessing one or more different experimenters' infectious disease or the relevant inflammation of infectious disease, also can comprise the calibration spectrum data group of at least a other clinical indication in the explanation context, wherein said at least a other clinical indication is selected from blood chemistry, urinalysis, X ray or other radiation or metabolic imaging technology, other chemical assay and physical examination.

In described embodiment, infectious disease or the inflammation relevant with infectious disease can infect from microorganism, bacterium infection, eucaryon parasitic infection, virus infections, fungal infection, perhaps the relevant inflammation of infectious disease or infectious disease can be from systemic inflammatory response syndrome (SIRS), from bacteremia, viremia virusemia, fungemia or the septicaemia that caused by the microorganism of any classification.

In other embodiments, functional relation is mathematical function and is different from simple difference, comprises the quadratic function of the corresponding member of first spectrum data group and the corresponding member's of baseline spectrum data group ratio, or logarithmic function. In relevant embodiment, if each member of spectrum data group after the calibration has the numerical value that differs the amount of being higher than D, so just think that they have the biology conspicuousness, D=F (1.1)-F (.9) wherein, and F is quadratic function. In this embodiment, first site that quantitatively all is positioned at of the acquisition of first sample and first spectrum data group is located, enter the spectrum data group that the database that is stored in second position in the digital storage media produces calibration by network, wherein database is renewable to reflect quantitative first spectrum data group from sample. In addition, use network to comprise and enter global computer internet.

In relevant embodiment, quantified measures is definite by increasing, and requiring measuring condition is that the amplification efficient of all components differs less than about 2 percentage points, perhaps less than about 1 percentage point.

Also have another embodiment to be based on the method that certain index is provided from first sample of experimenter, this index is the indication that the experimenter suffers from infectious disease or the relevant inflammation of infectious disease, described first sample provides the RNA source, described method comprises from spectrum data group of first sample acquisition, this spectrum data group comprises a plurality of members, each member is the measured value of certain distinct rna group component in one group of selected component, thereby the measured value that makes these components becomes the indication of the doubtful symptom of general infection, and described group comprises at least two kinds of components in the gene expression group in the table 1. In the process that derives described spectrum data group, described each component detects repeatably to be finished under the condition basically, at least one measured value from the spectrum data group is applied in the target function, this function provides from the mapping (mapping) to a measured value of the doubtful symptom of general infection of at least one measured value of described spectrum data group, thereby has produced and experimenter's infectious disease or the index of the relevant inflammation-related of infectious disease.

In addition, the experimenter can have the doubtful symptom of general infection, at least comprise one of following symptom: namely with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction, perhaps, infectious disease or inflammation may relate to by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics and checking or the inflammation that causes of at least a reason wherein such as treatment.

In relevant embodiment, target function is built into every linear summation, and form is: $I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)}$ Wherein I is index, M_iThe value of spectrum data group membership i, C_iBe constant, P (i) is M_iThe power that raises, summation are that all integer value additions of i form, and i can reach the number of member in the data group. In addition, use such as statistical methods such as latent class models and determine C_iRelevant with given data with P (i) value, comprise clinical, test and originate and any other data relevant with the doubtful symptom of general infection. In alternate embodiment, the standardized value of target function is provided, it is measured with respect to relevant group of experimenter, thereby index can be described with respect to standardized value, wherein standardized value can comprise that thereby making up target function makes standardized value be approximately 1, thereby perhaps make standardized value be approximately 0, and the deviation chart since 0 target function is shown standard deviation units. In other embodiments, relevant group of the experimenter has following at least a denominator: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, body movement, body weight and environmental exposure, perhaps optionally have following at least a denominator: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed body movement, body weight and environmental exposure.

In other embodiments, clinical indication can be used for assessing by the spectrum data group explain calibration in the background of at least a other clinical indication after infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group, and wherein at least a other clinical indication is selected from blood chemistry, urinalysis, X ray or other radiation or metabolic imaging technology, other chemical assay and physical examination. In addition, quantitative measurment can be determined by amplification, measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points, perhaps they differ less than 1 percentage point, basically repeatably measuring condition is within being better than 5 percentage points repeated scope, or is better than in 3 percentage points the repeated scope.

In this embodiment, the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, and first sample is from the tissue that is different from described local organization type or fluid, the relevant inflammation of infectious disease wherein or infectious disease infects from microorganism, more specifically being that bacterium infects, also more specifically is eucaryon parasitic infection, virus infections, fungal infection or from systemic inflammatory response syndrome (SIRS).

87. the method according to the index of claim 61 is provided, further comprises:

From at least a other sample, derive at least one other spectrum data group, described at least a other spectrum data group comprises a plurality of members, each member is the quantitative assay value of distinct rna group component in one group of selected component, thereby makes the measured value of component become the indication of the doubtful symptom of general infection;

The other sample of wherein at least one is from same experimenter, extracts being different from regard to one of following factor at least under the circumstances that first sample extracts: time, nutrition history, medical situation, clinical indication, medicine processing, body movement, body weight and environmental exposure situation; With

To be applied in the target function from least one measured value of at least one other spectrum data group, at least one measured value that described target function is provided at described at least one other spectrum data group under the different situations is to the mapping of a measured value of infectious disease or the relevant inflammation of infectious disease, thereby is created in the situation that is different from first sample and experimenter's infectious disease or at least one other index of the relevant inflammation-related of infectious disease.

Relevant embodiment comprises provides index, and target function wherein has 2,3,4 or 5 compositions, comprises the seriousness of disease condition, disease or the process of morbidity. In addition, target function is built into every linear summation, and form is: $I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)}$ Wherein I is index, M_iThe value of spectrum data group membership i, C_iBe constant, P (i) is M_iThe power that raises, summation are that all integer value additions of i form, and i can reach the number for member in the data group. In addition, use such as statistical methods such as latent class models and determine C_iRelevant with given data with P (i) value, comprise clinical, test and originate and any other data relevant with the doubtful symptom of general infection.

Perhaps, the standardized value of target function is provided, relevant group of mensuration of carrying out with respect to the experimenter, thereby at least a other index can be described with respect to standardized value, the standardized value that wherein provides comprises that thereby making up target function makes standardized value be approximately 1, thereby perhaps make standardized value be approximately 0, and the deviation chart since 0 is shown standard deviation units in the target function. Described embodiment also can comprise with clinical indication assesses infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group by the spectrum data group explain calibration in the background of at least a other clinical indication after, and wherein at least a other clinical indication is selected from blood chemistry, urinalysis, X ray or other radiation or metabolic imaging technology, other chemical assay and physical examination.

As in other embodiments, quantitative measurment can be determined by amplification, measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points, perhaps they differ less than 1 percentage point, basically repeatably measuring condition is within being better than 5 percentage points repeated scope, or is better than in 3 percentage points the repeated scope.

In addition, the relevant inflammation of infectious disease or infectious disease is with regard to experimenter's local organization, and first sample is from the tissue that is different from described local organization type or fluid.

Also have other embodiment to comprise be used to the method that index is provided, the relevant inflammation of infectious disease wherein or infectious disease infects from microorganism, more specifically being that bacterium infects, also more specifically is at least two kinds of components that comprise in eucaryon parasitic infection, virus infections, fungal infection or the group from systemic inflammatory response syndrome (SIRS) and component in the table 1.

Another embodiment provides based on assess experimenter's infectious disease or the method for the relevant inflammation of infectious disease from first sample of experimenter, described first sample provides the RNA source, described method comprises from first sample and obtains first spectrum data group, described first spectrum data group comprises a plurality of members, each member is the quantitative assay value of the amount of certain distinct rna component in one group of selected component, thereby can assess infectious disease or the relevant inflammation of infectious disease by the measured value of these components, wherein each component detects and basically repeatably finishes under the measuring condition. The method comprises that also generation is for the spectrum data group after the calibration of this group, wherein calibrate the function that each member of spectrum data group is the corresponding member of first spectrum data group and this corresponding member of group baseline spectrum data group, wherein each member of baseline spectrum data group is the standardization measured value of the amount of one of component in the group of mensuration with regard to relevant group experimenter, and described baseline spectrum data group is corresponding with infectious disease to be assessed or the relevant inflammation of infectious disease, and the spectrum data group of calibrating is the comparison between first spectrum data group and the baseline spectrum data group, thereby can assess experimenter's infectious disease or the relevant inflammation of infectious disease.

In this embodiment, the experimenter can have the doubtful symptom of general infection, at least comprise one of following symptom: namely with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction, perhaps, infectious disease or inflammation may relate to by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics and checking or the inflammation that causes of at least a reason wherein such as treatment.

In addition, relevant group of the experimenter is the health volunteer's group with one of following common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed body movement, body weight and environmental exposure. As in other embodiments, quantitative measurment can be determined by amplification, measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points, perhaps they differ less than 1 percentage point, and measuring condition is within being better than 5 percentage points repeated scope or to be better than in 3 percentage points the repeated scope be basically repeatably.

In this embodiment, the relevant inflammation of evaluated infectious disease or infectious disease is for experimenter's local organization, first sample comes from tissue or the fluid that is different from described local organization type, and the spectrum data group can be stored in the digital storage media, comprises it is stored in the database as record. In addition, baseline spectrum data group is being different from one or more other samples that obtain under first sample sampling condition from same experimenter, wherein one or more other samples obtain before treatment is intervened or after the treatment intervention, perhaps one or more other samples obtain in certain time interval, this time interval is initial sample and at least one moon of this sample sampling interval, and perhaps the interval is at least 12 months. In addition, if first sample come autoblood then baseline spectrum data group come experimenter's tissue fluid or body fluid outside the autoblood, perhaps, first sample is from experimenter's tissue fluid or body fluid, then baseline spectrum data group is come autoblood.

Also have another embodiment that infectious disease or the infectious disease relevant inflammation of a kind of method in order to assess the experimenter is provided, the method take from first sample of experimenter and from second sample of the indicator cells group who determines as the basis, described sample provides the RNA source, and the method comprises first sample or its part are added on definite indicator cells group. Described method also comprises by second sample derives first spectrum data group, first spectrum data group comprises a plurality of members, each member is the quantified measures of certain distinct rna or protein component amount in one group of selected component, thereby can weigh the doubtful symptom of general infection by the detection of these components, wherein the described measured value for each component is repeatably obtaining under the measuring condition basically, described method also comprises the spectrum data group that produces for the calibration of this group, each member of the spectrum data group that its alignment is crossed is the corresponding member of first spectrum data group and function for the corresponding member of baseline spectrum data group of this group, wherein each member of baseline spectrum data group measures the standardization measured value that obtains to the amount of one of component described in this group, and wherein baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed, the spectrum data group of calibrating is the comparison between first spectrum data group and the baseline spectrum data group, thereby can assess experimenter's infectious disease or the relevant inflammation of infectious disease.

In relevant embodiment, the experimenter can have the doubtful symptom of the general infection that comprises at least one of following symptom, namely, with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated, blood pressure raises or reduction, perhaps, infectious disease or inflammation may relate to by blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics and checking or the inflammation that causes of at least a reason wherein such as treatment, and relevant group of experimenter is one group of health volunteer.

In addition, relative group of the experimenter is the health volunteer's group with one of following common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed body movement, body weight and environmental exposure. In addition, clinical indication can be used to assess infectious disease or the relevant inflammation of infectious disease that relevant experimenter organizes by explain the spectrum data group after the calibration in the background of another kind of at least clinical indication, and wherein at least a other clinical indication is selected from blood chemistry, urinalysis, X ray or other radiation or metabolic imaging technology, other chemical assay and physical examination.

For other embodiments, quantitative measurment can be determined by amplification, measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points, perhaps they differ less than 1 percentage point, and measuring condition is within being better than 5 percentage points repeated scope or to be better than in 3 percentage points the repeated scope be basically repeatably. In addition, evaluated infectious disease is with regard to experimenter's local organization, and first sample is from the tissue that is different from described local organization type or fluid, and infectious disease or the relevant inflammation of infectious disease are that microorganism infects.

In relevant embodiment, baseline spectrum data group is being different from one or more other samples that obtain under first sample sampling condition from same experimenter, wherein one or more other samples obtain before treatment is intervened or after the treatment intervention, or in certain time interval, obtain, the described time interval is initial sample and at least one moon of this sample sample interval, and perhaps the interval is at least 12 months. In this embodiment, if first sample come autoblood then baseline spectrum data group come experimenter's tissue fluid or body fluid outside the autoblood, perhaps, first sample is from experimenter's tissue fluid or body fluid, then baseline spectrum data group is come autoblood.

In another embodiment of the present invention, provide to be subjected to the target cell group's that described the first reagent affects infectious disease or the relevant inflammation of infectious disease from the target cell group's who has used the first reagent sample as the basis assessment, described sample provides the RNA source. Described method comprises derives first spectrum data group from sample, first spectrum data group comprises a plurality of members, each member is the quantified measures of certain distinct rna group component in one group of selected component, thereby can assess infectious disease or the relevant inflammation of infectious disease that affected by described the first reagent by the detection of these components, wherein the described measured value for each component is repeatably obtaining under the measuring condition basically, described method has also produced the spectrum data group for the calibration of this group, each member of the spectrum data group that its alignment is crossed is the corresponding member of first spectrum data group and function for the corresponding member of baseline spectrum data group of this group, wherein each member of baseline spectrum data group measures the standardization measured value that obtains relevant group target cell group to the amount of one of component described in this group, and wherein baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed, the spectrum data group of calibrating is the comparison between first spectrum data group and the baseline spectrum data group, thereby can assess infectious disease or the relevant inflammation of infectious disease that is subjected to the target cell group that the first reagent affects. The target cell group can have the doubtful symptom of the system's infection that comprises at least one of following symptom, that is, with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated, blood pressure raises or reduction. Infectious disease or inflammation may relate to by at least a inflammation that causes in blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or the reasons such as gynemetrics's inspection or treatment. Relevant group of the target cell group can be the target cell group of one group of health. Perhaps, relevant group of the target cell group can have one of following common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed body movement, body weight and environmental exposure. In said case, clinical indication can be used for assessing relevant target cell group's infectious disease or the relevant inflammation of infectious disease, and the method further is included at least a other clinical indication background and explains the spectrum data group of calibrating, the described at least a other optional autoblood chemistry of clinical indication, urinalysis, X ray or other radiation or metabolic imaging technology, other chemical assay and physical examination. Quantitative measurment can determine that measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points by amplification, and perhaps they differ less than 1 percentage point. Measuring condition is within being better than 5 percentage points repeated scope or to be better than in 3 percentage points the repeated scope be basically repeatably. In addition, evaluated infectious disease or the inflammation relevant with infectious disease are with regard to experimenter's local organization, and first sample is from the tissue that significantly is different from described local organization type or fluid. The relevant inflammation of infectious disease or infectious disease may be microorganism infection, bacterium infection, eucaryon parasitic infection, virus infections, fungal infection, systemic inflammatory response syndrome (SIRS), bacteremia, viremia virusemia, fungemia or the septicaemia that caused by the microorganism of any classification. The relevant embodiment of described method can comprise that also storage spectrum data group is in digital storage media. Storage spectrum data group can comprise it is kept in the database as record. This embodiment can comprise that restriction is that first sample comes autoblood and baseline spectrum data group to come experimenter's tissue fluid or body fluid outside the autoblood. Perhaps, first sample is from experimenter's tissue fluid or body fluid, and baseline spectrum data group is come autoblood. Equally, baseline spectrum data group can be different from one or more other samples that obtain under first sample sampling condition from same experimenter. One or more other samples like this obtain before treatment is intervened or after the treatment intervention, or after certain time interval, obtain, at least one moon of initial sample and this sample sampling interval.

Other embodiment of the present invention relates to respect to the target cell group's who affected by the second reagent infectious disease or the relevant inflammation of infectious disease for assessment, be subjected to the target cell group's that the first reagent affects infectious disease or the method for the relevant inflammation of infectious disease, it take from first sample of the target cell group who has used the first reagent and from second sample of the target cell group who has used the second reagent as the basis, described sample provides the RNA source. The step that such method comprises has, derive first spectrum data group from first sample, derive second spectrum data group from second sample, first and second spectrum data groups comprise a plurality of members separately, each member is the quantified measures of a distinct rna group component in one group of selected component, thereby can assess with respect to the second reagent by the detection of these components, the infectious disease or the relevant inflammation of infectious disease that affected by described the first reagent, wherein the described measured value for each component is repeatably obtaining under the measuring condition basically, described method has also produced for this and has organized first spectrum data group of calibrating and second spectrum data group of calibrating, wherein each member of (i) first spectrum data group of calibrating is the corresponding member of first spectrum data group and function for the corresponding member of baseline spectrum data group of this group, and (ii) each member of second spectrum data group of calibrating is corresponding member and the corresponding member's of baseline spectrum data group of second spectrum data group function, wherein each member of baseline spectrum data group measures with respect to relevant group experimenter, the standardization measured value of the amount of one of component described in this group, and wherein baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed, first and second spectrum data group of calibrating are comparison between first spectrum data group and the baseline spectrum data group and the comparison between second spectrum data group and the baseline spectrum data group, thereby can assess infectious disease or the relevant inflammation of infectious disease with respect to the target cell group of the second reagent impact, be subjected to the target cell group's that the first reagent affects infectious disease or the relevant inflammation of infectious disease. The target cell group can have the doubtful symptom of the system's infection that comprises at least one of following symptom, that is, with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated, blood pressure raises or reduction. Equally, the target cell group may have the doubtful symptom that relates to by at least a systemic infection that causes inflammation in blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or the reasons such as gynemetrics's inspection or treatment. The first reagent can be the first medicine and the second reagent can be the second medicine. Perhaps, the first reagent is a kind of medicine and the second reagent is a kind of compound mixture or nutrient drug. Quantitative measurment can determine that measuring condition is that the amplification efficient of all components is differed less than about 2 percentage points by amplification, and perhaps they differ less than 1 percentage point. Measuring condition is within being better than 5 percentage points repeated scope or to be better than in 3 percentage points the repeated scope be basically repeatably. The relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, and first sample is from the tissue that is different from described local organization type or fluid. The relevant inflammation of infectious disease or infectious disease may be microorganism infection, bacterium infection, eucaryon parasitic infection, virus infections, fungal infection, systemic inflammatory response syndrome (SIRS), bacteremia, viremia virusemia, fungemia or the septicaemia that caused by the microorganism of any classification. Described method also can comprise stores first and the step of second spectrum data group in digital storage media. Storing first and second spectrum data group can comprise it is kept in the database as record. Baseline spectrum data group can be different from first sample sampling condition or be different from one or more other samples that obtain under second sample sampling condition from same experimenter. First sample comes autoblood and baseline spectrum data group is come experimenter's tissue fluid or the body fluid outside the autoblood. Perhaps, first sample is from experimenter's tissue fluid or body fluid, and baseline spectrum data group is come autoblood.

In another embodiment of the present invention, provide index as the experimenter's inflammation indication with the doubtful symptom of general infection as the basis take first sample from the experimenter, described first sample provides the RNA source. Described method comprises from spectrum data group of first sample acquisition, this spectrum data group comprises a plurality of members, each member is the measured value of certain distinct rna group component in one group of selected component, thereby the measured value that makes these components becomes the indication of inflammation, described group comprises at least two kinds of components in the gene expression group in the table 1, in the process that derives described spectrum data group, described each component measured value is repeatably obtaining under the condition basically, at least one measured value from the spectrum data group is applied in the target function, this function provides from the mapping to a measured value of described inflammation of at least one measured value of described spectrum data group, thereby produced the index with the inflammation-related of sample, wherein target function has used from the data for the baseline spectrum data group of this group, each member of baseline spectrum data group is that base-line data group wherein relates to inflammation to be assessed with respect to the standardization measured value of the amount of one of component described in this group of relevant group experimenter mensuration. The experimenter can have the doubtful symptom of the general infection that comprises at least one of following symptom, that is, with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated, blood pressure raises or reduction. Perhaps, the doubtful symptom of general infection relates to by at least a caused inflammation in blunt wound or penetrability wound, operation, endocarditis, urinary tract infections, pneumonia or dentistry or the reasons such as gynemetrics's inspection or treatment. Measured value in described at least one spectrum data group that is applied in the target function may be 2,3,4 or 5.

Also have other embodiment to provide with the index method that guiding treatment is intervened in infectious disease or the relevant inflammation patient of infectious disease, the index that provides according to arbitrary in the above-mentioned embodiment is provided the method, this index is compared to obtain difference value with this index of gained of standardized value measure to(for) relevant experimenter's group, then come the guiding treatment intervention with the difference between described index and this index standardized value, treatment intervention wherein is the microorganism specific treatment, or bacterium specific treatment, or fungi specific treatment, or virus-specific treatment, or eucaryon parasite specific treatment.

Another embodiment provides the method that is used for pathogen type in one group of purpose pathogen is distinguished infectious disease or the relevant inflammation patient of infectious disease, take at least one from experimenter's sample as the basis, this sample provides the source of RNA, described method comprises at least one spectrum data group of measuring for the experimenter, with this spectrum data group with at least one group of relevant group of sample in the purpose kind pathogen measured at least one the baseline spectrum data group that obtains compare to obtain difference value, with distinguishing for the pathogen type at least one spectrum data group of experimenter the Pathogen category of this difference value at least one group of baseline spectrum data group, wherein said Pathogen category is microorganism. Perhaps, the kind of pathogen is bacterium, and this difference value is used for gram-positive bacterium pathogen and gramnegative bacterium pathogen are made a distinction. Perhaps, the kind of pathogen is fungi, and then described difference value is used for distinguishing Mycotoruloides (Candida) pathogen and chronic Mycotoruloides pathogen. More particularly, the kind of pathogen is virus, then this difference value is used for distinguishing dna virus pathogen and RNA viral pathogen, perhaps the kind of pathogen is virus, and described difference is used for distinguishing Rhinovirus (rhinovirus) pathogen and Influenza Virus (influenza) pathogen. Also more particularly, this Pathogen category is the eucaryon parasite, and then described difference is used for distinguishing Plasmodium (plasmodium) parasitic disease substance and Trypanosomonas (trypanosomal) pathogen.

Also have another embodiment to provide and utilize index from one group of purpose pathogen, to distinguish the method for pathogen type in infectious disease or the relevant inflammation patient of infectious disease, take at least one from experimenter's sample as the basis, described method comprise provide according in the above-mentioned embodiment any at least one index of experimenter, at least one index is compared to obtain at least one difference value with this index of gained of at least one standardized value measure to(for) at least one group of relevant experimenter group, then utilize at least one difference value between at least one standardized value of described at least one index and this index from a class pathogen, to distinguish the type of pathogen.

The accompanying drawing summary

Aforesaid feature of the present invention will be easier to understand with reference to following detailed description and accompanying drawing thereof, wherein:

Figure 1A has shown during single male sex experimenter suffers from the optic neuritis process and to have detected at 8 days respectively from the result of 24 genes of inflammatory genome (shown in the table 1) originally.

1B has set forth the application of the inflammatory parameters that relates to Figure 1A data according to embodiment of the present invention.

Fig. 2 is the diagram of the identical inflammatory parameters that calculates in 9 different important clinical critical events.

Fig. 3 has shown the effect of the single dose 800mg brufen processing that characterizes by described index in single donor.

Fig. 4 has illustrated the calculating acute inflammation index of illustrated five different situations.

Fig. 5 has shown the viral indicator reaction that is used for the monitoring infection of the upper respiratory tract (URI) process.

Fig. 6 has compared two kinds of different colonies (48 sites that relate to table 1 inflammation gene expression expression group) with 7 usefulness gene expression atlas.

Fig. 8 compares normal colony and rheumatoid arthritis colony from the longitudinal research direction.

Fig. 9 has compared two kinds of normal colonies, and is a kind of vertical, a kind of horizontal.

Figure 10 has illustrated the gene expression value that demonstrates for a plurality of individualities in the normal colony.

Figure 11 has shown the expression of each gene in 4 genes (table 1 inflammation gene expression expression group), 8 every months in the middle of the month single experimenter is detected.

The expression of each in Figure 12 and 13 similar 48 genes that shown in each situation unique separately experimenter (in each situation to feel good and do not take medicine as the basis and select) (in the table 1 inflammation gene expression expression group), measuring weekly lasting 4 weeks in the situation of Figure 12, is to measure per month to continue 6 months in the situation of Figure 13.

Figure 14 shown and used within a certain period of time the impact that the anti-inflammatory steroids is expressed inflammation gene expression among the single people experimenter, detects with the inflammation gene expression expression group of table 1.

Figure 15 uses the single dose metacortandracin to the impact of 5 genes (in the inflammation gene expression expression group of table 1) expression within a certain period of time to have shown by the whole blood sample available from people experimenter with the similar mode of Figure 14.

Figure 16 has also shown and has used within a certain period of time the impact that TNF inhibition compound is expressed inflammation gene expression among the single rheumatoid arthritis patient, but expression described herein is represented as the comparison of carrying out with the average level at normal (that is, not yet diagnosed, healthy) similar position of colony of measuring in advance (with Fig. 6 and 7 relevant).

Figure 17 A has further described the uniformity that inflammation gene expression is expressed in colony.

Figure 17 B has shown the normal distribution available from the desired value of not making a definite diagnosis colony.

Figure 17 C has illustrated the application of the index identical with Figure 17 B, and wherein the inflammation intermediate value of normal colony is set as 0, and normal and ill experimenter is carried out mapping with respect to the standard deviation units of this intermediate value.

Figure 18 made in the mode that is similar to Figure 17 A two groups different (reactor is to nonresponders) the trouble rheumatoid arthritis experimenter colony (every group of 6 people) with Figure 17 A in the gene expression atlas in identical 7 sites.

Figure 19 illustrates the application of inflammation index in the single experimenter of assessment trouble rheumatoid arthritis thus, and described experimenter is to traditional methotrexate (MTX) therapy poor response.

Figure 20 is similar to have described the application of described inflammation index in 3 rheumatoid arthritis patients of assessment, and described patient is to traditional methotrexate (MTX) therapy poor response.

Figure 21-23 has shown respectively and has experienced three kinds of independently inflammation indexs of international category rheumatic arthritis patient after the therapy.

Figure 24 has described the inflammation index to assessing single inflammatory bowel disease patient's application.

Figure 25 shown with reference to other NSAIDs (NSAIDs), the gene expression atlas of 24 sites of the whole blood of processing at the external use brufen (in the inflammation gene expression expression group of table 1).

That Figure 26 has shown is how objective, quantitative, two kinds of competitive anti-inflammatory function of chemical compounds relatively accurately and repeatably.

Figure 27 to 41 has illustrated the application of gene expression group in the early stage evaluation of infectious disease and monitoring.

Figure 27 utilizes the new bacteria gene expression group of 24 genes of research and development to distinguish different bacterium situation in the host living beings system.

Figure 28 has shown from three kinds of independent sources: the LTA of streptococcus pyogenes (S.pyogenes), bacillus subtilis (B.subtilis) and golden streptococcus (S.aureus) is at the differential expression of Single locus IFNG.

Figure 29 and 30 shown respectively in the whole blood inflammation 48A and 48B site (relating separately to above-mentioned Fig. 6 and 7) after two hours to applying the reaction of Gram-positive and gram-negative biological.

Figure 31 with 32 respectively corresponding to Figure 29 and 30 and similar to them, except monitoring is herein carried out after using 6 hours.

Figure 33 has compared the gene expression reaction of being brought out and being brought out by the Escherichia coli filter liquor of inanimate object body by Escherichia coli.

Figure 34 and Figure 33 are similar, but the reaction relatively of this place is to the reaction from the stimulation of the stimulation of independent Escherichia coli filter liquor and the Escherichia coli filter liquor that adds PB to controlling oneself.

Figure 35 has described the gene expression reaction of bringing out after golden streptococcus adds 2,6 and 24 hours.

Figure 36 to 41 compared variable concentrations and the time Escherichia coli and the gene expression brought out of golden streptococcus.

Figure 42 has described statistics T has been detected the potential member who is applied to differentiate the signal gene expression group that can distinguish between normal subjects and the unstable rheumatoid arthritis patient.

Figure 43 has described the expression of 8 bacteremic patients of doubtful trouble for the group of 17 genes.

Figure 44 has described statistics T has been detected the effective member who is applied to differentiate the signal gene expression group that can distinguish between normal subjects and the bacteremia patient.

Figure 45 has described the application of an algorithm (as shown in FIG.), has obtained the index of correlation of the rheumatoid arthritis (RA) when being applied to respectively normal subjects, rheumatoid arthritis patient and bacteremia patient.

Figure 46 has described the application of an algorithm (as shown in FIG.), has obtained the bacteremia index of correlation when being applied to respectively normal subjects, rheumatoid arthritis patient and bacteremia patient.

The detailed description of particular implementation scheme

Definition

Unless other needs are arranged in the context, otherwise following term should have hereinafter pointed implication:

" algorithm " is a rule for the descriptive biology situation. Described rule can be special definition on the algebraically, also can comprise alternative or a plurality of decision-points of the special domain knowledge of needs, professional explanation or other clinical indication.

According to defined other term herein, " reagent " is " composition " or " stimulus ", or the combination of composition and stimulus.

" amplification " is the function of dna replication dna number in the quantitative RT-PCR test, can carry out quantitatively its concentration thus. " amplification " is in sensitivity and the specificity of this specified amount detection technique. Therefore, amplification is the measured value that component concentration is provided under amplification efficient and resultant sensitivity for all components that detects and repeated basically similar condition.

" baseline spectrum data group " be be used for the expection biology situation of arithmetic standardization purpose under biology sample (or colony and a sample) is assessed a relevant numerical value of the gene expression group component that produces. The biology condition of expection can be, for example, before being exposed to certain reagent or do not treating that disease exists or not ill condition under experimenter's (or colony or one group of experimenter) situation. Alternatively, or additional, the biology situation of expection can be experimenter or colony or one group of experimenter's health status. Alternatively, or additional, the biology situation of expection can be and organize relevant situation based on one of following factor selected colony or experimenter: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

One " group " or " group " sample or experimenter refer to limit or selected sample or experimenter's group, have basic general character or association between the member who wherein comprises in this group or this group sample or experimenter.

One " cell mass " refers to any cell group, wherein exists basic general character with related between the member of cell mass, for example, comprises that one group of cell is from an organism or from a collection of cultured cell or from tissue biopsy's sample.

Experimenter's " biology situation " is the experimenter's situation that is in relevant field under the observation, described field may comprise any aspect that can monitor the experimenter that its situation changes, such as health status, the disease that comprises cancer, wound, aging, infection, tissue degeneration, developmental process, healthy, obesity and mood. As observable, the situation in this scope may be chronic or acute or only be instantaneous. In addition, the biology situation of target can show by organism or cell mass maybe can be confined to (such as skin, heart, eyes or blood) in the specific organ, but in either case, described situation all can be by the cell mass that is affected a sample and directly monitored, or carry out indirect monitoring by the sample from other position of experimenter. Term " biology situation " comprises " physiology situation ".

Experimenter's " body fluid " comprises blood, urine, spinal fluid, lymph liquid, mucous membrane juice, prostatic fluid, seminal fluid, hemolymph or other any body fluid known in the art of experimenter.

" the spectrum data group of calibration " is for first spectrum data group membership of given component and the corresponding member's of baseline spectrum data group function in the group.

" clinical indication " is to be combined any physiological data for assessment of cell mass or organism physiology situation separately or with other data. This term comprises clinical front indication.

" composition " comprises the complex mixture of the combination, toxin, food, food additives, mineral and the material that are in any physical state or chemical compound, nutrient drug in the physical state situation of combination, medicine, homeotherapy preparation, confrontation therapy preparation, naturopathy preparation, compound.

" derivation " spectrum data group comprises by following dual mode and measures the one group numerical value relevant with the component of gene expression group from sample: (i) by direct detection of biological imitate in the product described component or (ii) be exposed in the primary sample by detection or derived from described component in the second biology sample in the material of primary sample.

" unique RNA or protein component " in one group of component is unique gene outcome of expressing, perhaps RNA or protein. " expression " product of gene comprises the gene outcome by the translation generation of mRNA, or RNA or protein.

" gene expression group (gene expression panel) " is one group of component examining through experiment, each component is the unique product of expressing of gene, or be RNA or for protein, wherein the selection of this group component is can detect target organism situation by their detection.

" gene expression atlas " is the one group numerical value relevant with gene expression group component that is produced by assessment biology sample (sample group or sample group).

" gene expression atlas inflammatory parameters " provided the situation of gene expression atlas to the value of the target function of the mapping of monodrome inflammation measured value.

Experimenter's " health status " comprises experimenter's intelligence, mood, health, spirit, confrontation therapy, naturopathy and hahnemannian situation.

" index " is in order to help to simplify or to show or inform more complicated quantity information analysis and the arithmetic that carries out or the numerical characteristic of mathematical derivation. The index of disease or colony can be determined for several experimenters or sample with common biology state by using specific algorithm.

The meaning that " inflammation " is used for herein is the same with the general medical science meaning of this word, and can be reaction acute or chronic, simple or pyogenic, local or that scatter, cell or tissue, cause or keep by any amount of chemistry, physics or biological reagent or reagent combination.

" inflammatory state " is used in reference to the corresponding biology situation of experimenter that is produced by inflammation, and perhaps the degree by inflammation characterizes it.

The number that refers to the data group based on " the large quantity " of the data group of the common group of gene is even as big as obtaining with respect to take the same group of significance,statistical result for the routine data group on basis.

Experimenter's state before " standard " state of the experimenter of composition to be administered refers to use also can even the experimenter is ill by chance.

Gene " group " is the one group of gene that comprises at least two components.

Can comprise the individual cells of taking from the experimenter or the aliquot of a plurality of cell or cell fragment or body fluid from experimenter's " sample ", used mode comprises venipuncture, drainage, ejaculation, massage, slicer, syringe needle absorption, lavation sampling, scraping, operation incision or intervention or alternate manner known in the art.

" characteristic spectrum (signature profile) " is through the subset of experiment confirm in the gene expression atlas of selecting for the physiology mechanism of distinguishing biology state, reagent or effect.

" feature group " is the subset of gene expression group, and the selection of its component is in order to distinguish the physiology mechanism of biology state, reagent or effect.

" experimenter " is cell, tissue or people or the non-human being's body that is under observing, and no matter is in the body, that exsomatize or external. When we mention based on from experimenter's sample assessment experimenter's biology situation the time, not only comprised being used to organize sample to assess people experimenter's situation from people experimenter's blood or other, also comprised and used blood sample itself to assess therapy for example or certain reagent to the effect of this sample as tested product.

" stimulation " comprises that (i) physics monitored and experimenter interacts, for example ultraviolet light,long wave or B, or for the light therapy of seasonal emotional maladjustment, perhaps treat melanoma with psoralen treatment psoriasis or with the radioactive substance of implanting, other radiation exposure, and (ii) experimenter's any monitored health, intelligence, mood or spiritual activity or inactive property.

" treatment " comprises all interventions that are intended to keep or change the monitored biology situation of experimenter, no matter is biological, chemical, physics, preternatural method or the combination of these preceding methods.

The patent application that is hereby expressly incorporated by reference, this paper inventor proposes and the PCT Patent Application Publication WO01/25473 that announces, is entitled as " system and the method for learning state or reagent with the gene expression atlas characterising biological of calibration " in April 12 calendar year 2001 have announced the application of gene expression group in following assessment: (i) biology state (comprising health and disease) and (ii) one or more reagent on the impact (comprising health status, toxicity, therapeutic agent processing and drug effect) of biology state.

Especially, the gene expression group can be used for detecting therapeutic efficiency natural or synthetic composition or stimulus, and they can learn state separately preparation or combination or mixing for the target organism of certain limit; The mixture of expection composition or composition is renderd a service toxicological action and the dosage of certain individuality or a group or one group of individuality or a group cell, thereby determining how two or more different reagent of using in single therapy may interact detects any synergy, increase, negative, neutral or poisonous activity, carry out clinical before or clinical testing so that experimenter that disease condition carries out according to informationalized spectrum data group is preselected to provide new standard in order to disclose, before carrying out the test of 1 phase and 2 phases, carry out the preparation dosetest for these patients. These gene expression groups can be used for sample from the experimenter to assess their biology state.

The selection mode of gene expression group is so that consisted of detection to experimenter's biology state by the quantitative detection of RNA or protein component in the group. In a kind of arrangement, used the spectrum data group of calibrating. Each member of the spectrum data group of calibrating is the measured value of unique ingredient in (i) gene expression group and (ii) function of baseline amount.

We have found under can the repetition condition (multiplicity of detection is better than 20%, and is preferred high 5 percentage points or higher, more preferably high 3 percentage points or higher) the quantitative detection of carrying out component can obtain valuable and unexpected result. For this purpose and following claim, we are higher than 20% with the multiplicity that detects and are used as the measuring condition that " basically can repeat " is provided. Particularly, wish to obtain each time the measured value corresponding to certain component expression in the concrete sample, should obtain substantially the same measured value for the expression of substantially the same level. In this way, gene expression group can significantly compare between sample and sample at the expression of certain component. Even for the expression measured value of certain concrete component be inaccurate (for example, for example, low by 30%), the standard of repeatability means for this component, depart from if having, to remain systematic departing from, and therefore the expression measured value of this component can carry out significant comparison. Can in the situation that changes, obtain valuable information and the correlated expression that compares component in this way.

Except the standard of repeatability, wish that also second standard also can satisfy, that is, basically carry out the quantitative detection of component under the condition of similar (in 1 to 2 percentage point, usually being less than 1 percentage point) in all components amplification efficient. When these two standards all were satisfied, the expression measured value of component can significantly compare with the expression measured value of another component or compare between sample in the given sample.

The present embodiment relates to certain index or algorithm application in the following areas, and described index and algorithm produce the quantitative detection from component, and can derive from addition analysis expert or calculation biology: (a) in the data component of complexity is analysed; (b) do not provide impact information or the small variation of other side between control or normalized sample or the experimenter in the gene expression value; (c) simplify the sign of complex data group in order to compare with other complex data group, database or from index or the algorithm of complex data group; (d) monitoring experimenter's biology state; (e) detection is learned situation and can be prepared individually or unite the natural or synthetic composition of preparation or the therapeutic efficiency of stimulus or mixture for the certain limit target organism; (f) estimate to render a service for toxicological action and the dosage of the mixture of the composition of individuality or a group or one group of individuality or cell mass or composition; (g) thus determining how two or more different reagent of using in single therapy may influence each other detects any synergy, increase, negative, neutral or poisonous activity; (h) carry out clinical before and clinical testing so that experimenter that disease condition carries out according to informationalized spectrum data group is preselected to be provided new standard and carried out preparation dose study for these patients before carrying out the test of 1 phase and 2 phases in order to disclose.

Gene expression atlas and for the application that concrete situation or reagent or the index of the two characterize can be used for reducing by 3 clinical trial phases expense and can be clinical in 3 phases outside use, for the medicine of approved marks, in a class medicine, select direct suitable medicine for its unique physiology situation for concrete patient, diagnosis or determine may be before paresthesia epilepsy the medical science illness or the prognosis of infection, or diagnosis is used relevant unfavorable negative interaction with certain therapeutic agent, the health care of body of managing patient, the quality of control different batches reagent or reagent mixture.

The experimenter

The method of herein announcing can be applicable to the cell of people, mammal or other organism and need not those of ordinary skills and carry out excessive experiment, because all cells transcribe rna and be known in the art how to extract RNA from all type cells all.

Select the component of gene expression group

Select the universal method of gene expression group component to consult PCT application publication number WO 01/25473. We designed and experiment confirm far-ranging a series of gene expression groups, each group provides the quantified measures of coming autoblood or other to organize the biology situation of sample. For each group, the gene expression atlas that experiment has confirmed to utilize the component of this group to obtain provides the information of biology situation, and (we have also proved in other article is providing in the biology situation information, the gene expression group also can be used for other side, and treatment is renderd a service and provide target for treating to intervene as detecting). The example of gene expression group and respectively the summary of component referring to following appended form:

Table 1. inflammation gene expression expression group

Table 2. diabetes gene expression group

Table 3. prostate gene expression group

Table 4. dermoreaction gene expression group

Table 5. liver metabolism and disease gene expression group

Table 6. endothelium gene expression group

Healthy and the natural death of cerebral cells gene expression group of table 7. cell

Table 8. cytokine gene expression group

Table 9.TNF/IL1 suppressor expression group

Table 10. chemokine gene expression group

Table 11. mastocarcinoma gene expression group

Table 12. infectious disease gene expression group

Other group can be made up and test and examine according to the application's relevant principle by those of ordinary skills.

The test design

We are usually with a sample quadruplicate experiment on group,, sample are divided into sample aliquot and for the concentration of each component in every a sample aliquot gene expression detection group that is. Altogether surpassed the test of 900 components, each test is quadruplicate carrying out, and we find that the average coefficient of variation (standard deviation/mean value) * 100 is less than 2 percentage points, usually less than 1 percentage point in the result of each test. This figure is the measured value of we so-called " variability between mensuration ". We test for different situations with the same sample material. By 72 tests, the component measurement of concetration value and the described measurement of concetration value that produce self-contained 24 members' group are to measure in three kinds of different situations, and we find the average coefficient of variation less than 5 percentage points, usually less than 2 percentage points. We are called so-called " variability between mensuration " with this.

We have found to utilize quadruplicate testing result to identify and the data point of eliminating statistics what is called " outlier " is significant, and described data point is to differ percentage greater than for example 3% and be not to produce by departing from greater than for example any system of 1% of the mean value of all four values. In addition, if there is more than one data point to get rid of by this step in one group of four value, all data for related component just all are removed so.

The gene expression of component detects in the group

For the amount of concrete RNA in the test sample, we used method known to persons of ordinary skill in the art extract and quantitatively in the sample transcribe rna of the component of related gene expression group (detailed flow process is as follows. Also can consult at this in conjunction with the PCT application publication number WO98/24935 as the reference of RNA analytical method). In brief, RNA extracts in the samples such as culture medium that may grow such as tissue, body fluid or experimenter's cell mass. For example, the cracking cell and in the solution that is suitable for carrying out the DNAse reaction eluted rna. Article one, the synthetic of chain can utilize reverse transcriptase to finish. Then can carry out gene magnification, the test of clearer and more definite quantitative PCR and (Hirayama etc., Blood 92,1998:46-52) for the size such as label alignment purpose genes such as 18S rRNA. At multiple double sample, test sample in 4 parts of repeat samples for example. Determine the relative quantity of mRNA by the difference in the limit cycle between internal control and the purpose gene. In embodiments of the invention, carry out quantitative PCR with amplification, report reagent with available from the equipment of Applied Biosystems (Foster City, CA). Obtained the purpose transcript amplification efficient determined, can be directly relevant with the amount of specific courier's transcript in the detected sample from the detectable point of the signal that is amplified To Template (such as, period). Similarly, such as fluorescence, enzyme work, per minute degradation rate, absorbance etc. other quantitatively signal with known To Template concentration (for example, the reference standard curve) relevant or because limited changeability and during by normalization, can be used for the number of To Template in the quantitative unknown sample for standard.

Although be not limited to the amplification method, the quantitate gene expression technology can be utilized the amplification of target transcript. Alternatively or with the amplification of target transcript unite, can also utilize the amplification of report signal. The amplification of To Template can be finished by isothermal gene magnification strategy or by thermal cycle gene magnifications such as PCR.

Wish to obtain between the target that is amplified or reporter gene and the starting template concentration definable and correlation repeatably. We notice that by careful also will test amplification efficient such as the ratio of constant primer-template is strict controlled in narrow can permission level interior (for example relative efficiency of 99.0-100%, the normally relative efficiency of 99.8-100%) can achieving the above object at discovery. For example, when measuring the gene expression dose of relevant term single gene expression map, must make group all components primer template ratio (for example, in 10 times scope) and amplification efficient (for example, less than 1%) remain in the limited scope of phase Sihe in order to can carry out accurately and the accurately relative determination of each component. Describe and the purpose of following claim for this, if amplification efficient differs and is no more than approximately 10%, we just think the efficient " basically similar " that increases. Preferred they differ should be less than about 2%, more preferably less than about 1%. In the whole to be detected concentration level scope relevant with corresponding biology situation, all should observe these constraintss. Therefore the various embodiments of this paper basically can repeat and wherein finish this standard under the measuring condition of the specificity of all components and the efficient basic simlarity that increases although must satisfy to detect, but, the result of the test that does not directly satisfy these criterions by calibration reaches described measuring condition also still in the desired scope of the invention of this paper, compensating error in this way, thus after suitable calibration testing result, satisfied described standard.

In practice, we test to guarantee that these conditions satisfy. For example, we design and make many primer-probes pair usually, and which right effect of measuring is best. Although namely use computer technology known in the art and general convention can improve design and the preparation of primer-probe, we find that still the affirmation of testing is very useful. In addition, in the process of experimental verification, we have linked together selected primer-probe combination with a series of characteristics.

Reverse primer should be complementary with the dna encoding chain. In one embodiment, introne-extron abutment should be crossed in the primer location, three of reverse primer causes end and is no more than 3 bases and near-end extron complementation (if the base that surpasses more than three is complementary, then can trend towards competitive amplification genomic DNA).

In embodiments of the invention, the primer probe should increase length less than the cDNA of 110 bases, and Ying Bucong is relevant but at biologically irrelevant locus amplification genomic DNA or transcript or cDNA.

The suitable target of selected primer probe is article one chain of cDNA, and in one embodiment, it should be prepared as follows:

(a) utilize whole blood to exsomatize and assess the biology state that affected by reagent.

Venipuncture obtains human blood and sample is divided into baseline, the non-stimulated thing of at least three time points and the q.s stimulus is arranged for experiment. Common stimulus comprises lipopolysaccharides (LPS), phytohemagglutinin (PHA) and hot deactivation staphylococcus (HKS) or carrageenan and can use individually (usually) or unite use. With the whole blood aliquot of heparinize mixed 37 ℃ of insulations 30 minutes that are incorporated in the air that contains 5%CO2 in the situation of non-stimulated thing. The stimulus that adds variable concentrations, mixed lower 37 ℃ of the ventilative situation of pipe cap that is incorporated in was placed 30 minutes. Can add other test compound and place the different time this moment, and this time is depended on the pharmacokinetics that institute's compound of surveying is expected. In the time of appointment, centrifugal collecting cell is removed blood plasma and is extracted RNA with various standard methods.

From cell mass to be tested or as purification of nucleic acid cell, tissue or the fluid of the clone of indicator, RNA and/or DNA. Preferably with various standard methods from mixtures of nucleic acids, obtain RNA (or RNA separation method RNA Isolation Strategies, the 55-104 page or leaf,The RNA methodology is separated With the lab guide RNA Methodologies that characterizes, A laboratory guide for isolation and characterization, second edition, 1998, Robert E.Farrell, Jr., Ed., Academic Press), what utilize at present is from Ambion (RNAqueous^TM, without the total RNA separating kit of phenol Phenol-free Total RNA Isolation Kit, Catalog #1912, version 9908; Austin, Texas) be filtered into the basis the RNA separation system.

According to a kind of method, carry out as follows for the whole blood test that gene expression atlas is measured: people's whole blood is extracted in the 10mL Vacutainer pipe that contains heparin sodium. To manage gentleness and put upside down mixed blood sample 4-5 time. This blood uses in 10-15 minute after splashing into. In experiment, blood is diluted 2 times, that is, every duplicate samples at each time point is 0.6mL whole blood+0.6mL stimulus. Prepare the solution that detects and add suitable stimulus.

Then the whole blood with a certain amount of (0.6mL) adds in the polypropylene test tube of each 12 * 75mm. The 2X LPS of adding 0.6mL in the LPS pipe (from e. coli serotype 0127:B8, Sigma#L3880 or serotype 055, Sigma#L4005,10ng/ml changes with different batches). Subsequently, in " contrast " pipe, add 0.6mL and detect liquid, two parts of samples that each situation is all prepared to repeat. Cap test tube is covered tightly. Put upside down test tube 2-3 time with biased sample. With pipe cap unclamp to the first lattice and with test tube at 37 ℃, 5%CO2 insulation 6 hours. In 6 hours, sample is mixed the haemocyte that suspends gently, from each pipe, take 1mL (with the micropipette rifle that has with the rifle head of baffle plate) away, and be transferred in " dolphin " microcentrifugal tube (Costar #3213) of 2mL.

Then with sample centrifugal 5 minutes of 500xg room temperature (IEC centrifuge or similar machine have the rotor that is fit to various microcentrifugal tubes), from each pipe, remove serum as much as possible and abandon it. Cell precipitation is placed on ice, with the fast as far as possible extraction RNA of Ambion RNAqueous kit.

(b) amplification strategy

With the special primer of information or the random primer special RNA that increases. The synthetic special primer of data according to available from public database (such as, Unigene, national bioengineering information centre, National Library of Medicine, Bethesda, MD) comprises the information available from genome and the cDNA library of people or other animal. Select the preferential amplification of primer from the special RNA of test group or indication group sample, consult, for example,The RNA methodology is about the lab guide RNA Methodologies that separates and characterize, A laboratory guide for isolation and characterizationThe 15th chapter, RT-PCR, second edition, 1998, Robert E.Farrell, Jr., Ed., Academic Press, orRNA separates and evaluation side Method RNA isolation and characterization protocolsThe 22nd chapter 143-151 page or leaf of one book, molecular biology method Methods in molecular biology, volume 86,1998, R.Rapley and D.L.Manning edit, Human Press, perhaps the statistics of primer design parameter improves the 14th chapter in Statistical refinement of primer design parameters one book, PCR uses: the 5th chapter 55-72 page or leaf that is used for the method PCR applications:protocols for functional genomics of functional genomics, M.A.Innis, D.H.Gelfand and J.J.Sninsky edit, 1999, Academic Press). Amplification under isothermy, carry out or with thermal cycler (for example, available from Applied Biosystems, Foster City, the ABI 9600 of CA or 9700 or 7700; Consult nucleic acid detection method Nucleic acid detection methods 1-24 page or leaf,Virus detects Molecular method Molecular methods for virus detectionIn one book, D.L.Wiedbrauk and D.H., Farkas edits, 1995, Academic Press) carry out. As described the same for amplimer, with identify and synthetic from given data storehouse openly and with the detection primer of fluorescence label detect the nucleic acid that is amplified (consult, for example, Taqman^TMPCR reaction kit, method, version A, numbering 402823,1996, Applied Biosystems, Foster City CA.). In this situation, use available from the ABI Prism 7700 Sequence Detection System detection of Applied Biosystems (Foster City, CA) and the DNA of quantitative amplification. That obtain with sample to be tested or available from the amount of the special RNA of indicating clone can with relevant (the consulting of viewed fluorescence relative quantity, for example, quantitative PCR technical progress: 5 ' nuclease check Advances in quantitative PCR technology:5 ' nuclease assays, Y.S.Lie and C.J.Petropolus, biotechnology general survey Current Opinion in Biotechnology, 1998,9:43-48, or quick thermal cycle and PCR dynamics Rapid thermal cyclin g and PCR kinetics, 211-229, PCR uses: the 14th chapter that is used for the method PCR applications:protocols for functional genomics of functional genomics, M.A.Innis, D.H.Gelfand and J.J.Sninsky edit, 1999, Academic Press).

As the concrete implementation to method described herein, we have described the method that synthetic article one cDNA chain is used for PCR in detail. The two all can use the method from the RNA of cultured cell (that is, THP-1 cell) with extraction for whole blood RNA.

Material

1.Applied Biosystems TAQMAN reverse transcription kit (P/N808-0234). Kit forms: 10X TaqMan reverse transcription buffer solution, the 25mM magnesium chloride, the deoxyNTP mixture, hexamer at random, the RNase inhibitor, MultiScribe reverse transcriptase (50U/mL) (2) is without RNase/Dnase water (DEPC from Ambion (P/N 9915G) processes water or coordinate).

Method

1. RNase inhibitor and MultiScribe reverse transcriptase are placed on ice immediately. But all other reagent room temperatures are thawed then to ice and are put.

2. melt from-80 ℃ of refrigerators taking-up RNA and room temperature, then place on ice immediately.

3. for every 100mL reverse transcription reaction, prepare following reverse transcriptase reagent mixture (for a plurality of samples, because the error of drawing need prepare the mixture of additional quantity):

1 reaction (mL) 11X is for example for 10 duplicate samples (mL)

10X RT Buffer 10.0    110.0

25mM MgCl2  22.0    242.0

dNTPs         20.0    220.0

Hexamers 5.0 55.0 at random

RNAse inhibitor 2.0 22.0

Reverse transcriptase 2.5 27.5

Water 18.5 203.5

Altogether: 80.0 880.0 (every duplicate samples 80mL)

4. with each RNA sample of cumulative volume 20mL (for example, for THP-1RNA, take out 10mL RNA and use without RNase/Dnase water and be diluted to 20mL, then use the total RNA of 20mL for whole blood RNA) put into the 1.5mL microcentrifugal tube and add from step 5,2,3 reverse transcriptase reaction mixture 80mL. Pressure-vaccum mixes up and down.

5. with sample room temperature insulation 10 minutes.

6. sample is incubated 1 hour at 37 ℃.

7. sample is incubated 10 minutes at 90 ℃.

8. sample is turned several circles fast in microcentrifuge.

9. just sample is placed on ice if carry out immediately PCR, otherwise sample is placed-20 ℃ for subsequent use.

10. all reverse transcription samples are being carried out all need calibrate (consulting SOP200-020) with 18S and beta-actin when electrophoresis is identified.

As follows with the situation with the primer probe gene expression detection group component of above-mentioned article one chain cDNA:

For setting up of the people's gene expression group of 24 genes of inflammation.

Material

1. for the 20X primer of each purpose gene/probe mixture.

2. for the 20X primer of the inherent object of reference of 18S/probe mixture.

3.2X the senior mixture of the general PCR of Taqman.

4. the cDNA that comes from the rna transcription of cell from extraction.

5.Applied Biosystems 96-hole light reaction is dull and stereotyped.

6.Applied Biosystems optics cap or optical transparency film.

7.Applied Biosystem Prism 7700 sequence detectors.

Method

1. be prepared as follows primer/probe of containing for the purpose gene, for the primer/probe of the inherent reference of 18S and each primer of the senior mixed liquor of 2x PCR/probe mixture storage liquid. Enough excessive errors in order to drawing that solution need be prepared, for example, about 10% is excessive. Following example has been described for certain gene and has been detected the usually system of preparation of two states (two flat boards) institute with the quarter sample.

1X (1 hole) 9X (being used for two flat boards)

2X Master Mix              12.50     112.50

20X 18S primer/probe mixture 1.25 11.25

20X purpose gene primer/probe mixture 1.25 11.25

Altogether 15.00 135.00

2. 95 μ l cDNA are diluted in preparation cDNA target storage liquid in the 2000 μ l water. The amount of cDNA is adjusted to the Ct value that provides between 10-18, usually between 12-13.

3. draw 15 μ l primer/probe mixtures and put into the suitable hole of Applied Biosystems 96 hole light reaction flat boards.

4. draw 10 μ l cDNA storage liquid put into Applied Biosystems 96 hole light reaction flat boards each hole.

5. clearly the film sealing is dull and stereotyped to use Applied Biosystems optics cap or printing opacity.

6. analyze dull and stereotyped at AB Prism 7700 sequence detectors.

Method herein also can be applicable to protein, wherein the quantitative technique of sensitivities such as enzyme linked immunosorbent assay (ELISA) (ELISA) or mass spectrum is that this area can accomplish also well-known, for detection of the amount (consulting combination WO98/24935 as a reference herein) of protein component.

Baseline spectrum data group

Provide the spectrum data group library relevant with specific group or a series of groups from single individuality with sample analysis from a large amount of group of individuals. These spectrum data groups can be used as record and are stored in the library to be used as baseline spectrum data group. Hint as term " baseline ", the baseline spectrum data group of storing as comparator in order to biology state or reagent calibration spectrum data group for information about is provided. Baseline spectrum data group can be stored in the library and in the mode of cross reference classifies. Certain classification form can be depending on the feature of the group of derived data group. Another kind of classification form may be to classify by concrete biology state. The concept of biology situation comprises the cell that can a time point in office finds or any state of cell mass. This state may reflect the geographical distribution of sample, experimenter's sex or other any identification marker. Some identification marker may be crossover. Also in described library access and single experimenter or concrete clinical testing relevant record. The classification of baseline spectrum data group can be further with relevant concrete experimenter, medical situation, concrete medical information such as reagent note in addition.

The selection of the baseline spectrum data group of carrying out for the spectrum data group of setting up calibration be use with the purpose of to be assessed, monitoring or the biology situation of estimating and calibration group (for example, monitoring drug development, quality control or other use) relevant. The baseline spectrum data group of access can be different time points, be exposed to stimulus, medicine or complex compound and from first spectrum data group from same experimenter or from different experimenters, perhaps can be from similar or dissimilar experimenter colony or tested group.

Described spectrum data group can produce from same experimenter with first data group, and sample wherein is to obtain in that separate or similar time, difference or similar site or under difference or similar biology state. For example, Fig. 5 provides before stimulation or has stimulated the rear flow process of extracting sample. Can be used as for the baseline spectrum data group available from sample after stimulating available from the spectrum data group of stimulated samples not. Baseline spectrum data group also can be from the library of the spectrum data group of the tested group of containing some special characteristic of tool or biology state or tested group. Baseline spectrum data group also can to cultivate relevant stripped or external feature corresponding with some and cell in vitro. After this spectrum data group after the calibration that produces can or separately be stored in (Fig. 6) in database or the library as record with baseline spectrum data group and first spectrum data group of choosing wantonly, although first spectrum data group is incorporated in the baseline spectrum data group usually under suitable criteria for classification. Significant uniformity is so that it is worth being stored as spectrum data between gene expression atlas and the given biology state, and it especially can be used for reaching makes the reference system aims of standardization. Standardized reference system can be used for indicating the experimenter to meet the degree of certain given biology state (healthy or ill), or for clinical intervention provides target, or play simultaneously this two kinds of effects.

Selected baseline spectrum data group also can be used as the standard of the conditions such as the efficient of judging preparation batch, toxicity. Wherein in the situation that detects the therapeutic agent effect, the base-line data group can with use this reagent before gene expression atlas corresponding. When being used for newly developing the quality control of product, the base-line data group may be corresponding with the goldstandard of this product. But, any suitable standardized technique all is applicable. For example, average baseline spectrum data group is available from the credible raw material of the herbal medicine class nutrient drug of spontaneous growth and compared different time and different batches is used the uniformity between prepared compound batch or is lack of consistency to turn out to be.

The data of calibration

We have finished the detection of gene expression under condition repeatably, i.e. the above-mentioned detection relevant with " gene magnification " with " gene expression group ", and we infer that the difference that occurs is that difference by the biology state causes under such condition. Thus we find the spectrum data group of calibrating take under the same conditions have in same experimenter's the sample height repeatability. We find that equally the spectrum data group of calibrating is repeatably in the sample that repeats to detect. We find also that wherein in the exsomatize repetition situation of the spectrum data group of obtaining calibration when being exposed to compound and the calibration characteristic that ex vivo has been exposed to the sample in the compound of experimenter's sample be comparable. Importantly, we also find, the indicating clone of processing with reagent can provide in many cases with available from the body or the spectrum data group of the comparable calibration of data group of stripped cell mass. In addition, we find to be applied to from experimenter's sample can provide on the indicator cells about the abundant calibration spectrum data group of the information content of experimenter's biology state, comprises experimenter's health status, morbid state, treatment intervention, aging degree or is exposed to the degree of environmental stimulus thing or toxin.

Calculating and the area of computer aided of the spectrum data group of calibrating

Spectrum data group available electron data table after the calibration represents or uses graphical presentations such as block diagram or form, also can the three dimensions representation represent. About the function of baseline and spectrum data can be the ratio that is expressed as logarithm. Relevant component can be listed on the x axle one by one, and the logarithm standard can be on the y axle. After the calibration member of data group can be expressed as represent for baseline that gene expression strengthens relatively on the occasion of or represent the negative value of the relative minimizing of gene expression.

Each member of spectrum data group should be repeatably within the specific limits for the similar sample of experimenter under taking from condition of similarity after the calibration. The spectrum data group of for example, calibrating can repeat in the scope of an order of magnitude for the similar sample of experimenter under taking from condition of similarity. More specifically, data can repeat in 50%, more specifically can repeat in 20%, usually can repeat in 10%. According to embodiment of the present invention, relative gene expression increase, minimizing and the unconverted pattern of each can be used for preparing the spectrum data group of calibrating in a plurality of gene locis of surveying in the gene expression group, it provide relevant biology state, certain reagent treatment condition the biology effect information be used for the experimenter or sample colony batch between relatively or be used for comparison between the cell mass. The pattern of this kind can be used for differentiating the possible candidate of drug test, can be separately or be used from diagnosis or the prognosis of relevant biology situation with other clinical indication one, perhaps can be used for instructing by preparation, detect and medicine that marketing is carried out or the exploitation of nutrient drug.

The digital material of expressing available from quantitate gene and standardized with respect to baseline spectrum data group, can be stored in database or the digital storage medium from the digital material of gene expression, perhaps be used further to comprise the health status of managing patient or carry out clinical testing or identify on the various purposes of medicine. Thereby these data can collect and converge (Fig. 8) the transmission of wired or wireless network by for example World Wide Web, Email or the Internet address or by hard copy between remote geographical position.

In embodiments of the invention, one descriptive file is stored in independent database or a plurality of database, the data of wherein storing comprises with the original gene expression data (first spectrum data group) before the conversion of baseline spectrum data group and for generation of the baseline spectrum data group record of the spectrum data group of calibrating, for example comprise about baseline spectrum data group whether from the note of specific set of landmarks and other any note of conveniently explaining and using these data.

Because data have general format, so carrying out data easily, processes by available computer. Thereby get up to provide optional corresponding to the illustrated output of calibration data group with these Organization of Datas.

For example, being at least unique samples a kind of in RNA or the protein and can using P from the experimenter_IExpression. From sample P_IFirst spectrum data group be expressed as M_j, M wherein_jTo P_IDistinct rna or the quantified measures of protein component. Record Ri is other data note in addition of the ratio of M and P and available relevant experimenter's situation, for example, age, diet situation, race, sex, geographical position, SOM, psychataxia, medicine are processed, activity, body weight and the environmental exposure factor etc. of health. In addition, data are processed and are comprised that further access is from data in the second situation database of other medical data that do not have in the spectrum data group that may contain current calibration. At this therebetween, data access can be undertaken by computer network.

Above-mentioned data storage on computers can provide the user can obtain the information of form. Therefore, the user can store these information into second position, comprises the described information of downloading. But, thus access can be confined to know that the user that password or other arrange safely can protect wherein contained medical records. The feature of this embodiment of the present invention is the user can add new or thereby note is crossed is recorded to and makes a part that is recorded as biology information in the data group.

With such as the diagram of the spectrum data group of the relevant calibration of the products such as the medicine mode by the calibration collection of illustrative plates, more specifically be that the mode by the sign collection of illustrative plates provides a chance for the standardization of product. Described collection of illustrative plates can be used as the feature of the relative potency when comparing because of other medicines similar or that different application is got permission, difference of mechanism of action etc.

Various embodiments of the present invention also can be used as the use that computer program is used for computer system. Described product can comprise for deriving first spectrum data group and for generation of the program code of the collection of illustrative plates of calibration. Such operation may comprise a series of computer instructions that are fixed on the practical medium, such as computer-readable medium (for example, disk, CD-ROM, ROM or hard disk), perhaps can be sent to a series of computer instructions of computer system by adjusting demodulator or other interface device, such as communications adapter connected to the network. Described network connection can be by optical cable for example or wire communication cable or certain combination by wireless technology (for example, microwave, infrared ray or other tranmission techniques) or these modes. This family computer instruction preferably comprises the function of aforesaid relevant this system of all or part this paper. Those skilled in the art will be appreciated that described computer instruction can be write down for many Computer Architectures or operating system with many program languages and uses. In addition, such instruction can be stored in any memory storage, such as semiconductor, magnetic, optics or other memory storage in, and available any communication technology propagates, such as optics, infrared ray, microwave or other tranmission techniques. Estimate that such computer program can (for example distribute by subsidiary removable medium printed or electronic document page, the pre-packing software that shortens), preloaded computer system (for example, system ROM or fixed disk), perhaps divide the electronic bulletin board from server or network (for example, internet or World Wide Web). In addition, computer system can be first data group of derivation and further provides the group etc. of deriving that comprises with calibration spectrum data group.

Described in WO01/25473, the index that the calibration spectrum data group of figure or form, relevant database and calculating are good or the algorithm of derivation are can be various purposes or separately sale with the information of extracting from group, database, data group or index or algorithm.

Index Establishment

Generally speaking, (i) but cross over tested group or tested group or sample or cross over cell mass relevant biology situation gene expression atlas remarkable uniformity and (ii) basically use the method that component duplicate measurements value in the gene expression group that produces gene expression atlas is provided under the similar measuring condition in the specificity of group all components and amplification efficient so that might use certain index identified gene expression map and so detection of biological situation.

With the numerical value in the gene expression atlas can be set up index with the target function of the single numerical value mapping that the biology state is relevant at hand. Numerical value in the gene expression atlas is the amount with each component of the corresponding gene expression group of gene expression atlas. These group components have consisted of the spectrum data group, and target function has produced single numerical value from the spectrum data group membership-certain index.

Target function can be built into every linear summation easily, and every is our so-called spectrum data group membership " Contribution Function ". For example, described Contribution Function can be spectrum data group membership's constant power. Therefore target function has following form:

$I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)},$

Wherein I is index, M_iThe numerical value of spectrum data group membership i, C_iBe constant, and P (i) is M_iThe power that improves, summation are the integer value formation for all i, and i can reach the number of members in the data group. We have obtained the polynomial expression of a linearity thus.

Numerical value C_iAnd P (i) can measure in many ways, thereby makes index I provide associated biomolecule to learn the information of situation. A kind of mode is that applied statistics learns a skill, and such as latent class model, makes spectrum data group and clinical data or experiment come source data or other data relevant with the biology situation to connect. In this contact, for example, can use the Innovations from Statistical, Belmont, Massachusetts are called as Latent Gold^Software. Consult at this combination webpage as a referencewww.statisticalinnovations.com/lg/。

Perhaps, can use in a manner known in the art other simpler modeling technique. For example, the mode that the value that inflammation (according to what measure for the spectrum data group of inflammation gene expression expression map) that can heavier degree and target function are larger is associated makes up the target function of inflammation. Therefore, in a simple embodiment, each P (i) may be+1 or-1, this depends on that the component that increases the weight of along with inflammation is to increase or reduce. As hereinafter further discuss, we have made up a significant inflammation index that matches with expression

1/4{IL1A}+1/4{IL1B}+1/4{TNF}+1/4{INFG}-1/{IL10}，

Wherein the braces around the component points out it is the measured value of these components, and these components are subsets of table 1 inflammation gene expression expression group.

The standardization that can be as mentioned above be used for as baseline spectrum data group providing suitable with reference to and even can be used for setting up the spectrum data group of calibrating, as mentioned above, based on standardized reference, the index that characterizes gene expression atlas also can have the standardized value of this target function to be used for setting up this index. This standardized value can be measured with relevant tested group or tested group or sample or relevant cell mass, thereby can think that this index is relevant with standardized value. Relevant experimenter group or experimenter's group or sample or relevant cell mass can have at least one denominator in the following characteristics: the range of age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine processing, body movement, body weight and environmental exposure factor.

For example, described index can be configured to, about the standardized gene expression atlas for the tested group of health or tested group, so that reading is approximately the 1 standardization gene expression atlas that characterizes the health volunteer. We can further suppose, described index for the biology state be inflammation, the reading 1 among this embodiment is therefore corresponding to the gene expression atlas that meets health volunteer's standard. Those obvious higher readings may be differentiated the experimenter who is in the inflammation state. But, the standardized value that uses 1 conduct to determine is a possible selection, and another is reasonably selected is the standardized value that uses 0 conduct to determine. When doing this selection, index can standard deviation units represent 0 depart from, thus make-1 and+numerical value between 1 comprises the tested group of reference of 90% normal distribution or tested group. Therefore we have found that gene expression atlas numerical value (and the index that makes up based on their) trends towards normal distribution, and the index centered by 0 that makes up in this way is the information that highly is rich in. Therefore made things convenient for the use of index in medical diagnosis on disease and therapeutic purpose are set up. Select 0 as standardized value and use standard deviation units for example can consult following Figure 17 B.

                         Embodiment

Embodiment 1: the acute inflammation index that helps to analyze large amount of complex data group.In one embodiment of the invention, desired value or algorithm can be used for the complex data group is reduced into the single desired value that experimenter's inflammation state relevant information is provided. Described in Figure 1A and 1B.

Figure 1A is entitled as in a huge complex data group certain experimenter accurate inflammation collection of illustrative plates tracking results of originating. The figure illustrates during single male sex experimenter suffers from optic neuritis 8 and detect result from 24 genes (as shown in table 1) of inflammation gene expression expression group the different dates.

Figure 1B has shown the application of acute inflammation index. The data of showing among above Figure 1A are shown among this figure after the target function calculating of using corresponding to following mathematic(al) representation: (1/4{IL1A}+ 1/4{IL1B}+1/4{TNF}+1/4{INFG}-1/{IL10}).

Embodiment 2: acute inflammation index or algorithm are in monitoring sample or the experimenter's biology situation Use.Experimenter's inflammation state has disclosed past process, future development, the information such as reaction to treating of relevant biology situation. The acute inflammation index can be used for disclosing these information of relevant experimenter's biology situation. As shown in Figure 2.

Detect the single block diagram after result's (showing 24 genes of every delegation among Figure 1A) that inflammation gene expression expresses is shown as calculating every day. Index has disclosed and may intervene in the relevant inflammation state clearly trend (Fig. 2) with treatment.

Fig. 2 is in the diagram from the acute inflammation index of calculating in by 9 of the single patient blood of therapeutic treatment different significant clinical critical events because of optic neuritis. The change of the desired value of acute inflammation index is strongly relevant with the Expected Results that treatment is intervened. Four clinical critical events have been marked the top of acute inflammation index in this figure, comprise that (1) is before with the steroids treatment, (2) process with 1 gram IV Solu-Medrol every day, (3) every day, then oral 60mg metacortandracin tapered to after the treatment of 10mg every day and after (4) treatment. The data group is identical with Fig. 1's. Index and 1/4{IL1A}+ 1/4{IL1B}+1/4{TNF}+1/4{INFG}-1/{IL10} are proportional. Just as expected, the acute inflammation index reduces rapidly after with the treatment of IV steroids, raise to some extent during oral metacortandracin carries out the lower processing of curative effect, and steroids no longer continue to add and fully metabolism got back to the front level for the treatment of after falling.

Embodiment 3: utilize acute inflammation target setting dosage,Comprise concentration and time, for the compound in the exploitation or for compound to be tested in people and inhuman experimenter as shown in Figure 3. The acute inflammation index can be used as without the treatment of the acting in conjunction mechanism common reference point with compound or Intervention Therapy. Brought out by described index and shown the Gene response of this compound but the compound that do not improve known biology situation can compare from the different compounds that have different effectiveness in this biology situation for the treatment of.

Fig. 3 has shown the effect of using single dose 800mg ibuprofen in the single donor of identifying according to the acute inflammation index. Single experimenter is at the time point picked-up 800mg of 0 time point and 48 hours OTC brufen. The gene expression value of in 2,4,6,48,50,56 and 96 hours, measuring 5 inflammation related gene sites of appointment as described below. Just as expected, the inflammation index descended immediately behind picked-up non-steroidal anti-inflammatory brufen and got back to baseline after 48 hour. Took at 48 hours second dose abide by with first dose of same dynamic law and at the experiment terminal point and located to get back to baseline in 96 hours.

Embodiment 4: utilize the acute inflammation index to identify the effect of certain reagent, security and physiology work Use pattern,It may be in developing and/or may be complicated at occurring in nature. Described in Fig. 4.

Fig. 4 shows that the acute inflammation index of illustrated calculating is for five kinds of different situations, comprise (A) untreated whole blood, (B) whole blood of processing at a kind of non-active carrier Compound D of external use MSO, (C) external use dexamethasone (0.08ug/ml) process without other whole blood that stimulated, (D) whole blood that stimulates at a kind of known short scorching compound lipopolysaccharides (LPS, 1ng/ml) of external use and the whole blood of (E) processing at external use LPS (1ng/ml) and dexamethasone (0.08ug/ml). Dexamethasone is the prescription medicine that usually medically is used as the anti-inflammatory steroid compound. Calculate the acute inflammation index from the gene expression dose of the inflammation related gene of the people's whole blood available from single patient, expressing of measuring. For gene IL1A, IL1B, TNF, IFNG and IL10, the result of mrna expression is expressed as Ct's in this embodiment, but also can be expressed as, for example, relative fluorescence unit, copy number or other any can be quantitative, accurately with the form of calibrating. Determine proportional acute inflammation value according to algebraic expression 1/4{IL1A}+1/4{IL1B}+1/4{TNF}+1/4{INFG}-1/{IL10} by the gene expression value.

Embodiment 5: derive and application for colony's standardized value of gene expression atlas.Fig. 6 and 7 has shown available from two unique patient groups (patient's group) whole blood and for the arithmetic mean of instantaneous value of gene expression atlas (having adopted 48 sites of the inflammation gene expression expression group of table 1). These patient's groups all are normal or not yet diagnosed. Be confirmed as first patient's group of Bonfils (drawing point is represented by rhombus) by 17 experimenters' compositions as the blood donor of Bonfils Blood Center (Denver, crolla is many). Second patient's group has 9 blood donors, and its gene expression atlas is available from the assay of having carried out 4 times in all around. Experimenter's (drawing point is represented by square) in this second patient group be assignee by this paper from Source Precision Medicine, recruit among the employee of Inc.. Calculate the average expression of each colony in 48 gene locis of gene expression inflammation group each. The result of site 1-24 (hereinafter being sometimes referred to as inflammation 48A site) as shown in Figure 6, and the result of site 25-48 (hereinafter being sometimes referred to as inflammation 48B site) is as shown in Figure 7.

The uniformity of gene expression dose was significant between two different patients organized. The gene expression dose that two patients group all demonstrates in 48 sites each between two groups without significant difference. This observed result shows that people's inflammation gene expression has the expression pattern of " normally ", the gene expression atlas that utilizes the inflammation gene expression expression group (or its subset) of table 1 and do has characterized described expression pattern, and colony-normal expression pattern can be used for, for example, instruct the medical science intervention that any biology situation that causes the normal expression pattern to change is carried out.

Fig. 8 has shown in similar blood vessel equally the arithmetic mean of instantaneous value for gene expression atlas (reusing 48 sites of inflammation gene expression expression group in the table 1) available from two different patient groups (patient's group) whole blood. Its expression value is 24 normally patients diagnoseds' (therefore not suffering from known inflammatory diseases) not by patient's group of triangle data point representative. Its expression value is the failed patient of 4 trouble rheumatoid arthritis and treatment (therefore suffering from unsettled rheumatoid arthritis) by another patient's group of rhombus data point representative.

Significant as the uniformity of data between the different normal patient's group of two shown in Fig. 6 and 7 is the systemic difference of data between the normal and ill patient's group shown in Fig. 8. Shown among 45 of 48 inflammation gene expression sites, unstable rheumatoid arthritis patient's inflammation gene expression is expressed average level, and (lower circulation threshold value Ct) is higher than not ill experimenter. Therefrom the data group that further confirmed to utilize gene expression to confirm to have specific biology situation whether carefully designed and controlled precision and the scale that need detect according to the requirement of this paper.

Fig. 9 is to have shown equally the gene expression atlas arithmetic mean of instantaneous value of organizing 24 sites in the table 1 inflammation gene expression expression group of whole blood available from two different patients from the similar form of Fig. 8. Its expression value with patient's group of rhombus data point representative be 17 as the blood donor normally, do not make a definite diagnosis experimenter's (therefore not suffering from known inflammatory disease). Its expression value is same normal and not yet diagnosed 16 patients with another patient's group of square shape data point representative, they monitored 6 months, and the average of these expression values is with the representative of box-shaped data point. Therefrom the gene expression value average of first health population of transverse axis conform to very much with second health population gene expression value average of the longitudinal axis, the expression value that detects difference on the corresponding basis of gene-gene be approximately 7% or still less.

Figure 10 has shown the gene expression numerical value (having utilized 14 sites of table 1 inflammation gene expression expression group) (data that shown 10 experimenters) of normally not making a definite diagnosis blood donor's whole blood available from 44. In addition, each member's gene expression value conforms to whole group value very much in colony's (group), and the peak height that shows as each gene loci on the figure is consistent. The result that other experimenter of this group and other gene loci outside the site shown here present is with shown here consistent.

The inference of carrying out according to these principles and in many embodiments of the present invention, the colony's standardized value that is used for gene expression atlas can be used for the biology situation of comparative assessment individual subjects, comprises healthy and/or ill. In one embodiment, standardized value for gene expression atlas can be used as baseline calculating for experimenter " calibration spectrum data group " (beginning defined according to this part), to disclose the deviation between described experimenter's gene expression and the colony's standard value. Colony's standardized value for gene expression atlas also can be used as baseline value when structure meets the target function of embodiment of the present invention. Therefore, for example, the target function of structure usually can not only disclose individual inflammation and express degree, but also relevant with standardized value.

Embodiment 6: the time-independent uniformity of gene expression group component expression value can be used as life Thing is learned the reliable indication of situation.Figure 11 has shown single experimenter each expression in 84 genes that detect per month the middle of the month (in the table 1 in the inflammation gene expression expression group). As seen expression significantly was consistent within whole period.

Figure 12 is similar with 13 has shown respectively among the different single experimenters (selecting based on feeling good and not taking medicine in each case) each expression of 48 genes (in the table 1 inflammation gene expression expression group), detecting weekly in around in Figure 12 being, is to detect per month in 6 months in Figure 13. In each situation, expression all significantly is consistent within whole period equally and is similar between individuality.

Figure 14 has also shown when the inflammation gene expression expression group with table 1 detects the impact on inflammatory gene expression among the single people experimenter of using of within a period of time anti-inflammatory steroid. 24 sites in 48 sites have been showed in this case. From the experimenter, extract the benchmark blood sample to PAX RNA separator tube, then the experimenter is used 60mg single dose metacortandracin, a kind of anti-inflammatory prescription steroids. Extracted other blood sample in oral rear 2 hours and 24 hours at this independent medicine once. The gene expression results of showing all three time points, wherein the numeric representation of authentic specimen is the unit of x axle. As desired, rear 2 hours block diagram is shown according to using, and oral metacortandracin has caused most of inflammation related gene site to express decline. But, use rear 24 hours block diagram and show that most gene site gene expression dose in the time of 24 hours that gene expression reduces in the time of 2 hours increases.

Although the baseline among Figure 14 be before the dispenser relevant with single tested individuality the gene expression value as the basis, but as can be known, healthy individual trends towards utilizing the colony's standardized value in the gene expression atlas that table 1 inflammation gene expression expression group (or its subset) does from previous embodiment for we. We infer in the trial that the inflammatory gene expression dose is returned to shown level in Fig. 6 and 7 (normal or set level) from Figure 14; disturbing normal expression to cause the compensatory gene expression reaction of overcompensation for the medicine induced reaction, may be because metacortandracin significantly has been metabolized to the form of non-activity or has cleared out from the experimenter.

Figure 15 with the similar mode of Figure 14, shown by the whole blood sample available from people experimenter and within a period of time, to have used the impact that the single dose metacortandracin is expressed 5 kinds of genes (from the inflammation gene expression expression group of table 1). When using metacortandracin (t=0) and use after 2 hours and 24 hours the sampling. The gene expression atlas of this sample after every part of whole blood sample stimulates by interpolation 0.1ng/ml lipopolysaccharides (Gram-negative endotoxin) stimulation and mensuration. As seen when using for the gene expression dose of (t=0), 2 hours sample demonstrates in the inflammation gene expression expression group 5 locus genes and expresses significantly and reduce. Used rear 24 hours, the inhibitory action of metacortandracin is no longer obvious, the level when in fact 3 gene expression doses in 5 sites are higher than t=0, and this has quantitatively illustrated well-known bounce-back effect on molecular level.

Figure 16 has shown that also using within a certain period of time TNF-suppresses compound to the impact of inflammatory gene expression in the single rheumatoid arthritis patient, the mean value in similar site compares to illustrate but expression described herein and previous mensuration (with Fig. 6 and 7 relevant) normal (that is, do not make a definite diagnosis, healthy) patient organizes. As the part of the relatively large international research that relates to rheumatoid arthritis, tracked 12 weeks of monitoring of experimenter. It is because the Planning Change therapy is also treated with TNF-inhibition compound immediately to the conservative medicinal treatment of rheumatoid arthritis is reactionless that the experimenter enters this research. Before beginning, new therapy gets blood (access 1). After the new therapy of beginning, 8 weeks (access 3) and 12 weeks (access 4) were got blood after 4 weeks after therapy changes (access 2), new therapy began. Collect blood in PAX RNA separator tube, room temperature was placed 2 hours and is frozen in-30 ℃.

With the central laboratory of frozen sample shipping to Source Precision Medicine, supply at Boulder, this paper assignee of Colorado measures the expression of 48 genes in the table 1 inflammation gene expression expression group. Blood sample and extract RNA by the step of manufacturer recommendation thaws. RNA is transformed into cDNA and measures the expression of 48 inflammatory genes. Figure 16 has shown in 48 genes 11 expression of results. In the time will comparing with colony's mean value of the normal blood donor of the U.S. from the expression of results in access 11 sites of 1, the experimenter demonstrates sizable difference. Same, with after in several times doctor's access each time each locus gene expression of gained compare with same normal mean value. From access 2,3 and 4 digital proof change the effect of therapy. In the each time access after therapy changes, there is the inflammatory gene expression dose in 10 sites to approach previous normal (that is, do not make a definite diagnosis, the healthy) patient who measures in 11 sites and organizes the mean value in similar site.

Figure 17 A further illustrated one group 44 normally, do not make a definite diagnosis among the blood donor (the inflammation gene expression expression group of table 1) the inflammatory gene expression uniformity described herein in relevant 7 sites. The numerical value of demonstration is in average expression value ± 2 standard deviation scopes for each independent site, and this is equivalent to 95% normally distributed population. Although the amplitude of confidential interval large (95%), attractive be detected gene expression value (Δ CT) still drop on mean value 10% in, regardless of relevant expression. As what hereinafter be described in further detail, for given biology situation, can set index to detect described symptom. This may be the result of two kinds of situations associating: (i) having the gene expression atlas uniformity and (ii) have the method that produces the gene expression group component measured value that basically repeatably can derive gene expression atlas, described detection between biology situation and colony is that the specificity of group all components and amplification efficient are basically carried out under the similar measuring condition and so obtained the measured value of biology situation. Therefore, the function of representative component site expression value is used herein among Figure 17 A derives the inflammation desired value, and it is by standardization, thereby makes reading 1 corresponding to health volunteer's component expression value, shown in the part of the right hand among Figure 17 A.

In Figure 17 B, measured the inflammation desired value of not making a definite diagnosis each member among the blood donor for one group 42, and the desired value shown in the figure distributes and as seen approximately to be similar to normal distribution, although the big or small less of experimenter's group. Desired value shows as with respect to take 0 intermediate value as the basis, with the standard deviation units calibration deviation from intermediate value. Therefore 90% experimenter group drops in 0 value+1 and-1 scope. We have also set up the various indexs of showing analogue.

The application of the index that Figure 17 C is identical with Figure 17 B, wherein the inflammation intermediate value with the normal experimenter of colony is made as 0, and normal subjects and ill experimenter are all with the standard deviation units mapping with respect to this intermediate value. Measure normally, do not make a definite diagnosis the inflammation desired value (black post) of each member in 70 individualities of colony. As seen the desired value of the generation shown in Figure 17 C distributes roughly near normal distribution. Same, calculate desired value from two ill batch totals, (1) with methotrexate (MTX) (MTX) treatment and will be with the rheumatoid arthritis patient of more effective medicine (such as tnf inhibitor) treatment, (2) the rheumatoid arthritis patient who uses the antirheumatic disease medicine (DMARDS) that improves symptom except MTX to treat, they also will change into more effective medicine treat (as, MTX). Two groups of patients all present and compare the desired value (showing that inflammation increases the weight of) that is tilted to normal distribution. Therefore this Figure illustrates to utilize and derive from the index evaluation disease condition of gene expression atlas data and objective and a therapeutic purpose that can be quantitative is provided. After these two groups of experimenters were carried out appropriate treatment, two groups desired value all was returned to more normal distribution (data are not shown in this).

Figure 18 is to have drawn two groups of different 6 experimenters' rheumatoid arthritis patient for the gene expression atlas in 7 identical among Figure 17 A sites from Figure 17 A similar mode. A colony (being marked by in the drawings " stable ") is the patient good to therapeutic response, and another group's (being marked with in the drawings " unsettled ") is bad to therapeutic response and the patient of the positive Planning Change of its therapy. As seen the expression value of stablizing patient group drops in the scope of 95% confidential interval, and for unstable patient group, have 5 expression value to drop on outside this scope in 7 sites and on. The right hand partial display of this figure is compared with normal not patient diagnosed group's numerical value 1, and unstable group average inflammation index is 9.3, and the average inflammation index of stablizing colony is 1.8. This index provides the examination criteria of a potential inflammation order of severity thus, and described inflammation is rheumatoid arthritis in this case. Therefore this index also can be used for detecting the effectiveness for the treatment of and provides target for treating to intervene except the measured value as the biology situation.

Figure 19 therefore for example understand the inflammation index in assessment to the application among the single rheumatoid arthritis patient of traditional methotrexate (MTX) therapy poor response. This experimenter's inflammation index appears at ultra-Right side when (tnf inhibitor) in the new therapy of beginning, afterwards 2 weeks, 6 weeks and 12 weeks continued to move to left. As seen this index is tending towards normal value, and is consistent to the response situation of new therapy with the patient that the doctor observes.

Figure 20 has described when new therapy (also using tnf inhibitor) beginning and 2 weeks and 6 weeks used the inflammation index evaluations to 3 rheumatoid arthritis patients of traditional methotrexate (MTX) therapy poor response afterwards equally. Index in the visible various situation is tending towards normally usually again, and is consistent to the response situation of new therapy with this patient that the doctor observes.

Figure 21-23 has shown respectively an international category rheumatic arthritis patient inflammation index, and wherein everyone is treated the doctor and is accredited as stable (that is, inexpectancy need change therapy). Figure 21 has shown each the index with 10 patients in the group of methotrexate for treatment, but known methotrexate (MTX) mitigation symptoms but do not touch the root of disease. Figure 22 has shown that with 10 patients index separately in Enbrel (a kind of tnf inhibitor) treatment group, Figure 23 has shown with 10 patients index separately in Remicade (another kind of tnf inhibitor) treatment group. As seen each patient's inflammation index increases with the normal phase ratio among Figure 21, and in Figure 22, has with normal value as a class with the patient of Enbrel treatment to connect much closer inflammation index (80% in normal range (NR)). In Figure 23, although the patient's of the visible useful Remicade treatment of institute except a patient inflammation index all is in normal or is lower than normally, wherein two patients have unusually low inflammation index, shown the immunosupress of this medicine is replied. (in fact, studies show that Remicade is relevant with serious infection in some experimenter, immunosuppressive action herein is by quantitative. ) equally in Figure 23, an experimenter has the inflammation index in the normal range (NR) of being significantly higher than. In fact, the anti-inflammatory steroids (metacortandracin) that this experimenter takes reduces gradually, and in the about week, experimenter once clinical symptoms significantly strengthens behind the inflammation index determining.

Strikingly, these embodiment have shown that the blood testing by chemically examining from the experimenter obtains the measured value relevant with experimenter's rheumatism. If it is relevant with the inflammation degree to be somebody's turn to do detection, can expect that other take the symptom of inflammation as the basis, comprises that for example, angiocardiopathy can be monitored in a similar manner.

Figure 24 has described and has utilized the inflammation index evaluation with the single inflammatory bowel disease patient of three doses of Remicade initial treatments. The figure illustrates and face first dose of inflammation index before using, and first dose used rear 24 hours, this index is returned in the normal range (NR). This index just improved before using second dose, but was in the normal range (NR) before using the 3rd dose. In addition, except the measurement standard that the biology situation is provided, this index is used herein to the effectiveness that detects therapeutic agent (Remicade), and provides target for the treatment intervention of dosage and two kinds of forms of progress.

Figure 25 shown with other NSAIDs (NSAIDs) and compared, the gene expression atlas of in the whole blood that the external use brufen is processed 24 sites (inflammation gene expression expression group in the table 1). For the collection of illustrative plates of brufen in front. As seen all NSAID that comprise brufen have a basically similar collection of illustrative plates, and wherein the gene expression pattern between the site is similar. Although have these similarities, each medicine has the characteristic of self uniqueness.

That Figure 26 has described is how objective, quantitative, accurately and the repeatably relatively effect of two kinds of competitive anti-inflammatory agents. In this embodiment, detected in one group of two gene (table 1 is in inflammation gene expression expression group) expression of each for the various dose (0.08-250 μ g/ml) of each medicine in external whole blood. The leading medicine of this listing demonstrates has complicated relation between dosage and inflammatory gene response. Self-contradictory is that in the case of the leading medicine that goes on the market, when dosage increased, the gene expression in two sites began all to descend and then raises again. For other compound, reaction result is more consistent, thereby when dosage increases, all more consistent decline of the gene expression in two sites.

Figure 27 to 41 has described the application of gene expression group in the early stage evaluation of infectious disease and monitoring. The expression product that these figure have drawn the gene that indicates in whole blood to using the reaction of different infectious agents or infectious agent Related product. In each figure, according to term defined herein, compare " calibration " gene expression dose with using the baseline expression that applies relevant infectious agent WBA before. In this, a plurality of figure of the patent application WO01/25473 that hereinafter mentions with us in itself of described figure (for example, wherein Figure 15) are similar. The form that the concentration of accordingly time point monitoring changes to measure in proportion after adding infectious agent or other stimulus shows that the baseline values 1 for concrete gene loci is corresponding to the described site expression identical with expression before the interpolation stimulus. Concentration changes scale on logarithmic coordinates. Rod below unified line represents concentration and descends, and the rod more than unified line represents concentration to be increased, and each excellent order of magnitude represents to change the order of magnitude of ratio. We prove in WO01/25473 and other experiment, under suitable condition, can represent the gene expression atlas that is exposed in vivo in the corresponding stimulus external by whole blood being exposed to the gene expression atlas that obtains in the stimulus.

Figure 27 has utilized one for distinguishing the new bacteria gene expression group of 24 genes that various bacterium situations are researched and developed in the host living beings system. Two different stimulus have been used: fat teichoic acid (LTA), a kind of gram-positive cell wall fraction; And lipopolysaccharides (LPS), a kind of gram-negative cells wall fraction. The final concentration of namely surveying after stimulus is used is 100ng/mL, 2 hours and the expression variation ratio of monitoring in 6 hours for level before using after each stimulus is used. As seen early just can observe different expression in 2 hours after use, for example, in the IFNA2 site and other can distinguish that other other site of Low Response is located between Gram-positive and the gramnegative bacterium.

Figure 28 has shown that IFNG place, single site is for the different expression of three kinds of separate sources (streptococcus pyogenes, bacillus subtilis and golden streptococcus) LTA. Each stimulus application concentration is 100 ng/mL, monitoring reaction situation after 1,2,4,6 and 24 hour after using. The result shows that gene expression atlas can be used for the infectious agent of distinguishing different, is different types of gram-positive bacteria at this.

Figure 29 and 30 has shown that respectively the inflammation 48A in the whole blood (specifying concentration, is respectively 10 after just having used with 48B locus (relevant with above-mentioned Fig. 6 and 7 respectively) to using golden streptococcus stimulus and Escherichia coli stimulus⁷With 10⁶CFU/mL) reaction, with use before the baseline monitoring of comparing after using 2 hours. These figure demonstrate in rear two hours of infection has many reactions that have to coli-infection in the described site.

Figure 31 with 32 respectively corresponding to Figure 29 and 30 and similar to them, so the monitoring that difference was carrying out after using in 6 hours. More site is for the reaction that has of infecting. Demonstrate diacritic expression between two kinds of infectious agents such as a plurality of sites such as IL2.

Figure 33 has shown that (concentration after just having used also is 10 for applying the Escherichia coli stimulus in inflammation 48A site⁶CFU/mL) and apply and contain the Escherichia coli product but without the reaction of the Escherichia coli filtered fluid of coli somatic. Reaction is monitoring in 2,6 and 24 hours after applying. As seen, for example, site IL1B, IL18 and CSF3T are different to the reaction of Escherichia coli and ECF in time.

Figure 34 is similar to Figure 33, but is to from the stimulus of independent ECF with the stimulus reaction of the ECF that adds a kind of antibiotic-PB in conjunction with lipopolysaccharides (LPS) of controlling oneself in the reaction that this compared. For example, the reaction detection of IL1B shows that the existence of PB does not affect this site to the reaction of ECF, thereby shows that LPS causes IL1B to a factor of ECF reaction.

Figure 35 has described in the whole blood inflammation 48A site and has changed in time that (concentration after just having applied is 10 to golden streptococcus stimulus⁷CFU/mL) reaction, monitoring in 2,6 and 24 hours after applying. As seen time dependent reaction can comprise the trend of expression and the order of magnitude that wherein changes. (consult, for example, IL5 and IL18. )

Figure 36 and 37 has shown respectively that in 6 hours the inflammation 48A of monitoring and 48B site are to (concentration after just having applied is 10 from Escherichia coli⁶With 10²CFU/mL) stimulation and from golden streptococcus (concentration after just having applied is 10⁷With 10²The reaction of stimulation CFU/mL). As seen, in other cases, in a plurality of sites, such as B7 (Figure 36), TACI, PLA2G7 and C1QA (Figure 37), the reaction that Escherichia coli produce is much more remarkable than golden streptococcus generation. The proof that these data are strong gene expression atlas can be used for the existence of highly sensitive evaluation Gram-negative bacteria and come with gram-positive bacteria difference.

Figure 38 and 39 has shown that respectively (the separately concentration after just having applied is 10 to the golden streptococcus of high concentration and Escherichia coli separately for the inflammation 48B that monitored in 2,6 and 24 hours and 48A site after using⁷With 10⁶CFU/mL) reaction that stimulates. Pass in time reaction at place, many sites and be included in variation on quantity and the direction. Figure 40 is similar to Figure 39, but demonstration is the reaction in inflammation 48B site.

Figure 41 has shown that equally (the separately concentration after just having applied is 10 to the golden streptococcus of high concentration and Escherichia coli respectively for 24 hours monitor after using inflammation 48A site⁷With 10⁶CFU/mL) reaction that stimulates. The same with the situation of Figure 20 and 21, the reaction in some sites such as GRO1 and GRO2 is had any different between two types of infection.

Figure 42 has described the effective member who statistics T-check is applied to differentiate the characterizing gene expression group that can distinguish between normal subjects and the unstable rheumatoid arthritis patient. The box that becomes ash is illustrated in distinguishes between two groups of experimenters the individually very effectively gene of (the P value of t check marks in the box on each figure right side), thereby has pointed out the effective member for the characterizing gene expression group of rheumatoid arthritis.

Figure 43 has described the expression of one group of 17 gene for 8 doubtful bacteremia patients. These data have reference value for the bacteremia patient who seeks the gene expression of tool feature mode.

Figure 44 has described the effective member who statistics Y-check is applied to differentiate the characterizing gene expression group that can distinguish between normal subjects and the bacteremia patient. The box that becomes ash is illustrated in distinguishes between two groups of experimenters the individually very effectively gene of (the P value of t check marks in the box on each figure right side), thereby has pointed out the effective member for the characterizing gene expression group of bacteremia.

Figure 45 has described the application of an algorithm (as shown in FIG.), has obtained the index of correlation of the rheumatoid arthritis (RA) when being applied to respectively normal subjects, rheumatoid arthritis patient and bacteremia patient. This index can be distinguished out from normal subjects and bacteremia patient with RA patient easily.

Figure 46 has described the application of an algorithm (as shown in FIG.), has obtained the bacteremia index of correlation when being applied to respectively normal subjects, rheumatoid arthritis patient and bacteremia patient. This index can be distinguished out from normal subjects and rheumatoid arthritis patient with the bacteremia patient easily.

These data have been supported our conclusion, that is, precision as described herein and the enough gene expression atlas (1) of calibration can detect has the individual subset that known organism is learned situation; (2) can be used for monitoring the patient to the reaction for the treatment of; (3) can be used for assessing effect and the security for the treatment of; And (4) can make one or more relevant gene expression atlas more instruct treatment for the patient near one group of desired value by adjusting therapy, and described desired value may be standardized numerical value or other expection or accessible numerical value. Even we have proved blood or other tissue of processing from exsomatizing, gene expression atlas also can provide significant information. We have proved that also the gene expression atlas from the periphery whole blood provides the symptom information of wide region, no matter are direct or usually relevant with blood.

In addition, in embodiments of the invention, gene expression atlas also can be used in the sign of the infectious disease such as septicemia and early stage evaluation the (comprise symptom before state). Described sign comprises stage (such as early stage or late period) and the prognosis of natural history of pathogen, the infection of individuality, bacterium and the virus infections of the infected and uninfection of difference, specific hypotype. Utilizing above-mentioned algorithm and statistical method to finish described evaluation is also distinguished in the scope that also is in this paper multiple embodiments in this way.

Table 1. Infectious Diseases or the infectious disease inflammation gene expression expression group (Gene Expression Panel) of being correlated with
				Symbol	Title	Classification	Describe
ABCC1	ATP is in conjunction with box, the C subtribe, and the member 1	Protein called membrane transporters	AKA MRP1, ABC29: how special organ anionic membrane transport protein, protective tissue is resisted various xenobiotics because they can be removed from cell when crossing expression.
				ABL1	V-ab1 Abelson mouse leukemia oncogene homologue 1	Oncogene	In Cell Differentiation, division, adhere to and coerce the cytoplasm and the nucleoprotein EGFR-TK that relate in replying. The variation of ABL1 has caused vicious transformation.
ACPP	Acid phosphatase, prostate	Phosphatase	AKA PAP: prostatic main phosphatase, synthetic under the androgen regulation and control, secreted by prostate epithelial cell.
				ACTB	The β actin	Eucaryotic cell structure	Actin is the protein of the high conservative that relates in cell mobility, structure and the integrality. ACTB is one of two kinds of non-muscularity cell skeletal actins. Effect site for cytochalasin B is influential to cell mobility.
ADAMT   S1	Desintegration element sample and metalloproteinases (reprolysin type) with 1 type thrombospondin motif	Protease	AKA METH1 suppresses endothelial cell propagation, may suppress Angiogenesis, and its expression may be relevant with the development of cancer cachexia.
				AHR	Aromatic hydrocarbon receptor	Metabolism acceptor/transcription factor	Responsive plane aromatic hydrocarbons in conjunction with improving (that is, P450) the expression of xenobiotics metabolic enzyme.
ALB	Albumin	The healthy indication of liver	The carrier protein that finds in serum synthesizes in liver, and its downward modulation is weak relevant with liver function/health status.
				APAF1	Apoptosis protease-activating factor 1	Protease activated peptide	Cromoci is combined with APAF1, has started the activation of CASP3, causes Apoptosis. May also promote the procaspase9 self-activation.

Symbol	Title	Classification	Describe
				ARG2	Arginase II	Enzyme/redox	The catalysis arginine is hydrolyzed into ornithine and urea, may work in the synthetic downward modulation of nitric oxide.
B7	B7 albumen	The conduction of cell signal and activation	May the modulin relevant with lupus
				BAD	The BCL2 activator of cell death	Memebrane protein	Form heterodimer and resist its dead repressor active with BCLX. This has replaced BAX and has recovered the activity of its inducing cell apoptosis.

Symbol	Title	Classification	Describe
				BAK1	BCL2-antagonist/inhibitor (killer) 1	Memebrane protein	When having suitable stimulation, BAK1 by in conjunction with and antagonism repressor BCL2 or its adenovirus homologue elb 19k albumen accelerated programmed cell death.
BAX	The BCL2 X albumen of being correlated with	Inducing apoptosis-germ cell development	Accelerate programmed cell death by combination and antagonism apoptosis repressor BCL2, may bring out the caspase activation
				BCL2	B-cell CLL/ lymthoma 2	Inhibitors of apoptosis-cell cycle regulation and control-neoplasia	By hindering the activation blocking-up apoptosis of caspases
BCL2L1	BCL2-sample 1 (microscler)	Memebrane protein	The dominant conditioning agent of apoptotic cell death. The displaying of microscler shape cell death check that to suppress son active, short isoform has then promoted apoptosis. BCL2L1 is by mitochondrial and electronics of regulation and control and the homeostasis raising cell survival rate relevant with infiltration.
				BID	The interactional death domain activator of BH3-		Induce ice sample protease and Apoptosis. The protective effect (passing through similitude) of antagonism bcl-2. Coding and activator (BAX) or antagonist (BCL2) form the new death agonist of heterodimer.

Symbol	Title	Classification	Describe
				BIK	BCL2-interaction inhibitor		Accelerated apoptosis. Suppress this with the combination of apoptosis repressor BCL2L1, bhrf1, BCL2 or adenovirus homologue e1b 19k protein and promoted dead activity.
BIRC2	The 2 type baculoviral IAP that contain repeated fragment	The apoptosis repressor	Can suppress apoptosis by the required signal of regulation and control activation ICE sample protease. Interact with TRAF1 and TRAF2. Cytoplasmic
				BIRC3	The 3 type baculoviral IAP that contain repeated fragment	The apoptosis repressor	The apoptosis repressor. Interact with TRAF1 and TRAF2. Cytoplasmic
BIRC5	The 5 type baculoviral IAP that contain repeated fragment	The apoptosis repressor	AKA Survivin; API4: may offset the default effect of bringing out cell cycle G2/M phase apoptosis, during apoptosis, be related with the microtubule of mitotic spindle.
				BSG	Basignin	Signal conduction peripheral blood serous coat albumen	The immunoglobulin superfamily member, the clostridiopetidase A stimulating factor in tumour cell source stimulates the synthetic of fibroblast mesostroma metalloproteinases.

Symbol	Title	Classification	Describe
				BPI	Sterilization/the raising sterilization/infiltrative protein-	The embrane-associated protein enzyme	LPS has cytotoxicity in conjunction with albumen to many gram-negative biologicals, finds in bone marrow cell

Symbol	Title	Classification	Describe
				C1QA	Complement component	1, q subfraction, α polypeptide	Protease/protease inhibitors	The SC system forms the C1 compound with proenzyme c1r and c1s.
CALCA	Calcitonin/calcitonin n polypeptide of being correlated with, the α type	The conduction of cell signal and activation	AKA CALC1 promotes that calcium is absorbed in the bone fast.
				CASP1	Caspase	1	Protease	Activate IL1B, the irritation cell apoptosis
CASP3	Caspase
		3	Protease/protease inhibitors	The cascade reaction that relates to the caspases activation that causes apoptosis, cutting CASP6, CASP7, CASP9
CASP9	Caspase
		9	Protease	Be combined with APAF1 and activate, cutting also activates CASP3
CCL3	Chemotactic factor (CF) (C-C motif) part 3				Cell factor-chemotactic factor (CF)-growth factor	AKA: α-MIP1, with the monokine that CCR1, CCR4 and CCR5 are combined, the main HIV inhibiting factor that cd8 cell produces
		CCNA2	Cyclin A2	Cyclin			Promote G1/S and the cell cycle of G2/M phase, interact with cdk2 and cdc2.

Symbol	Title	Classification	Describe
				CCNB1	Cyclin B1	Cyclin	Drive the cell cycle in the G2/M phase, be compounded to form mitosis with cdc2 and promote the factor
CCND1	Cyclin D1	Cyclin	At G1/S (initial) phase cell cycle regulation, interact with cdk4 and cdk6, have the oncogene function

Symbol	Title	Classification	Describe
				CCND3	Cyclin D3	Cyclin	Drive the cell cycle in the G1/S phase, express increase and keep the trend of raising in the S phase in the G1 phase after a while, interact with cdk4 and cdk6
CCNE1	Cyclin E1	Cyclin	The driving cell cycle changes at G1/S, and it is active that the main downstream target of CCND1, S phase centerbody copy required cdk2-CCNE1, interacts with RB
				CCR1	Chemotactic factor (CF) (C-C motif) acceptor 1	Chemokine receptors	A member of β chemokine receptors family (7 transmembrane proteins). With SCYA3/MIP-1a, SCYA5/RANTES, MCP-3, HCC-1,2 and 4 and the MPIF-1 combination. At dendritic cells in inflammation site migration and work in monocytic the raising.
CCR3	Chemotactic factor (CF) (C-C motif) acceptor 3	Chemokine receptors	C-C type chemokine receptors (Eotaxin acceptor) thus in conjunction with calcium current in Eotaxin, Eotaxin-3, MCP-3, MCP-4, SCYA5/RANTES and the mip-1 δ mediated cell. Perhaps form the co-receptor that HIV-1 infects with CD4. Relate to eosinophilic raising. Th2 cell chemotactic factor acceptor on main.
				CCR5	Chemotactic factor (CF) (C-C motif) acceptor 5	Chemokine receptors	The member of β chemokine receptors family (7 transmembrane proteins). Be combined with SCYA3/MIP-1a and SCYA5/RANTES. By T cell and Expression of Macrophages, be a kind of important co-receptor for the macrophage tropic virus that comprises HIV passes through host cell. In the Th1 cell migration, work. The defective of this allele gene is relevant with HIV infection resistance.
CD14	CD14 antigen	Cell sign	LPS acceptor as the monocyte sign
				CD19	CD19 antigen	Cell sign	AKA Leu12; Bcell growth factor
CD34	CD34 antigen	Cell sign	AKA: hematopoiesis initiator cell antigen. Optionally be expressed in the cell surface antigen on the artificial blood initiator cell. The endothelial cell sign.

Symbol	Title	Classification	Describe
				CD3Z	CD3 antigen, the ζ polypeptide	Cell sign	T cell surface glycoprotein
CD4	T4 antigen (p55)	Cell sign	The helper T-cell sign
				CD44	CD44	Cell sign	The cell surface receptor of hyaluronate. May relate to matrix adhesion, lymphocyte activation and lymph node self-aiming.
CD86	CD 86 antigens (cD 28 antigen parts)	The conduction of cell signal and activation	AKA B7-2, the memebrane protein that finds in bone-marrow-derived lymphocyte and monocyte by the generation of IL-2, is the necessary costimulatory signal of T lymphopoiesis.
				CD8A	CD8 antigen, the α polypeptide	Cell sign	Inhibitor T cell sign
CDH1	Cadherin
1,1 type, the E-cadherin	Cell-cell adherence/interaction		AKA ECAD, UVO: the calcium ion dependent form cell adhesion molecule of mediated cell and cell interaction in epithelial cell
		CDH2		Cadherin
	2,1 types, the N-cadherin	Cell-cell adherence/interaction	AKA NCAD, CDHN: the calcium dependent form glycoprotein of mediated cell-cell-cell interaction may relate to the neuron recognition mechanism
cdk2				Cyclin dependent form kinases 2	Kinases	Relevant with cyclin A, D and E, the highest in S phase and G2 phase activity, the cutting of the CDK inhibitor by caspase mediation, the activation of CDK2 may help the apoptotic process after the caspase activation

Symbol	Title	Classification	Describe
				cdk4	Cyclin dependent form kinases 4	Kinases	Cause cdk4 and the cyclin-D type compound of cell proliferation in the G1 phase, suppressed by CDKN2A (p16)
CDKN1A	Cyclin-dependent form inhibitors of kinases 1A (p21)	The tumour inhibitor	May in conjunction with and suppress cyclin dependent form kinase activity, prevent the key cyclin dependent form kinase substrate phosphorylation and block cell cycle progression, activated tumour inhibitor function by p53
				CDKN2A	Cyclin dependent form inhibitors of kinases 2A	Cell cycle regulation and control-tumour inhibitor	AKA p16, MTS1, INK4: relate to the tumor suppressor gene of various malignant tumours, attract normal double somatocyte late period at G1
CDKN2B	Cyclin-dependent form inhibitors of kinases 2B (p15)	The tumour inhibitor	Pretend usefulness with cdk4 and cdk6, in the growth regulation and control, work, but limited as the effect of tumour inhibitor
				CHEK1	The outpost of the tax office, schizosaccharomyces pombe		Relating to the cell cycle that dna damage occurs or occurring when not connecting DNA stops, and prevents the activation of cdc2-cyclin b compound
CLDN14	Claudin
		14		AKA DFNB29 closely engages the constituent of chain
COL1A1	Collagen, 1 type, α 1				Tissue remodeling	The AKA procollagen, extracellular matrix albumen relates to the fibrillatable process that is subjected to liver injury.
		COL7A1	The VII Collagen Type VI, α 1	Collagen differentiation extracellular matrix			α	1 subunit of VII Collagen Type VI can make collagenous fibrils connect with basilar memebrane
CRABP2	Cellular retinoic acid binding protein				Biostearin binding signal conduction-transcriptional control	The low molecular weight protein of high expressed in skin, it is important being considered to grow and break up in the regulation and control at the skin of RA mediation
		CRP	C reactive protein	Acute phase protein			Acute phase protein

Symbol	Title	Classification	Describe
				CSF2	Granulocyte-monocyte colony stimulating factor	Cell factor-chemotactic factor (CF)-growth factor	AKA GM-CSF, hemopoieticgrowth factor stimulates growth and differentiation from the hematopoiesis precursor of a plurality of kinds of systems, comprises granulocyte, macrophage, eosinocyte and red blood cell
CSF3	Colony stimulating factor 3 (granulocyte)	Cell factor-chemotactic factor (CF) growth factor	AKA GCSF regulates and control granulocytic generation differentiation and function
				CTGF	CTGF	IGF-break up-be subjected to traumatic response	Be included in growth factor and induce the serum of rear expression to bring out front early gene product interior peptide family member, excessively be expressed in the disorderly disease of fibre modification
CTNNA1	Catenin, α 1	Cell adherence	Be connected with actin cytoskeleton in conjunction with cadherin and with them
				CX3CR1	Chemotactic factor (CF) (C-X3-C) acceptor 1	Chemokine receptors	CX3CR1 is HIV co-receptor and the white blood cell chemotactic/adhesion acceptor of fractalkine. Natural killer cell is all significantly expressed CX3CR1 in migration with in adhering to and fractalkine is responded.
CXCR4	Chemotactic factor (CF) (C-X-C motif), acceptor 4 (fusin)	Chemokine receptors	The acceptor of Gro-beta-T SDF1. With the co-receptor of CD4 as lymphocyte torrid zone HIV-1 virus. In B cell, Th2 cell and originally T cell migration, work.
				CYP1A1	Cytochrome P450 1A1	The metabolism enzyme	The polycyclic aromatic hydrocarbon metabolism, monooxygenase
CYP1A2	Cytochrome P450 1A2	The metabolism enzyme	The polycyclic aromatic hydrocarbon metabolism, monooxygenase
				CYP2C19	Cytochrome P450 2C19	The metabolism enzyme	The xenobiotics metabolism, monooxygenase

Symbol	Title	Classification	Describe
				CYP2D6	Cytochrome P450 2D6	Metabolic enzyme	The xenobiotics metabolism, monooxygenase
CYP2E	Cytochrome P450 2E1	Metabolic enzyme	The xenobiotics metabolism, monooxygenase, catalysis comes the from childhood formation of the reaction intermediate of organic molecule (being ethanol, acetaminophen, carbon tetrachloride)
				CYP3A4	Cytochrome P450 3A4	Metabolic enzyme	The xenobiotics metabolism, widely catalysis specificity, the liver P450 of abundant expression
CXCL10	Chemotactic factor (CF) (C-X-C motif) part 10	Cell factor-chemotactic factor (CF) growth factor	AKA: γ IP10, but interferon inducing cell factor IP10, SCYB10, the part of CXCR3 in conjunction with the stimulation that has caused monocyte NK cell, brings out the T cell migration
				DAD1	The protector of anti-cell death	Memebrane protein	The trigger cell accent of losing of DAD1 albumen is died
DC13	DC13 albumen		Unknown Function
				DFFB	Dna fragmentation factor, 40-KD, β subunit	Nuclease	Induce dna fragmentation and chromatin are concentrated during accent is died, and can be activated by CASP3
DSG1	Desmoglein
		1	Memebrane protein	Relate to the calcium of the plaque protein of mediated cell-intercellular adhesion and middle filamentous interphase interaction in conjunction with transmembrane glycoprotein. Interact with cadherin.
DTR	Diphtheria toxin acceptor (Heparin-binding epidermal growth factor-like growth factor)				The conduction of cell signal, mitogen	Be considered to relate to the macrophage of mediated cell propagation. DTR is effective mitogen and chemotactic factor (CF) for fibroblast and smooth muscle cell, but for endothelial cell and Yan Bushi.
		DUSP1	The dual specificity phosphatase enzyme	Oxidative stress is replied-tyrosine phosphatase			Bring out in the HSF by oxidation/heat stress and growth factor, make map kinase erk2 dephosphorylation, may in cell proliferation, play the negative regulation effect
ECE1	Endothelin converting Enzyme 1				Metalloproteinases	Large endothelin 1 is cut into endothelin 1
		EDN1	Endothelin	1			Peptide hormone	AKA ET1, endothelium source peptide, strong vasoconstrictor

Symbol	Title	Classification	Describe
				EDR2	Early development conditioning agent 2		Exceptional function in people's cell is not also determined. But may be the part of the compound of regulatory transcription in embryonic development.
EGR1	Early growth reaction 1	Transcription factor	AKA NGF1A regulates transcribing of the gene that relates in mitosis and the differentiation

Symbol	Title	Classification	Describe
				ELA2	Elastoser	2, neutrophil cell	Protease	Modify NK cell, monocyte and granulocytic function
EPHX1	EH 1, microsome (xenobiotics)	Metabolic enzyme	The catalytic reaction epoxides is hydrolyzed into water-soluble dihydrodiol
				ERBB2	V-erb-b2 erythroblast leukemia virus oncogene homologue 2	Oncogene	Oncogene, the taxol resistance that causes breast cancer is expressed in crossing of ERBB2. Belong to EGF tyrosine kinase receptor family. With the gp130 subunit of IL6 dependent form mode in conjunction with the IL6 acceptor. IL6 solvent by MAP kinase pathways conducted signal.
ERBB3	V-erb-b2 erythroblast leukemia virus oncogene homologue 3	Oncogene	Oncogene. Cross and be expressed in the mammary tumor. Belong to EGF tyrosine kinase receptor family. Be activated by neuregulin and ntak combination.
				ESR1	ERs	1	Acceptor/transcription factor	ESR1 by for hormone in conjunction with, DNA combination with transcribe the part activating transcription factor that several very important domains of activation form.
F3	F3	Enzyme/reductant-oxidant	The AKA factor I, clotting factor 3, the cell surface glycoprotein of responsible blood coagulation catalytic action
				FADD	Relevant with Fas (TNFRSF6) by death domain	Co-receptor	Raise the apoptosis adapter molecule that caspase-8 or caspase-10 activate fas (cd95) or tnfr-1 acceptor, this brings out dead signal conduction compound and has finished the proteoclastic activation of CASP8

Symbol	Title	Classification	Describe
				FAP	Fibroblast activation protein matter	The healthy indication of liver	Be expressed in cancer matrix and wound healing place
FCGR1A	The Fc fragment of lgG, high-affinity receptor IA	Memebrane protein	The membrane receptor of CD64 is found in monocyte, macrophage and neutrophil cell
				FGF18	FGF-18	Growth factor	Relate to various biological processes, comprise that reparation, tumor growth and intrusion occur, organize for embryonic development, Growth of Cells, form
FGF7	Fibroblast growth factor 7	Growth factor-break up-conducted by traumatic response-signal	Aka KGF, epithelial effective mitogen is brought out after skin is impaired

Symbol	Title	Classification	Describe
				FLT1	The Fms-EGFR-TK 1 (VEGF/vascular permeability factor acceptor) of being correlated with		AKA VEGFR1; FRT; Vegf receptor relates to blood vessel growth and vascular permeability regulation and control
FN1	Fibronectin	Cell adherence-motility-signal conduction	Many fibroblastic main cell surface glycoproteins, being considered to has effect in cell adherence, morphology, wound healing and cell mobility
				FTL	Ferritin, the light polypeptide	The iron intercalating agent	In the cell, iron is stored albumen
FOLH1	The folic acid hydrolase	Hydrolase	AKA PSMA, GCP2: at normal and prostate tumor cells, film is in conjunction with glycoprotein, is hydrolyzed folic acid and is that N-acetylation a-connects acid dipeptidase
				FOS	V-fos FBJ Mouse Bone sarcoma oncogene homologue	Transcription factor-inflammatory reaction-Growth of Cells and keeping	With the initial proto-protein that JUN works, transcribe at AP-1 regulatory site stimulated gene, FOS expresses relevant with apoptotic cell death in some cases

Symbol	Title	Classification	Describe
				G6PC	G-6-Pase, catalytic	G-6-Pase/glycogen metabolism	Final step in catalysis gluconeogenesis and the glycogen decomposition approach. Be subjected to the glucocorticoid stimulation and suppressed by force by insulin. . cross expression (uniting expression with PCK1) and cause hepatic glucose output to increase
GADD45A	The α type can induce growth to stop and dna damage	The cell cycle-DNA reparation-apoptosis	Be induced to transcribe after processing at urgent growth stop condition with the dna damage agent, and affect it and be combined with the interactional PCNA of some cell division protein kinase
				GCG	Hyperglycemic factor	Pancreas/peptide hormone	Pancreatic hormone is by stimulating the effect that reduces glucose in glycogen decomposition and the gluconeogenesis with insulin. Preferred hyperglycemic factor is low expresses. The glucagon-like peptide (GLP-1) that is proposed for diabetes B people treatment has suppressed hyperglycemic factor.
GCGR	The hyperglycemic factor acceptor	The hyperglycemic factor acceptor	The expression of GCGR is reduced by force by glucose. Lack or unbalanced may in NIDDM, working. The possible target that has been considered to gene therapy.

Symbol	Title	Classification	Describe
				GFPT1	Glutamate-fructose-6-phosphate transaminase 1	The glutamate aminopherase	Glucose enters the rate-limiting enzyme of aminohexose biosynthesis pathway (HBP). GFA cross expressing in muscle and adipose tissue increased the product (may pass through the glucose defective) of the HBP that is considered to cause insulin resistance
GJA1	The breach adaptor protein, α Isosorbide-5-Nitrae 3kD		AKA CX43, the protein component of breach combination, the key component that breach engages in the heart may be very important in synchronously heart contracting and embryonic development

Symbol	Title	Classification	Describe
				GPR9	G protein coupled receptor 9	Chemokine receptors	The CXC chemokine receptors is combined with SCYB10/IP-10, SCYB9/MIG and SCYB11/I-TAC. The combination of chemotactic factor (CF) and GPR9 causes integrin activation, cytoskeleton to change and chemotaxis moves. Significantly be expressed in the effector/memory T cell of external cultivation and in the Th1 cell migration, work.
GRO1	The GRO1 oncogene (melanoma growth-stimulating activity, α)	Cell factor-chemotactic factor (CF)-growth factor	AKA SCYB1; The chemotaxis of neutrophil cell
				GRO2	The GRO2 oncogene	Cell factor-chemotactic factor (CF)-growth factor	AKA MIP2, SCYB2; Macrophage inflammatory protein by monocyte and neutrophil cell generation
GSR	Glutathione reductase	1	Oxidoreducing enzyme					AKA GR; GRASE; Keep high-caliber reductive glutathione in the cytosol
				GST	Glutathione S-transferase	Metabolic enzyme	The catalysis glutathione be combined with metabolism substrate form more water misciblely secrete compound, to the nonspecific primer-probe of all members of GST family pair
GSTA1   And A2	Glutathione S-transferase 1A1/2	The metabolism enzyme	The catalysis glutathione is combined with metabolism substrate and is formed the more water miscible compound of secreting

Symbol	Title	Classification	Describe
				GSTM1	Glutathione S-transferase M1	Metabolic enzyme	The catalysis glutathione is combined with metabolism substrate and is formed the more water miscible compound of secreting
GSTT1	Glutathione S-transferase, θ 1	Metabolism	Catalytic reduction type glutathione engages with widely external source and endogenous hydrophobic electrophilic reagent, plays an important role in people's carcinogenesis

Symbol	Title	Classification	Describe
				GYS1	Glycogensynthase 1 (muscle)	Transferase/glycogen metabolism	The key enzyme of the synthetic regulation and control of glycogen in people's skeletal muscle. Usually be subjected to insulin stimulating, but GS demonstrates complete anti-insulin stimulation (activity and activation in the muscle are descended) in the NIDDM individuality
GZMB	Granzyme B	Protease/protease inhibitors	AKA CTLA1, the cell mediated immune response lysis that hits is necessary. For inducing fast the target cell apoptosis most important by cytotoxic T cell. The interactional inhibition of GZMB-IGF2R (GZMB acceptor) has stoped bringing out of the combination of GZMB cell surface, absorption and apoptosis.
				HIF1A	But hypoxgia inducible factor 1, the α subunit	Transcription factor	AKA MOP1, ARNT interaction albumen, transcribing of mediation oxygen related gene brought out by hypoxgia
HK2	Hexokinase
		2	Hexokinase	Glucose phosphate is changed into G-6-P salt. It is the lower HK2 activity that is caused by insulin resistance that NIDDM patient has possibility. Effect to GCK is similar.
HLA-DR   B1	Main Tissues compatibility compound, II type, DR β 1				Histocompatbility	Conjugated antigen is and is handed to the CD4+ cell
		HMGIY	High movement property protein, I and Y isoform	DNA is in conjunction with transcriptional control-oncogene			The latent carcinoma gene that has the MYC binding site in the promoter zone relates to and containing or very near the transcriptional control of the gene of a+t enrichment region

Symbol	Title	Classification	Describe
				HMOX1	Heme oxidase (unlinking) 1	Enzyme/reductant-oxidant	Endotoxin can be induced
HSPA1A	Heat shock protein 70	The conduction of cell signal and activation	Heat shock protein 70 kDa; Molecular chaperones is stablized rich AU mRNA
				ICAM1	Thin Intercellular adhesion molecule 1	Cell adherence/stroma protein	Endothelial cell surface molecule, regulating cell adhere to and circulation, are not regulated and control at the cell factor stimulating course
IFI16	But IFN-γ inducible protein 16	The conduction of cell signal and activation	Transcription repression
				IFNA2	Interferon, α 2	Cell factor-chemotactic factor (CF)-growth factor	Produced the interferon of tool antivirus action by macrophage
IFNG	IFN-γ	Cell factor/chemotactic factor (CF)/growth factor	The anti-inflammatory activity of urging to become reconciled, the TH1 cell factor, the nonspecific inflammation medium is produced by the T cell of activation
				IGF1R	The type-1 insulin like growth factor acceptor	Cell factor-chemotactic factor (CF)-growth factor	DNA is synthetic for the mediation insulin stimulating, and mediation IGF1 stimulates cellular proliferation and breaks up
IGFBP3	Insulin-like growth factor binding protein 3		AKA IBP3 is expressed by vascular endothelial cell, may affect the IGF activity
				IL10	IL-10	Cell factor-chemotactic factor (CF)-growth factor	Anti-inflammatory, TH2 suppresses the generation of proinflammatory cytokine

Symbol	Title	Classification	Describe
				IL12B	Interleukin	12 p40	Cell factor-chemotactic factor (CF)-growth factor	Short scorching, the medium of natural immunity, the TH1 cell factor need to stimulate altogether with IL-18 and induce IFN-g

Symbol	Title	Classification	Describe
				IL13	Interleukin-11 3	Cell factor/chemotactic factor (CF)/growth factor	Suppressing the inflammatory cell factor produces
IL15	Interleukin	15	Cell factor/chemotactic factor (CF)/growth factor					Short scorching, the activation of mediation T cell suppresses apoptosis, with IL-2 co-induction IFN-g and TNF-a
				IL18	Interleukin	18	Cell factor-chemotactic factor (CF)-growth factor		Short scorching, TH1, congenital and acquired immunity promotes apoptosis, need to be total to spread effect to induce the TH1 cell factor in T and the NK cell with IL-1 or IL-2
IL18BP	IL-18BP	Cell factor-chemotactic factor (CF)-growth factor	The inhibitory action that relates to early stage TH1 cell factor reaction
				IL18RI	Interleukin-11 9 acceptors 1	Memebrane protein	The interleukin 18 acceptor causes NFKB-B activation in conjunction with activator, belongs to IL1 family but not in conjunction with IL1A or IL1B.
ILIA	Interleukin-11, α	Cell factor-chemotactic factor (CF)-growth factor	Short scorching, composition type and inducible expression are in various kinds of cell. Usually only kytoplasm release during serious inflammation
				IL1B	Interleukin-11, β	Cell factor-chemotactic factor (CF)-growth factor	Short scorching, composition type and inducible expression are in many cell types, and be secreted.

Symbol	Title	Classification	Describe
				IL1R1	Interleukin	1 receptor, the I type	The conduction of cell signal and activation	AKA:CD12 or IL1R1RA are in conjunction with triformed il-1 (IL1A, IL1B and IL1RA). The combination of activator causes the NFKB activation.
IL1RN	The interleukin-11 receptor antagonist	Cell factor/chemotactic factor (CF)/growth factor	The IL1 receptor antagonist, anti-inflammatory does not stimulate IL-1 sample activity to suppress the combination of IL-1 and IL-1 acceptor by being combined with acceptor
				IL2	Interleukin-22	Cell factor/chemotactic factor (CF)/growth factor	The T-Porcine HGF, by the T cellular expression of activation, regulation and control lymphocyte activation and differentiation suppress apoptosis, the TH1 cell factor
IL4	IL-4	Cell factor/chemotactic factor (CF)/growth factor	Anti-inflammatory, TH2 suppresses proinflammatory cytokine, increases the expression of IL-1RN, regulates and control lymphocytic activation
				IL5	Interleukin-15	Cell factor/chemotactic factor (CF)/growth factor	The eosinocyte stimulating factor, stimulation B Cell Differentiation in late period is with secretion Ig

Symbol	Title	Classification	Describe
				IL6	Interleukin 6 (interferon, β 2)	Cell factor-chemotactic factor (CF)-growth factor	Short inflammation and anti-inflammatory activity, TH2 cell factor, the activation of regulation and control hemopoietic system and innate response
IL8	Interleukin 8	Cell factor-chemotactic factor (CF)-growth factor	Short scorching, main secondary inflammatory mediator, cell adherence, signal transduction, cell-cell signal conduction, Angiogenesis, synthetic by the cell of wide range of types
				INS	Insulin	The insulin receptor aglucon	Reduce blood sugar concentration and accelerate the synthetic of glycogen in the liver. Z is unlike among the IDDM so important in NIDDM.

Symbol	Title	Classification	Describe
				IRF5	Interferon regulatory factor 5	Transcription factor	By dna sequence dna specificity transcribing in conjunction with the regulation and control interferon gene. Different effects comprises the activation of virus-mediated interferon, and the modulation of Growth of Cells, differentiation, apoptosis and immune system activity.
IRS1	Substrate	1	Signal conduction/transmembrane receptor protein matter					The just regulation and control of insulin effect. When insulin be combined with insulin receptor-this albumen is activated during in conjunction with the 85-kDa subunit of PI 3-K. In the skeletal muscle of obesity group, reduce.
				ITGAM	Integrin, α M, complement receptors	Integrin	AKA, complement receptors, 3 types, the α subunit, neutrophil cell adheres to acceptor, plays the activation endothelial cell in neutrophil cell and monocytic adhesion.
IVL	The involucrum involucre	Structural proteins-peripheral blood serous coat albumen	The component of keratinocyte cross linking membrane at first comes across by in the crosslinked cytosol of TGase and memebrane protein
				JUN	V-jun Avian sarcoma virus 17 oncogene homologues	DNA is in conjunction with transcription factor	Initial proto-protein, directly and the component of the transcription factor AP-1 of target DNA sequence interaction regulate gene expression
KAI1	Kangai1	The tumour inhibitor	AKA SAR2, CD82, ST6: prostate cancer cell transfer ability inhibitor
				K-ALPH   A-1	The α tubulin, ubiquity	The microtubule peptide	The key component of microtubule is in conjunction with 2 molecule GTP

Symbol	Title	Classification	Describe
				KITLG	The KIT part	Growth factor	AKA stem cell factor (SCF); Columnar cell's growth factor relates to the cystic fibrosis that chronic hepatitis causes/sclerosis
KLK2	Kallikrein
		2, prostatic	Protease-kallikrein	AKA hGK-1: the gland kallikrein, express mainly being confined to prostate.

Symbol	Title	Classification	Describe
				KLK3	Kallikrein	3	Protease-kallikrein	AKA PSA: the kallikrein sample protease that usually in semen liquefaction, plays a role. In prostate cancer, increase.
KRT14	Keratin	14	Structural proteins-differentiation-cellular morphology						I type keratin, relevant with keratin 5, the component of intermediateness filamentous, several autosomal dominant blister dermatoses that caused by gene defect;
				KRT16	Keratin	16	Structural proteins-differentiation-cellular morphology	I type keratin, the component of intermediateness filamentous is brought out to help to strengthen in skin disease and is bred or abnormal differentiation
KRT19	Keratin
		19	Structural proteins-differentiation	AKA K19:I type Epidermal Keratin, filamentous in the middle of may forming
KRT5	Keratin				5	Structural proteins-differentiation	AKA EBS2: with the II type keratin of the 58kD of I type keratin coexpression in the layering epithelium of 50kD. The expression of KRT5 is the active Keratinocytic characteristics of mitosis and is the primary structure component of filamentous in the middle of the mitosis epidermis base portion cell 10nm.
		KRT8	CK8	Structural proteins-differentiation				AKA K8, CK8:II type keratin, with the Keratin 18 coexpression, the formation of filamentous in the middle of relating to
LGALS3	Lectin, solvable in conjunction with galactoside, 3				The healthy indication of liver	AKA galectin	3; The Growth of Cells regulation and control
		LGALS8	Lectin, solvable in conjunction with galactoside, 8	Cell adherence-growth and differentiation				AKA PCTA-1: be combined with the β galactoside, relate to biological processes such as cell adherence, Growth of Cells regulation and control, inflammation, immune modulation, apoptosis and transfer
LBP	Lipopolysaccharide binding protein				Memebrane protein	Acute phase protein, on lipid in conjunction with the memebrane protein of a part of bacterium LPS

Symbol	Title	Classification	Describe
				MADD	MAP-kinase activation death domain	Accessory receptor	Relevant with TNFR1 by the interaction between death domain-death domain, MADD cross to express the expression that has activated map kinase ERK2 and MADD death domain stimulated ERK2 and JNK1MAP kinases the two and induced the phosphorylation of kytoplasm Phospholipase A2
MAP3K1
	4	The protein kinase kinase kinases 14 that mitogen activates	Kinases	The NFKB1 activator
MAPK1					The protein kinase 1 that mitogen activates	Transferase	AKA ERK2 can promote to enter the cell cycle, and growth factor is responded

Symbol	Title	Classification	Describe
				MAPK8	The protein kinase 8 that mitogen activates	Kinases-coerce and reply-the signal conduction	Aka JNK1, the protein kinase that mitogen activates, regulation and control c-Jun response cell is coerced, and the UV irradiation of skin activates MAPK8
MDM2	Mdm2, two minutes 2, p53 of the 3T3 cell that is converted are in conjunction with albumen	Oncogene/transcription factor	The cell cycle of suppressing p53-and p73-mediation by being combined with its transcriptional activation domains stops, and causes tumour to occur. Allow the output of p53 nuclear and it is oriented to the proteolysis of proteasome mediation.
				MIF	Macrophage migration inhibitory factor	The conduction of cell signal and growth factor	AKA; GIF; Lymphokine, the regulation and control macrophage that plays a role by the anti-inflammatory effect that suppresses glucocorticoid.
MMP1	Matrix metallopeptidase	1	Protease/protease inhibitors					The Aka clostridiopetidase A, cutting I-III Collagen Type VI, under normal and disease two states, occur reinvent in play a crucial role, be subjected to the transcriptional control of growth factor, hormone, cell factor and cell transformation
				MMP2	MMP2	Protease/protease inhibitors	The Aka gelatinase, cutting IV, V, VII Collagen Type VI and I type gelatin are produced by normal skin fibroblast, can work in modulating vascular generation and inflammatory reaction

Symbol	Title	Classification	Describe
				MMP3	MMP3	Protease/protease inhibitors	AKA stromelysin; Degraded fibronectin, laminin and gelatin
MMP9	GELB	Protease/protease inhibitors	AKA gelatinase B, the degraded extracellular matrix molecules is secreted by the neutrophil cell that IL-8 stimulates
				MP1	Metalloproteinases	1	Protease/protease inhibitors	The member of pitrilysin family. A kind of metal endoproteinase. In general cell regulation and control, play widely effect.
MRE11A	Meiotic recombination (saccharomyces cerevisiae) 11 homologue A	Nuclease	Relate to the exonuclease that the dna double chain breaks and repairs
				MYC	V-myc bird myelocytomatosis viral oncogene homologue	Transcription factor-oncogene	Promote the transcription factor of cell proliferation and conversion by activating the gene that promotes growth, may go back suppressor and express
N33	The prostate cancer tumour inhibitor of generally acknowledging	The tumour inhibitor	Complete memebrane protein. Relevant with the homotype disappearance in the metastatic prostate cancer.

Symbol	Title	Classification	Describe
				NFKB1	The nuclear factor (p105) of к light chain polypeptide genetic enhancer in the B cell 1	Transcription factor	P105 is the precursor of the p50 subunit of nuclear factor NFKB, is combined with the common sequence of к-b that is positioned at immune response and acute phase response and relates to the enhancing subarea of gene, and this precursor is not in conjunction with DNA self.
NFKBIB	The nuclear factor of к light chain polypeptide genetic enhancer in the B cytostatics, β	Transcribe and regulate son	The activity that suppresses/regulate the NFKB compound by the NFKB in the trapping kytoplasm. Thereby the serine residue sign NFKBIB albumen of phosphorylation is suitable for division activates the NFKB compound.

Symbol	Title	Classification	Describe
				NOS1	Nitricoxide synthase 1 (neuronic)	Enzyme/reductant-oxidant	From L-arginine and the synthetic nitric oxide of molecular oxygen, the contraction of regulation and control skeletal muscle blood vessel, isohydria, neuroendocrine physiology, smooth muscle movement and sexual function
NOS2A	Nitricoxide synthase 2A	Enzyme/reductant-oxidant	AKA iNOS produces sterilization/tumoricidal NO
				NOS3	Nitricoxide synthase	3	Enzyme/reductant-oxidant	The enzyme of finding in the endothelial cell of mediation smooth muscle contact promotes blood coagulation by the blood platelet activation.
NR1I2	Nuclear receptor subunit family 1	Transcribe activation factor-signal conduction-xenobiotics metabolism	Aka PAR2, the nuclear hormone receptor family member of part activating transcription factor, the transcribing of active cell pigment P-450 gene
				NR1I3	Nuclear receptor subunit family 1, I type, family 3	Metabolism acceptor/transcription factor	AKA β composition type androstane acceptor (CAR) has formed nuclear factor with the heterodimer of biostearin X acceptor, mediation; The P450 of phenobarbital-sample derivant induces.
NRP1	Neuropilin	1	Cell adherence					AKA NRP, VEGF165R: regulation and control VEGF and KDR (vegf receptor) combination and bioactive a kind of new vegf receptor subsequently, and therefore may regulate the Angiogenesis that VEGF-induces, the calcium self cell adhesion molecule that during the touring formation of some neuron, works
				ORM1	Acid seromucoid 1	The healthy indication of liver	AKA alpha1 Acid glycoprotein (AGP), acute stage inflammatory protein
OXCT	3-ketone acid CoA transferase	Transferase	The reversible transfer of OXCT catalysis coacetylase from succinyl-coenzyme A to acetoacetate is as the first step of extrahepatic tissue ketolysis (ketoboidies utilization).

Symbol	Title	Classification	Describe
				PART1	The prostate androgen is regulated transcript 1		In the LNCaP cell, increase by being exposed to present in the androgen to express

Symbol 3	Title	Classification	Describe
				PCA3	Prostate cancer antigen 3		AKA DD3: prostate is special, and high expressed is in tumor of prostate
PCANAP
	7	Prostate cancer GAP-associated protein GAP 7		AKA IPCA7: Unknown Function, with known prostate cancer gene co-expressing
PCK1					Phosphoenolpyruvate carboxylate carboxylic kinases 1	Speed limit gluconeogenesis enzyme	Gluconeogenesis rate-limiting enzyme-in hepatic glucose output regulation and control, play a crucial role by insulin and hyperglycemic factor. Crossing in liver expressed and caused the synthetic hepatic glucose candy output of antagonism hyperglycemic factor and liver insulin output to increase
	PCNA	PCNA	DNA combination-dna replication dna-DNA reparation-cell proliferation	Dna replication dna and reparation all need, the factor of advancing of DNA polymerase delta and e
PCTK1					PCTAIRE protein kinase 1		The SER/THR family that belongs to protein kinase, the CDC2/CDKX subfamily. Work in the signal transduction cascade reaction of noble cells endways.
	PDCD8	Apoptosis 8 (inducing the factor of apoptosis)	Enzyme, reductase	Cause the main mitochondria factor of nuclear apoptosis. Be independent of outside the caspase apoptosis.
PDEF					Prostatic epithelium specificity Ets transcription factor	Transcription factor	As the androgen self transcriptional activation agent of PSA promoter, DNA binding structural domain direct and androgen receptor interacts and strengthens androgen mediated PSA promoter activation
	PF4	Platelet factor 4 (SCYB4)	Chemotactic factor (CF)	PF4 is released to during the platelet aggregation and is neutrophil leucocyte and monocytic chemotactic factor (CF). The heparin-like molecule on during the main physiological role of PF4 shows as and blood vessel endothelium surface, thus suppress local Antithrombin III activity and promote blood coagulation
PI3					The protease inhibitors 3 of skin-derived	Protease inhibitors-protein bound-extracellular matrix	Aka SKALP is found in the protease inhibitors in several inflammatory skin diseases, and its expression can be used as dermopathic sign

Symbol	Title	Classification	Describe
				PIK3R1	Phosphoinositide-3-kinases, regulation and control subunit, polypeptide 1 (p85 α)	Regulatory enzyme	The just regulation and control of insulin effect. Rest among IRS albumen and the Gab1-activity is that the GLUT of insulin stimulating shifts and glucose uptake activates needed to plasma membrane.
PLA2G7	Phospholipase A2, VII type (platelet-activating factor acetylhydrolase, blood platelet)	Enzyme/reductant-oxidant	Platelet activating factor
				PLAT	Tissue-type plasminogen activator	Protease	AKA TPA is transformed into fibrinolysin with plasminogen, relates to fibrinolysis and cell migration
PLAU	Urokinase type plasminogen activator	Protease/protease inhibitors	AKA uPA, cutting plasminogen become fibrinolysin (being responsible for the protease of non-specific extracellular matrix degraded)
				PNKP	Polynucleotide kinase 3 '-phosphatase	Phosphatase	The 5-of catalytic nucleic acid causes phosphorylation and can have relevant 3-that to cause phosphatase active, is expected at DNA behind ionizing radiation or the oxidative damage and plays an important role in repairing
POV1	Prostate cancer is crossed expressing gene 1		Optionally cross the RNA that is expressed in the tumor of prostate sample
				PPARA	Peroxisome proliferator-activated receptor	The metabolism acceptor	In conjunction with agent for peroxisome proliferator (that is, aliphatic acid, blood lipid-lowering medicine) and regulate and control aliphatic acid beta-oxidation reduction approach
PPARG	Peroxisome proliferator-activated receptor, γ	Transcription factor/part dependent form nuclear receptor	The main pharmacology target of insulin resistance treatment in NIDDM. Relate to glucose and fat metabolism in the skeletal muscle.

Symbol	Title	Classification	Describe
				PRKCB1	Protein kinase C, β 1	Protein kinase C/protein phosphorylation	The negative regulation of insulin effect. Activated-increased the phosphorylation of IRS-1 by hyperglycemia and reduced insulin receptor kinase active. The enhancing of PKC activation may cause causing that TGF-β and fibronectin cross the oxidative pressure of expression
PSCA	The prostate stem cell antigen	Antigen	Androgen-dependent type and non-dependent form tumour be the prostate specificity cell surface antigen of strongly expressed all
				PTEN	Phosphatase and tensin homologue (sudden change in multiple late period tumour 1)	The tumour inhibitor	By the tumour inhibitor of negative regulation PI3-kinases/Akt signal pathway adjusting G1 phase cell cycle progression, a common-denominator target of this signal conductive process is cyclin-dependent form inhibitors of kinases p27 (CDKN1B).
PTGIS	Prostacyclin I2 (prostacyclin) synthase	Isomerase	AKA PGIS; PTGI; CYP8; CYP8A1 is transformed into prostacyclin (vasodilator) with prostaglandin h2, Cytochrome P450 family, and the unbalanced of prostacyclin may be caused myocardial infarction, apoplexy, arteriosclerosis
				PTGS2	Prostaglandin-endoperoxide synthase 2	Enzyme/reductant-oxidant	AKA COX2, short scorching, the arachidonic acid family member is used for the prostaglandin transformation way, is induced by proinflammatory cytokine.
PTPRC	Protein tyrosine phosphatase, acceptor type, C	Cell marking	AKA CD45, the activation of mediation T cell
				PTX3	The Pentaxin related gene is induced rapidly by IL-1 β		AKA TSG-14; Similar to pentaxin hypotype inflammation acute phase protein, the new sign of inflammatory reaction.
RAD52	RAD52 (saccharomyces cerevisiae) homologue	The DBP body	Relate to the damaged reparation of dna double chain and reduce division/mitosis restructuring

Symbol	Title	Classification	Describe
				RB1	Retinoblastoma 1 (comprising osteosarcoma)	The tumour inhibitor	The instrumentality of Growth of Cells with E2F-sample transcription factor interaction, the nuclear phosphoprotein matter of tool dna binding activity, takes off acetyl enzyme with histone and is combined and suppresses to transcribe
S100A7	S100 calbindin	7	Calcium combination-epidermal differentiation					The member of calbindin S100 family is positioned to relate to the adjusting of cell cycle progression and differentiation in the kytoplasm and/or nuclear of wide range of types cell, and obvious the mistake expressed in psoriatic's skin injury
				SCYA2	But little inducing cell factor A2	Cell factor/chemotactic factor (CF)	AKA MCF albumen 1 (MCP1); Monocyte recruitement is to injured and infected area, out of control in hepatitis
SCYA3	But little inducing cell factor A3 (MIP1a)	Chemotactic factor (CF)	Raise and activate " monokine " that relates to acute inflammatory condition by polymorphonuclear leucocyte. Main HIV-inhibiting factor by the generation of CD8-positive T cell.
				SCYA5	But little inducing cell factor A5 (RANTES)	Chemotactic factor (CF)	With CCR1, CCR3 with CCR5 is combined and be blood mononuclear cell, memory-type auxiliary cell and eosinophilic chemical attractant. Main HIV-inhibiting factor by the generation of CD8-positive T cell.
SCYB10	But little inducing cell factor subfamily B (Cys-X-Cys), the member 10	Chemotactic factor (CF)	CXC subfamily chemotactic factor (CF). The combination of SCYB10 and acceptor CXCR3/GPR9 has caused the spread effect of monocyte, natural inhibitor and T cell migration and the regulating and controlling effect of adhesion molecule expression. SCYB10 is induced by IFNg and may be crucial medium in the IFNg reaction.
				SDF1	Stromal cell-derived factor-1	Chemotactic factor (CF)	The CXC subfamily that belongs to intercrine family, its activated leukocyte cell. SDF1 is the main part of CXCR4, is the co-receptor of 1 type immune deficiency syndrome virus (HIV-1) with CD4. SDF1 is very effective lymphocyte chemical attractant.

Symbol	Title	Classification	Describe
				SELE	Select albumen E (endothelial adhesion molecule 1)	Cell adherence	AKA ELAM is expressed by the endothelial cell that cell factor stimulates, and has mediated the adhesion of neutrophil cell to the blood vessel internal layer
SERPINB
	5	Serpin, B branch, the member 5	Protease/protease inhibitors/tumour inhibitor	Protease inhibitors, the tumour inhibitor is especially for transfer. Suppress the tumour invasion by suppressing cell mobility.

Symbol	Title	Classification	Describe
				SERPINE   1	Serine (or cysteine) protease inhibitors, B branch (ovalbumin), the member 1	Protease/protease inhibitors	Plasminogen activator inhibitor-1/PAI-1
SFTPD	Surfactant, lung GAP-associated protein GAP D	The outer lipoprotein of born of the same parents	AKA; PSPD; The mannose-binding protein relevant with the surfactant of lung
				SLC2A2	Solute carrier family 2 (easily GLUT), the member 2	GLUT	Uniqueness is expressed in the GLUT in b-cell and the liver. Transport glucose to the b-cell. Usually in NIDDM patient's islet cells, express low.
SLC2A4	Solute carrier family 2 (easily GLUT), the member 4	GLUT	Glucose transmits albumen, is the whole medium (rate-limiting step of glucose uptake) in the glucose uptake of insulin stimulating. Low expression is inessential, but the mistake in muscle and adipose tissue expresses one to demonstrating the transmission that has increased glucose.
				SMAC	The secondary wire plastochondria source activator of caspase	The mitochondria peptide	Promote the activation of caspase in cytochromes c/APAF-1/caspase 9 apoptosis pathway.
SOD2	Superoxide dismutase	2, mitochondrial	Oxidoreducing enzyme					The enzyme of free atomic group in removing and the failure line plastochondria

Symbol	Title	Classification	Describe
				SRP19	Signal recognition particle 19kD		Be responsible for the assembling of signal recognition particle. SRP protein is oriented to endoplasmic reticulum.
STAT1	The signal transducer of transcription factor 1 and activator, 91kD	DBP	Be combined with IFN IR element (ISRE) and GAS element, institute needs especially for the conduction of interferon signal. STAT1 can be activated by IFN-α, IFN-γ, EGF, PDGF and IL6. Cross the BRCA1 controlling gene that is expressed in the breast cancer generation and comprise STAT1 and JAK1.
				STAT3	The signal transduction of transcription factor 3 and activator	Transcription factor	AKA APRF: the transcription factor of acute phase response gene, in to the reaction of some kinases and growth factor, activate rapidly, be combined with the IL6 response element
TACI	Tumor necrosis factor receptor super family member 13b	Cell factor-chemotactic factor (CF)-growth factor	T cell activation factor and calcium cyclophilin modulator
				TEK	EGFR-TK, endothelium	The transferase acceptor	AKA TIE2, VMCM, the acceptor of angiopoietin-1 can be regulated and control endothelial cell propagation and differentiation, relates to vascular morphology and occurs. The TEK defective is relevant with venous malformation.
TERT	Reverse transcriptase of telomere	Transcriptase	The rich G telomere primer of external identification strand and by utilizing the RNA template to add a plurality of telomere repeated fragments cause end to its 3-nucleoprotein
				TGFA	The α transforming growth factor	Transferase/signal transduction	Proinflammatory cytokine is the main media thing of immune response nuclear regulation and control, with TH1Reaction is relevant, has mediated the reaction that the host stimulates bacterium, regulating cell growth and differentiation. The negative regulation of insulin effect
TGFB1	β
		1 transforming growth factor	Cell factor-chemotactic factor (CF)-growth factor	Short inflammation and anti-inflammatory activity, anti-apoptosis, cell-cell signal conduction can suppress or stimulating cellular growth
TGFB3	β
		3 transforming growth factors	The conduction of cell signal	Transmit signal by transmembrane serine/threonine kinases. The increase that TGFB3 expresses can cause tumor growth.

Symbol	Title	Classification	Describe
				TGFBR2	TGF, beta receptor II	Memebrane protein	AKA:TGFR2, the memebrane protein that relates in the conduction of cell signal and the activation, ser/thr protease is in conjunction with DAXX.

Symbol	Title	Classification	Describe
				TIMP1	Metalloproteinases	1 organize inhibitor	Protease/protease inhibitors	Irreversible combination also suppresses such as metalloproteinases such as clostridiopetidase As
TLR2	Toll sample acceptor 2	The conduction of cell signal and activation	The signal conductive medium that peptide glycan and fat teichoic acid are induced
				TLR4	Toll sample acceptor 4	The conduction of cell signal and activation	The signal conductive medium that LPS induces
TLX3	The T chronic myeloid leukemia is with source capsule 3	Transcription factor	DBP homeodomain family member. Can be activated in the T-ALL Leukomogenesis.
				TNF	TNF	Cell factor/Tumor Necrosis Factor Receptors aglucon	The negative regulation of insulin effect. The excessive generation of the adipose tissue of obese individuals-increase IRS-1 phosphorylation also reduces the insulin receptor kinase activity.
TNFA	α type TNF	Cell factor/chemotactic factor (CF)/growth factor	Short scorching, TH1Cell factor, Growth of Cells and differentiation are regulated in the reaction that the mediation host stimulates bacterium
				TNFRSF1   1A	Tumor necrosis factor receptor super family member 11a, the activator of NFKB	Acceptor	Activate NFKB1, important adjusting of T cell and dendritic cells interaction
TNFRSF1
	2	Tumor necrosis factor receptor super family member 12 (changing the position of the relevant memebrane protein of chain)	Acceptor	Induce to transfer and die and activates NF-к B, contain the deadly domain of a kytoplasm and membrane spaning domain

Symbol	Title	Classification	Describe
				TNFSF13   B	TNF (part) superfamily member 13b	Cell factor-chemotactic factor (CF)-growth factor	B cell activation factor, TNF family

Symbol	Title	Classification	Describe
				TNFSF5	TNF (part) superfamily member 5	Cell factor-chemotactic factor (CF)-growth factor	The part of CD40 is expressed in the T cell surface. It is by being incorporated into CD40 B cell surface regulation and control B cell function.
TNFSF6	TNF (part) superfamily member 6	Cell factor-chemotactic factor (CF)-growth factor	AKA FasL; FAS antigen part is converted into cell with the accent signal of dying
				TOSO	Fas-induces and transfers the conditioning agent of dying	Acceptor	Fas induces effective inhibitor that accent is died, TOSO expresses, similar FAS and FASL, after the activation of T cell, increase, old and feeble and be easy to transfer and die subsequently, express anti-the resisting-FAS-of hematopoietic cell of TOSO, the accent that FADD-and TNF-induce is died but the expression of increase transferring die inhibitor BCL2 and BCLXL, expresses TOSO and is reduced CASP8 and increase CFLAR by the cell that FAS activates and express, and this has suppressed CASP8 processing
TP53	Oncoprotein 53	DBP-cell cycle-tumour inhibitor	AKA P53: activate to suppress the gene expression of tumor growth and/or invasion, relate to the cell cycle regulation and control (the G1 phase grow stop required), stop and the accent inhibition Growth of Cells of dying by the active cell cycle

Symbol	Title	Classification	Describe
				TRADD	Domain and TNFRSF1A-interrelate by causing death	Co-receptor	Cross expressing of TRADD cause 2 main TNF induced reactions, transfer and die and the activation of NF-к B
TRAF1	TNF acceptor correlation factor 1	Co-receptor	Interact with TNFR2 cytoplasmic structure territory
				TRAF2	TNF acceptor correlation factor 2	Co-receptor	Interact with TNFR2 cytoplasmic structure territory

Symbol	Title	Classification	Describe
				TREM1	Triggering is expressed in the acceptor of bone marrow cell 1	The conduction of cell signal and activation	The 1g superfamily member is expressed in the acceptor on the bone marrow cell specially. TREM1 mediates neutrophil cell and monocytic activation and may have outstanding effect in inflammatory reaction.
UCP2	UCPS	2	The healthy indication of liver					From the synthetic uncoupling oxidative phosphorylation of ATP, with diabetes, fat relevant
				UGT	The UDP-glucuronyl transferase	The metabolism enzyme	Catalysis glucosiduronic acid and metabolism substrate, for all members of UGT1 family without right the engaging of Auele Specific Primer-probe
VCAM1	Vascular cell adhesion molecule 1	Cell adherence/stroma protein	AKA L1CAM; CD106; INCAM-100; Be specific to the cell surface adhesion molecule of blood leucocyte and some tumour cell, the mediation signal transduction may be relevant with arteriosclerotic progress and rheumatoid arthritis.
				VDAC1	Voltage dependent form anion channel 1	Memebrane protein	As the valtage-gated hole of mitochondrial outer membrane, thereby having accelerated opening of VDAC, front apoptotic proteins BAX and BAK allow cytochromes c to enter, anti-apoptotic proteins BCL2L1 is then by direct in conjunction with having closed VDAC with it.
VEGF	VEGF	Cell factor-chemotactic factor (CF)-growth factor	VPF: bring out vascular permeability, endothelial cell propagation and Angiogenesis. Produced by monocyte.

Symbol	Title	Classification	Describe
				VWF	The hereditary pseudohemophilia factor	Clotting factor	Be active in poly plasma glycoprotein in the blood clotting system as antihemophilic factor (VIIIC) carrier and blood platelet vascular wall medium. Secreted by endothelial cell.
XRCC5	In Chinese hamster cell 5, finish the X-ray reparative factor that defective is repaired	Unwindase	In the DNA plerosis double-strand break, play a role with dna ligase IV-XRCC4 compound.

Claims (261)

1. one kind based on the sample from the experimenter, measures the method for the experimenter's who suffers from infectious disease or the relevant inflammation of infectious disease spectrum data group, and described sample provides the RNA source, and the method comprises:

Utilize the amplification measurement corresponding to the amount of the RNA of at least 2 components in the table 1, and

Acquisition is to the measurement of each component,

Wherein said spectrum data group comprises measured value and the wherein said amplification of each component and is basically repeatably carrying out under the measuring condition.

2. according to the process of claim 1 wherein that described experimenter has the doubtful symptom that comprises the general infection of at least one in the following: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

3. according to the process of claim 1 wherein that the relevant inflammation of described infectious disease is the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

4. according to the method that be used for to measure the spectrum data group of claim 1, wherein said basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

5. according to the method that be used for to measure the spectrum data group of claim 1, wherein said basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

6. according to the method that is used for measuring the spectrum data group of claim 1, wherein basically similar for the amplification efficient of all components.

7. according to the method that be used for to measure the spectrum data group of claim 6, wherein for the amplification efficient of all components in 2%.

8. according to the method that be used for to measure the spectrum data group of claim 6, wherein for the amplification efficient of all components less than 1%.

9. according to any one method among the claim 1-8, wherein said sample is selected from blood, blood fraction, body fluid, a group cell or tissue from the experimenter.

10. method that characterizes infectious disease among the experimenter or the relevant inflammation of infectious disease, the method take from experimenter's sample as the basis, this sample provides the source of RNA, the method comprises:

Assess several members' spectrum data group, each member is the quantitative assay value of the amount of distinct rna component in one group of selected component, thereby can characterize the doubtful symptom of general infection by the measurement of described component, wherein said each component measured value is repeatably obtaining under the measuring condition basically.

11. according to the method for claim 10, wherein said experimenter has the doubtful symptom that comprises the general infection of at least one in the following: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

12. according to the method for claim 10, the doubtful symptom of the general infection that wherein said experimenter has is relevant with the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

13. according to the method that is used for characterizing experimenter's infectious disease and the relevant inflammation of infectious disease of claim 10, wherein said assessment further comprises:

Comparative map data group and for the baseline spectrum data group of this group, wherein said baseline spectrum data group are with infectious disease to be characterized or the relevant inflammation-related of infectious disease.

14. according to the method that is used for characterizing experimenter's infectious disease and the relevant inflammation of infectious disease of claim 10, wherein the amplification efficient of all components is basic simlarity.

15. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

16. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

17. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

18. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

19. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

21. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

21. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

22. according to the method for claim 10, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease comes the microorganism of free any classification to cause.

23. according to the method for claim 10, the relevant inflammation of wherein said infectious disease or infectious disease is relevant with experimenter's local organization, and described sample is from the fluid tissue that is different from this local organization type.

26. according to any one method among the claim 1-9, further comprise:

Storage spectrum data group is in digital storage media.

27. according to the method for claim 26, wherein store the spectrum data group and comprise it is stored in the database as record.

28. one kind based on first sample from the experimenter, the method for the relevant inflammation of infectious disease or infectious disease among the assessment experimenter, and described sample provides the RNA source, and the method comprises:

From first sample, derive first spectrum data group, this spectrum data group comprises a plurality of members, each member is the quantitative assay value of the amount of distinct rna component in one group of selected component, thereby can assess infectious disease or the relevant inflammation of infectious disease by the measurement of described component, wherein said each component measured value is repeatably obtaining under the measuring condition basically; And

Generation is for the spectrum data group of the calibration of this group, wherein each member of the spectrum data group of this calibration is the corresponding member's of baseline spectrum data group of the corresponding member of first spectrum data group and this group function, wherein said baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed

The spectrum data group of calibrating is to compare between first spectrum data group and baseline spectrum data group, thereby the assessment to experimenter's infectious disease or the relevant inflammation of infectious disease is provided.

29. according to the method for claim 28, wherein said experimenter has the doubtful symptom that comprises the general infection of at least one in the following: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

30. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease and the inflammation-related that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections or pneumonia or dentistry or gynemetrics check or treatment.

31. according to the method for claim 28, wherein said baseline spectrum data group is from one or more other samples that are different from the same experimenter who gathers in first sample sampling situation.

32. according to the method for claim 31, wherein said situation is selected from the time of (i) first sample collection, (ii) site of first sample collection, (ii) experimenter's biology situation during first sample collection.

33. according to the method for claim 31, wherein said one or more other samples are that one month time of interval gathers at least between first sample and described one or more other sample.

34. according to the method for claim 31, wherein said one or more other samples are that 12 months time of interval gathers at least between first sample and described one or more other sample.

35. according to the method for claim 31, wherein said one or more other samples gather before treatment is intervened.

36. according to the method for claim 31, wherein said one or more other samples gather after treatment is intervened.

37. according to the method for claim 28, wherein said first sample comes autoblood and baseline spectrum data group is come tissue or the body fluid of the experimenter beyond the autoblood.

38. according to the method for claim 28, wherein said first sample is from experimenter's tissue or body fluid, and baseline spectrum data group is come autoblood.

39. the method according to claim 31, wherein said baseline spectrum data group is from one or more other samples of same experimenter, the experimenter is under the biology state of the situation when being different from first sample collection during sampling, and this is at least with regard to following a kind of factor: age, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

40. according to the method for claim 28, wherein said baseline spectrum data group is derived since one or more different experimenters and next one or more other samples.

41. according to the method for claim 40, wherein said one or more different experimenters have one of following at least common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

42. the method according to claim 41, wherein said clinical indication for assessment of one or more different experimenters' infectious disease or the relevant inflammation of infectious disease, further comprises: explain the spectrum data group of calibrating under the background of other clinical indication at least one.

43. according to the method for claim 42, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radiation or metabolic imaging technology, other chemical assay and physical examination.

44. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

45. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

46. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

47. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

48. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

49. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

50. according to the method for claim 28, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

51. according to the method for claim 28, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease causes from the microorganism of any classification.

52. according to the method for claim 28, wherein said function is mathematical function and is different from simple difference.

53. according to the method for claim 52, wherein said function is the quadratic function of the corresponding member of first spectrum data group and the corresponding member's of baseline spectrum data group ratio.

54. according to the method for claim 53, wherein said function is logarithmic function.

55. according to the method for claim 53, if its numerical value difference of each member of spectrum data group that its alignment is crossed surpasses quantity D, think that then they have the biology conspicuousness, D=F (1.1)-F (.9) wherein, and F is quadratic function.

56. the method according to claim 28, wherein quantitatively finishing in first site of the acquisition of first sample and first spectrum data group comprises that utilizing network to enter in second site is stored in the database of digital storage media and produce the spectrum data group of calibrating.

57. according to the method for claim 56, further comprise and upgrade database to reflect from first quantitative spectrum data group of sample.

58. according to the method for claim 56, wherein the utilization of network comprises and enters the www worldwide web network.

59. according to the method for claim 28, wherein said quantified measures determines by amplification, and measuring condition is to make the amplification efficient of all components differ condition less than about 2%.

60. according to the method for claim 28, wherein said quantified measures determines by amplification, and measuring condition is to make the amplification efficient of all components differ condition less than about 1%.

61. one kind provides the method for the index of the relevant inflammation of indication experimenter's infectious disease or infectious disease based on first sample from the experimenter, described the first sample provides the RNA source, and the method comprises:

Obtain first spectrum data group from first sample, this spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby the measured value that makes this component becomes the indication of the doubtful symptom of general infection, described group comprises at least two components in the table 1 gene expression group, and when obtaining the spectrum data group

At the described measured value that basically repeatably obtains under the condition for each component, and

At least one measured value of spectrum data group is used in reference to scalar functions since then in the future, this target function provides the mapping of at least one measured value of spectrum data group to a measured value of the doubtful symptom of general infection, thereby produces relevant experimenter's infectious disease or the index of the relevant inflammation of infectious disease.

62. according to the method for claim 61, wherein said experimenter has the doubtful symptom that comprises following at least one general infection: with respect to the medical science standard, lencocyte count increase, temperature rising, heart rate quickening and blood pressure raise or reduce.

63. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease relates to the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

64. according to the method for claim 61, wherein said target function has 2 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

65. according to the method for claim 61, wherein said target function has 3 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

66. according to the method for claim 61, wherein said target function has 4 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

67. according to the method for claim 61, wherein said target function has 5 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

68. one kind provides the method according to the index of any one among the claim 61-67, wherein target function is set as every linear summation of following form:

$I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)},$

Wherein I is index, M_iThe value of spectrum data group membership i, C_iBe constant, P (i) is M_iThe power that improves, all integer value i of number of members ask summation in the data group to reaching.

69. one kind provides the method according to the index of claim 68, wherein said numerical value C_iAnd P (i) determines with statistical method, such as potential establishment mould etc., so that comprise that data and other any related data clinical, the experiment source are relevant with the doubtful symptom of general infection.

70. according to the method for claim 68, further be included as the standardized value that described index provides target function, it organizes mensuration with respect to relevant experimenter, thereby can explain this index with respect to standardized value.

71. according to the method for claim 70, thereby the wherein said standardized value that provides comprises that the structure target function makes standardized value approximate 1.

70. according to the method for claim 71, thereby wherein saidly provide standardized value to comprise to make up target function to make that the deviation for 0 represents with standard deviation units in standardized value approximate 0 and the target function.

72. according to the method for claim 71, wherein said relevant experimenter's group has one of following at least common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

73. according to the method for claim 72, wherein said relevant experimenter's group has one of following at least common trait: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

74. the method according to claim 68, for assessment of infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group, the method further comprises wherein said clinical indication: explain the spectrum data group of calibrating under the background of other clinical indication at least one.

75. according to the method for claim 74, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radioactivity or metabolic imaging technology, other chemical assay and physical examination.

76. according to the method for claim 61, wherein said quantified measures determines by amplification, and measuring condition is to make the amplification efficient of all components differ condition less than about 2%.

77. according to the method for claim 61, wherein said quantified measures determines by amplification, and measuring condition is to make the amplification efficient of all components differ condition less than about 1%.

78. according to the method that is used for providing index of claim 61, wherein basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

79. according to the method that be used for to measure the spectrum data group of claim 61, wherein basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

80. according to the method for claim 61, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

81. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

82. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

83. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

84. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

85. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

86. according to the method for claim 61, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

87. the method according to claim 61 further comprises:

From at least one other sample, obtain at least one other spectrum data group, described at least one other spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby the measured value that makes this component becomes the indication of the doubtful symptom of general infection

Wherein said at least one other sample is from same experimenter, sampling condition is different from the sampling condition of first sample, described condition is following at least a condition: time, nutrition history, medical situation, clinical indication, medicine processing, body movement, body weight and environmental exposure situation, and

To be used in reference in the scalar functions from least one measured value of described at least one other spectrum data group, this target function provides the mapping of at least one measured value of described at least one other spectrum data group to the measured value of infectious disease under the different condition or the relevant inflammation of infectious disease, thereby is created in the infectious disease of relevant experimenter under the condition that is different from first sample sampling condition or at least one other index of the relevant inflammation of infectious disease.

88. according to the method for claim 87, wherein said relevant experimenter's group has one of following common trait at least: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

89. according to the method for claim 88, wherein said relevant experimenter's group has one of following common trait at least: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health. 90. according to the method for claim 87, wherein said target function has 2 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

91. according to the method for claim 87, wherein said target function has 3 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

92. according to the method for claim 87, wherein said target function has 4 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

93. according to the method for claim 87, wherein said target function has 5 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

94. one kind provides the method according to the index of any one among the claim 87-93, wherein target function is set as every linear summation of following form:

$I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)},$

Wherein I is index, M_iThe value of spectrum data group membership i, C_iBe constant, P (i) is M_iThe power that improves is asked summation to all integer value i number of members to the data group.

95. one kind provides the method according to the index of claim 94, wherein said numerical value C_iAnd P (i) determines with statistical method, such as potential establishment mould etc., so that comprise that data and other any relevant data clinical, the experiment source are relevant with the doubtful symptom of general infection.

96. according to the method for claim 87, further be included as the standardized value that described at least one other index provides target function, it organizes mensuration with respect to relevant experimenter, thereby can explain described at least one other index with regard to standardized value.

97. according to the method for claim 96, thereby the wherein said standardized value that provides comprises that the structure target function makes standardized value approximate 1.

98. according to the method for claim 97, thereby wherein saidly provide standardized value to comprise to make up target function to make that the deviation for 0 represents with standard deviation units in standardized value approximate 0 and the target function.

99. according to the method for claim 94, wherein said clinical indication has been used to assess infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group, further comprises the spectrum data group after explaining calibration under the background of at least a other clinical indication.

100. according to the method for claim 139, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radioactivity or metabolic imaging technology, other chemical assay and physical examination.

101. according to the method for claim 87, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 2%.

102. according to the method for claim 87, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 1%.

103. according to the method that is used for providing index of claim 87, wherein basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

104. according to the method that be used for to measure the spectrum data group of claim 87, wherein basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

105. according to the method for claim 87, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

106. according to the method for claim 87, the relevant inflammation of wherein said infectious disease or infectious disease comprises at least two kinds of components of table 1 from the group of microorganism infection and component.

107. according to the method for claim 87, the relevant inflammation of wherein said infectious disease or infectious disease comprises at least two kinds of components of table 1 from the group of bacterium infection and component.

108. according to the method for claim 87, the relevant inflammation of wherein said infectious disease or infectious disease comprises at least two kinds of components of table 1 from the group of eucaryon parasitic infection and component.

109. according to the method for claim 87, the relevant inflammation of wherein said infectious disease or infectious disease comprises at least two kinds of components of table 1 from the group of virus infections and component.

110. according to the method for claim 87, the relevant inflammation of wherein said infectious disease or infectious disease comprises at least two kinds of components of Table X from the group of fungal infection and component.

111. according to the method for claim 87, the group that the relevant inflammation of wherein said infectious disease or infectious disease is systemic inflammatory response syndrome (SIRS) and component comprises at least two kinds of components of Table X. The doubtful symptom of general infection.

112. one kind based on from first sample assessment experimenter's infectious disease of experimenter or the method for the relevant inflammation of infectious disease, described first sample provides the RNA source, and the method comprises:

Obtain first spectrum data group from first sample, this spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby can assess infectious disease or the relevant inflammation of infectious disease from the measured value of this component, wherein the described measured value of each component is repeatably obtaining under the measuring condition basically, and

Generation is for the spectrum data group of the calibration of this group, wherein each member of the spectrum data group of this calibration is the corresponding member's of baseline spectrum data group of the corresponding member of first spectrum data group and this group function, wherein said each member of baseline spectrum data group is the standardization measured value for the amount of component in the group of relevant experimenter's mensuration, and described baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed

The spectrum data group of calibrating is to compare between first spectrum data group and baseline spectrum data group, thereby the assessment to experimenter's infectious disease or the relevant inflammation of infectious disease is provided.

113. according to the method for claim 112, wherein said experimenter has the doubtful symptom that comprises at least with the general infection of the next item down: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

114. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease relates to the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

113. according to the method for claim 112, wherein said relevant experimenter's group is one group of health volunteer.

114. according to the method for claim 112, wherein said relevant experimenter's group has one of following common trait at least: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

115. the method according to claim 114, for assessment of infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group, the method further comprises wherein said clinical indication: explain the spectrum data group of calibrating under the background of other clinical indication at least one.

116. according to the method for claim 115, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radioactivity or metabolic imaging technology, other chemical assay and physical examination.

117. according to the method for claim 112, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 2%.

118. according to the method for claim 112, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 1%.

119. according to the method for claim 112, wherein basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

120. according to the method for claim 112, wherein basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

121. according to the method for claim 112, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

122. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

123. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

124. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

125. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

126. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

127. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

128. according to the method for claim 112, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

129. according to the method for claim 112, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease causes from the microorganism of any classification.

130. the method according to claim 112 further comprises:

The spectrum data group is stored in the digital storage media.

131. according to the method for claim 130, wherein store the spectrum data group and comprise it is stored in the database as record.

132. according to the method for claim 112, wherein said baseline spectrum data group is come comfortable one or more other samples that are different from the same experimenter who gathers under first sample sampling condition.

133. according to the method for claim 132, wherein said one or more samples gather before treatment is intervened.

134. according to the method for claim 132, wherein said one or more samples gather after treatment is intervened.

135. according to the method for claim 132, wherein said one or more samples are to gather in initial sample and the time in this at least 1 month sample collection time interval.

136. according to the method for claim 132, wherein said one or more samples are to gather in initial sample and the time in this at least 12 months sample collection time intervals.

137. according to the method for claim 112, wherein said first sample comes autoblood and baseline spectrum data group is come tissue or the body fluid outside the autoblood.

138. according to the method for claim 112, wherein said first sample is from experimenter's tissue or body fluid and baseline spectrum data group is come autoblood.

139. one kind based on from first sample of experimenter with from second sample assessment experimenter's of the indicator cells group who determines infectious disease or the method for the relevant inflammation of infectious disease, described sample provides the source of RNA, described method comprises:

First sample or its part are added on definite indicator cells group;

Obtain first spectrum data group from second sample, this spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna or protein component in one group of selected component, thereby can detect the doubtful symptom of general infection from the measured value of this component, wherein the described measured value of each component is repeatably obtaining under the measuring condition basically, and

Generation is for the spectrum data group of the calibration of this group, wherein each member of the spectrum data group of this calibration is the corresponding member's of baseline spectrum data group of the corresponding member of first spectrum data group and this group function, wherein said each member of baseline spectrum data group is the amount of one of component in the group of mensuration of standardization measured value organize to(for) relevant experimenter, and described baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed

The spectrum data group of calibrating is to compare between first spectrum data group and baseline spectrum data group, thereby the assessment to experimenter's infectious disease or the relevant inflammation of infectious disease is provided.

140. according to the method for claim 139, wherein said experimenter has the doubtful symptom that comprises at least with the general infection of the next item down: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

141. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease relates to the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

142. according to the method for claim 139, wherein said relevant experimenter's group is one group of health volunteer.

143. according to the method for claim 139, wherein said corresponding experimenter has one of following common trait at least: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

144. the method according to claim 143, for assessment of infectious disease or the relevant inflammation of infectious disease of relevant experimenter's group, the method further comprises wherein said clinical indication: explain the spectrum data group of calibrating under the background of other clinical indication at least one.

145. according to the method for claim 144, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radioactivity or metabolic imaging technology, other chemical assay and physical examination.

146. according to the method for claim 139, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 2%.

147. according to the method for claim 139, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 1%.

148. according to the method for claim 139, wherein basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

149. according to the method for claim 139, wherein basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

150. according to the method for claim 139, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

151. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

152. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

153. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

154. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

155. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

156. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

157. according to the method for claim 139, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

158. according to the method for claim 139, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease causes from the microorganism of any classification.

159. the method according to claim 139 further comprises:

Storage spectrum data group is in digital storage media.

160. according to the method for claim 139, wherein store the spectrum data group and comprise it is stored in the database as record.

161. according to the method for claim 139, wherein said baseline spectrum data group is come comfortable one or more other samples that are different from the same experimenter who gathers under first sample sampling condition.

162. according to the method for claim 161, wherein said one or more samples gather before treatment is intervened.

163. according to the method for claim 161, wherein said one or more samples gather after treatment is intervened.

164. according to the method for claim 161, wherein said one or more samples are to gather in initial sample and the time in this at least 1 month sample collection time interval.

165. according to the method for claim 161, wherein said one or more samples are to gather in initial sample and the time in this at least 12 months sample collection time intervals.

166. according to the method for claim 139, wherein said first sample comes autoblood and baseline spectrum data group is come tissue or the body fluid outside the autoblood.

167. according to the method for claim 139, wherein said first sample is from experimenter's tissue or body fluid and baseline spectrum data group is come autoblood.

168. an assessment is subjected to the target cell group's that the first reagent affects infectious disease or the method for the relevant inflammation of infectious disease, the sample of oneself having used the target cell group of the first reagent since it is the basis, and this sample provides the source of RNA, and described method comprises:

Obtain first spectrum data group from described sample, this first spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby can assess infectious disease or the relevant inflammation of infectious disease that affected by the first reagent from the measured value of this component, wherein the described measured value of each component is repeatably obtaining under the measuring condition basically, and

Generation is for the spectrum data group of the calibration of this group, wherein each member of the spectrum data group of this calibration is the corresponding member's of baseline spectrum data group of the corresponding member of first spectrum data group and this group function, wherein said each member of baseline spectrum data group is the standardization measured value with respect to the amount of one of component in the group of target cell faciation pass group mensuration, and wherein said baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed

The spectrum data group of calibrating is to compare between first spectrum data group and baseline spectrum data group, thereby provides the infectious disease that is subjected to the target cell group that the first reagent affects or the assessment of the relevant inflammation of infectious disease.

169. according to the method for claim 168, wherein said target cell group has the doubtful symptom that comprises at least with the general infection of the next item down: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

170. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease relates to the inflammation that is caused by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

171. according to the method for claim 168, the target cell group that wherein said relevant group of target cell group is one group of health.

172. according to the method for claim 168, wherein said relevant group of target cell group has one of following common trait at least: age, sex, race, geographical position, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health.

173. the method according to claim 172, for assessment of reference group target cell group's infectious disease or the relevant inflammation of infectious disease, the method further comprises wherein said clinical indication: explain the spectrum data group of calibrating under the background of other clinical indication at least one.

174. according to the method for claim 173, wherein said at least one other clinical indication is selected from: blood chemistry, urinalysis, X-ray or other radioactivity or metabolic imaging technology, other chemical assay and physical examination.

175. according to the method for claim 168, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 2%.

176. according to the method for claim 168, wherein said quantified measures is determined by amplification, and measuring condition is that the amplification efficient of all components is differed less than about 1%.

177. according to the method for claim 168, wherein basically repeatably measuring condition be to be better than 5 percentage points degree with interior in repeatability.

178. according to the method for claim 168, wherein basically repeatably measuring condition be to be better than 3 percentage points degree with interior in repeatability.

179. according to the method for claim 168, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

180. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

181. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

182. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

183. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

184. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

185. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

186. according to the method for claim 168, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

187. according to the method for claim 168, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease causes from the microorganism of any classification.

188. the method according to claim 168 further comprises:

Storage spectrum data group is in digital storage media.

189. according to the method for claim 188, wherein store the spectrum data group and comprise it is stored in the database as record.

190. according to the method for claim 168, wherein said first sample come autoblood and baseline spectrum data group from the experimenter tissue that is different from blood or body fluid.

191. according to the method for claim 168, wherein said first sample is from experimenter's tissue or body fluid and baseline spectrum data group is come autoblood.

192. according to the method for claim 168, wherein said baseline spectrum data group is come comfortable one or more other samples that gather in first sample collection situation from same experimenter that are different from.

193. according to the method for claim 192, wherein said one or more other samples gather before treatment is intervened.

194. according to the method for claim 192, wherein said one or more other samples gather after treatment is intervened.

195. according to the method for claim 192, wherein said one or more other samples are to gather in initial sample and the time in this at least 1 month sample collection time interval.

196. one kind with respect to the target cell group infectious disease that affected by the second reagent or the relevant inflammation of infectious disease, assessment is subjected to the target cell group's that the first reagent affects infectious disease or the method for the relevant inflammation of infectious disease, since oneself used the first reagent the target cell group first sample and come oneself to use the second reagent the target cell group second sample for the basis, described sample provides the RNA source, and described method comprises:

Obtain first spectrum data group and from second sample, obtain second spectrum data group from described first sample, this first and second spectrum data group comprise separately a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby can assess with the second reagent from the measured value of this component and to compare, the infectious disease or the relevant inflammation of infectious disease that affected by the first reagent, wherein the described measured value of each component is repeatably obtaining under the measuring condition basically, and

The spectrum data group that generation was calibrated for first spectrum data group of calibrating and second of this group, wherein each member of (i) first spectrum data group of calibrating is the corresponding member's of baseline spectrum data group of the corresponding member of first spectrum data group and this group function, and (ii) each member of second spectrum data group of calibrating is the corresponding member's of baseline spectrum data group of the corresponding member of second spectrum data group and this group function, wherein said each member of baseline spectrum data group is the standardization measured value for the amount of one of component in the group of relevant group experimenter mensuration, and wherein said baseline spectrum data group and infectious disease or the relevant inflammation-related of infectious disease to be assessed

First and second spectrum data group of calibrating are comparison between first spectrum data group and the baseline spectrum data group and the comparison between second spectrum data group and the baseline spectrum data group, thereby provide with respect to the target cell group's who affected by the second reagent infectious disease or the relevant inflammation of infectious disease, on the infectious disease that is subjected to the target cell group that the first reagent affects or the assessment of the relevant inflammation of infectious disease.

197. according to the method for claim 196, wherein said target cell group has the doubtful symptom that comprises at least with the general infection of the next item down: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

198. according to the method for claim 196, wherein said target cell group has and relates to the doubtful symptom of general infection that is caused inflammation by following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

199. according to the method for claim 196, wherein said the first reagent is the first medicine, and the second reagent is the second medicine.

200. according to the method for claim 196, wherein said the first reagent is a kind of medicine, and the second reagent is a kind of complex mixture.

201. according to the method for claim 196, wherein said the first reagent is a kind of medicine, and the second reagent is a kind of nutrient drug.

202. according to the method for claim 196, wherein said quantified measures is measured by amplification, and measuring condition to be the amplification efficient of all components differ less than about 2%.

203. according to the method for claim 196, wherein said quantified measures is measured by amplification, and measuring condition to be the amplification efficient of all components differ less than about 1%.

204. according to the method for claim 196, wherein basically repeatably measuring condition be within repeatability is better than 5% degree.

205. according to the method for claim 196, wherein basically repeatably measuring condition be within repeatability is better than 3% degree.

206. according to the method for claim 196, wherein the relevant inflammation of evaluated infectious disease or infectious disease is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

207. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

208. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

209. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

210. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

211. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

212. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

213. according to the method for claim 196, the relevant inflammation of wherein said infectious disease or infectious disease is from bacteremia, viremia virusemia or fungemia.

214. according to the method for claim 196, the septicaemia that the relevant inflammation of wherein said infectious disease or infectious disease causes from the microorganism of any classification.

215. the method according to claim 196 further comprises:

Storage spectrum data group is in digital storage media.

216. according to the method for claim 196, wherein store the spectrum data group and comprise it is stored in the database as record.

217. according to the method for claim 196, wherein said baseline spectrum data group is come comfortable one or more other samples that gather under first sample sampling condition from same experimenter that are different from.

218. according to the method for claim 196, wherein said baseline spectrum data group is come comfortable one or more other samples that gather under second sample sampling condition from same experimenter that are different from.

219. according to the method for claim 196, wherein said first sample come autoblood and baseline spectrum data group from the experimenter tissue that is different from blood or body fluid.

220. according to the method for claim 196, wherein said first sample is from experimenter's tissue or body fluid and baseline spectrum data group is come autoblood.

221. one kind provides the method for index of the experimenter's that indication has the doubtful symptom of general infection inflammation based on first sample from the experimenter, described the first sample provides the RNA source, and the method comprises:

Obtain a spectrum data group from first sample, this spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby the measured value that makes this component becomes the indication of inflammation, described group of at least two components that comprise table 1 gene expression group, and

When obtaining the spectrum data group,

At the described measured value that basically repeatably obtains under the condition for each component, and in the future since then at least one measured value of spectrum data group be used in reference to scalar functions, this target function provides the mapping of at least one measured value of spectrum data group at least one measured value of inflammation, thereby produces the index relevant with the sample inflammation;

Wherein said target function has used from the data for the baseline spectrum data group of this group, each member of baseline spectrum data group is the amount of one of component in the group of mensuration of standardization measured value organize to(for) relevant experimenter, wherein said baseline spectrum data group and inflammation-related to be assessed.

222. according to the method for claim 221, wherein said experimenter has the doubtful symptom that comprises at least with the general infection of the next item down: with respect to the medical science standard, lencocyte count increases, temperature raises, heart rate is accelerated and blood pressure raises or reduction.

223. according to the method for claim 221, the doubtful symptom of wherein said general infection relates to by the caused inflammation of following at least a factor: blunt wound or penetrating trauma, operation, endocarditis, urinary tract infections, pneumonia or dentistry or gynemetrics check or treatment.

224. according to the method for claim 221, wherein said target function has 2 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

225. according to the method for claim 221, wherein said target function has 3 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

226. according to the method for claim 221, wherein said target function has 4 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

227. according to the method for claim 221, wherein said target function has 5 kinds of compositions that comprise morbid state, being in a bad way property or disease process.

228. one kind provides the method according to the index of any one among the claim 221-227, wherein target function is set as every linear summation of following form:

$I=\mathrm{\Σ}{C}_i{M}_i^{P\left(i\right)},$

Wherein I is index, M_iThe value of spectrum data group membership i, C_iBe constant, P (i) is M_iThe power that improves is asked summation to all integer value i number of members to the data group.

229. one kind provides the method according to the index of claim 228, wherein said numerical value C_iAnd P (i) determines with statistical method, such as potential establishment mould etc., so that comprise that data and other any related data clinical, the experiment source are relevant with the doubtful symptom of general infection.

230. according to the method for claim 221, further be included as the standardized value that described at least one other index provides target function, measure with regard to relevant experimenter's group, thereby can explain described index by just relevant standardized value.

231. according to the method for claim 221, wherein said quantified measures is measured by amplification, and measuring condition to be the amplification efficient of all components differ less than about 2%.

232. according to the method for claim 221, wherein said quantified measures is measured by amplification, and measuring condition to be the amplification efficient of all components differ less than about 1%.

234. according to the method for claim 221, wherein basically repeatably measuring condition be within repeatability is better than 5% degree.

235. according to the method for claim 221, wherein basically repeatably measuring condition be within repeatability is better than 3% degree.

236. according to the method for claim 221, wherein evaluated inflammation is with regard to experimenter's local organization, first sample is then from the tissue that is different from this local organization type or fluid.

237. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease infects from microorganism.

238. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease infects from bacterium.

239. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease is from eucaryon parasitic infection.

240. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease is from virus infections.

241. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease is from fungal infection.

242. according to the method for claim 221, the relevant inflammation of wherein said infectious disease or infectious disease is from systemic inflammatory response syndrome (SIRS).

243. one kind provides the method according to the indication of claim 221, further comprises:

Obtain at least one other spectrum data group from least one other sample, described at least one other spectrum data group comprises a plurality of members, each member is the quantified measures of the amount of distinct rna component in one group of selected component, thereby makes the measured value of this component become the indication of inflammation

Wherein said at least one other sample is what to gather from same experimenter in the situation that is different from first sample sampling condition with regard to following at least one factor: time, nutrition history, medical situation, clinical indication, medicine are processed, activity, body weight and the environmental exposure situation of health; And

To be used in reference in the scalar functions from least one measured value of described at least one other spectrum data group, this target function provides the mapping of at least one measured value of at least one other spectrum data group at least one measured value of inflammation under the different situations, is different from least one relevant with experimenter's inflammation under first sample sampling condition other index thereby be created in.

244. the method with index guiding treatment intervention in infectious disease or the relevant inflammation patient of infectious disease, described method comprises:

Provide according to any one index in the claim 61,87,221 or 243;

Described index and the standardized value of this index of relevant group of experimenter's mensuration just compared obtain difference;

Utilize the difference guiding treatment intervention between the standardized value of described index and this index.

245. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is the special therapy of microorganism.

246. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is the special therapy of bacterium.

247. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is the special therapy of fungi.

248. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is the special therapy of virus.

249. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is the special therapy of eucaryon parasite.

250. according to the method for utilizing the index guiding treatment to intervene of claim 244, wherein said treatment intervention is for host immune system.

251. distinguish the method for pathogen type in the pathogen of the classification in the relevant inflammation patient of infectious disease or infectious disease, the method take from least one sample of experimenter as the basis, described sample provides the source of RNA, described method comprises:

Mensuration is at least one spectrum data group according to claim 1 of experimenter;

More described spectrum data group obtains difference with at least one baseline spectrum data group with at least one relevant group of sample determination in the pathogen of a classification,

Will be for distinguishing in the class pathogen of the pathogen type at least one spectrum data group of this experimenter from least one baseline spectrum data group with this difference.

252. according to the method that is used for distinguishing in a class pathogen pathogen type of claim 251, wherein said Pathogen category is microorganism.

253. according to the method that is used for distinguishing in a class pathogen one type pathogen of claim 252, wherein said Pathogen category is bacterium.

254. according to the method that is used for distinguishing in a class pathogen pathogen type of claim 253, wherein said difference is used for distinguishing gram (+) bacterial pathogens from gram (-) bacterial pathogens.

255. according to the method that is used for distinguishing in a class pathogen pathogen type of claim 252, wherein said Pathogen category is fungi.

256. according to the method for distinguishing pathogen type from a class nosomycosis substance of claim 255, wherein said difference is used to distinguish acute Mycotoruloides pathogen from chronic Mycotoruloides pathogen.

257. according to the method that is used for distinguishing in a class pathogen pathogen type of claim 252, wherein said Pathogen category is viral.

258. according to the method for distinguishing pathogen type from a viroid disease substance of claim 257, wherein said difference is used to distinguish the dna virus pathogen from the RNA viral pathogen.

259. according to the method for distinguishing pathogen type from a viroid disease substance of claim 257, wherein said difference is used to distinguish the rhinovirus pathogen from the influenza pathogen.

260. according to the method for distinguishing pathogen type from a class pathogen of claim 252, wherein said Pathogen category is the eucaryon parasite.

261. according to the method for distinguishing pathogen type from a class eucaryon parasitic disease substance of claim 260, wherein said difference is used to distinguish plasmodium parasitic disease substance from the trypanosomiasis substance.

262. the method for pathogen type in the pathogen of in the patient of the relevant inflammation of infectious disease or infectious disease, distinguishing a classification with index, the method take from least one sample of experimenter as the basis, described method comprises:

Mensuration is according to any one at least one index for the experimenter in the claim 61,87,221 or 243;

The standardized value of more described at least one index and the mensuration of at least one index organize to(for) at least one relevant experimenter to be obtaining difference,

From the pathogen of described classification, distinguish pathogen type with at least one difference between at least one standardized value of described at least one index and this index thereof.

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