CN109475305A - Method and system for microbial medicine genomics - Google Patents
Method and system for microbial medicine genomics Download PDFInfo
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- CN109475305A CN109475305A CN201780043788.6A CN201780043788A CN109475305A CN 109475305 A CN109475305 A CN 109475305A CN 201780043788 A CN201780043788 A CN 201780043788A CN 109475305 A CN109475305 A CN 109475305A
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Abstract
The embodiment of the method and system of pharmacogenomics for microorganism may include: sample processing system, it can operate to collect the container containing the substance gathered from user, the processing system includes the sequencing system that can be operated to determine the microorganism sequence for carrying out biological sample；Microbial population characterizes system, it can operate to determine microbial population pharmacogenomics data based on microorganism sequence, the supplementary data associated with antibiotic associated disease gathered with the user is collected, and is converted to the characterization model with antibiotic associated disease by supplementary data and from the feature that microbial population pharmacogenomics data are extracted；And treatment system, user's biomaterial is characterized with antibiotic associated disease based on being directed to using characterization model, the treatment system can be operated to promote the treatment to the antibiotic associated disease of user.
Description
Cross reference to related applications
The application is that (it is in October, 2015 by the U.S. Patent application No.15/606,743 that submits on May 26th, 2017
The connecting of the U.S. Patent application for the Serial No. 14/919,614 submitted for 21st) continuation in part application, wherein Serial No.
14/919,614 U.S. Patent application requires the U.S. for the Serial No. 62/066,369 submitted on October 21st, 2014 to face
When application, submitted on December 04th, 2014 Serial No. 62/087,551 U.S. Provisional Application, December 17 in 2014
The U.S. Provisional Application for the Serial No. 62/092,999 that day submits, the sequence number 62/147 submitted on April 14th, 2015,
376 U.S. Provisional Application, the Serial No. 62/147,212 submitted on April 14th, 2015 U.S. Provisional Application, in
The U.S. Provisional Application for the Serial No. 62/147,362 that on April 14th, 2015 submits, in the sequence submitted on April 13rd, 2015
Number for 62/146,855 U.S. Provisional Application and the Serial No. 62/206,654 submitted for 18th in August in 2015 the U.S.
The equity of provisional application, these applications are incorporated herein by reference in their entirety respectively.
The application also requires the power of the U.S. Provisional Application for the Serial No. 62/361,943 submitted on July 13rd, 2016
Benefit is incorporated herein by reference in their entirety.
Technical field
Present invention relates in general to microbiological art, relate more specifically in microbiological art for characterizing and micro- life
The new and useful method and system of object pharmacogenomics.
Background technique
Microbial population is the ecological community of commensalism relevant to organism, symbiosis and pathogenic microorganisms.Human microbial
Group system includes and the human cell that is present in entire human body microbial cell as many, but due to sample treatment technology, lose
Pass the limitation in terms of analytical technology and resource for handling mass data, to the characterization of human microbial group system still in
Initial stage.Nevertheless, microbial population it is under a cloud many relevant to health/disease states (for example, prepare to give a birth,
Diabetes, autoimmune disorders, gastrointestinal disorders, rheumatoid obstacle, neurological disorder etc.) at least partly play effect.It examines
Consider micropopulation and tie up to the profound impact for influencing the health aspect of subject, should pay with the characterization of microbial population, by this
Characterization forms opinion and generates the relevant effort of therapy for being configured as restoring from ecological disturbance state.However, currently used for
Analysis human microbial group system and the method and system for providing remedy measures based on obtained opinion are still left many and are not yet solved
The problem of answering.Especially since the limitation of current techniques, based on microbial population composition characteristic and/or functional character come table
It levies the method for certain health status and the treatment that is adaptively adjusted for specific subject is (for example, probiotics/prebiotics
(prebiotic) treatment, fecal microorganism group's transplanting etc.) it is still infeasible.
Therefore, it in microbiological art, needs a kind of for being used for microorganism medicine in a manner of individuation and population-wide
The new and useful method and system of object genomics.The present invention provides such a new and useful method and it is
System.
Detailed description of the invention
Figure 1A -1B depicts the schematic flow of the embodiment variants of the method for microbial medicine genomics
Figure；
Fig. 2 depicts the embodiment variants of the system and method for microbial medicine genomics；
Fig. 3 depicts the change of the process for generating model in the embodiment of the method for microbial medicine genomics
Type；
Fig. 4 is depicted treats the defeated of model in the embodiment of the method and system for microbial medicine genomics
Modification out；
Fig. 5 depicts the modification of the application model in the embodiment of the method for microbial medicine genomics；
Fig. 6 depicts the change that multiple models are applied in the embodiment of the method for microbial medicine genomics
Type；
Fig. 7 depicts the change for promoting treatment in the modification of the embodiment of the method for microbial medicine genomics
Type；
Fig. 8 depicts the therapy based on probiotics and grasps in the embodiment of the method for microbial medicine genomics
The modification of the mechanism of work；
Fig. 9 depicts the modification of the notice in the embodiment of the method for microbial medicine genomics；
Figure 10 is depicted in the embodiment of the method for microbial medicine genomics for offer and antibiotic
The modification at the interface of relevant information；
Figure 11 depicts the modification of the notice in the embodiment of the method for microbial medicine genomics；
Figure 12 depicts the sample treatment parameter in the embodiment of the method for microbial medicine genomics and changes
The modification of change.
Specific embodiment
The description of embodiment of the present invention is had no intention below to limit the invention to these embodiments, and is intended to make this
Field technical staff is able to carry out and uses the present invention.
1, it summarizes
As shown in Fig. 2, for being directed to user (for example, human experimenter, patient, animal subjects, environmental ecology system
System, caregiver etc.) embodiment of characterization (for example, assessment) and the system 200 of antibiotic associated disease can wrap
Include one or more of the following terms: processing system 210 (for example, sample processing system) can be operated to collect and contain
There are the container of the substance (for example, biological sample etc. of microbial nucleic acids substance) from user's set, the processing system
System 210 includes the sequencing system (sequenator system) that can be operated to determine microorganism sequence by the way that substance is sequenced；
Microbial population characterizes system 220, can operate to determine microbial population pharmacogenomics number based on microorganism sequence
According to (and/or at least one of microbial population composition data and microbial population functional diversity data), collection makes with described
The antibiotic of user's set can treat the relevant supplementary data of illness, and by supplementary data and from microbial population drug
Genomics data (and/or at least one of microbial population composition data and microbial population functional diversity data) institute
The feature of extraction is converted to the characterization model with antibiotic associated disease；And/or treatment system (for example, medical treatment system) 230, base
In characterizing user's biomaterial with characterization model relevant to antibiotic associated disease, the treatment system can be operated to promote
Inserting needle to the treatment of the user of antibiotic associated disease (for example, medical treatment) (for example, treatment can operate it is micro- to adjust user
Biotic formation composition is to improve the state etc. of antibiotic associated disease).
System 200 and method 100 can be played according to micropopulation relevant to one or more antibiotic associated diseases
It is the effect of data set characterization and/or diagnosis user (as used for clinical diagnosis, with the characterization model of diagnosis).System
200 and method 100 can additionally or alternatively play promotion (offer) to the treatment (such as remedy measures) of user and/or
Implement proper function.Compared with current standard is based on antibiotic treatment, miscellaneous system 200 and/or method 100 can be with
For generating or providing personalized antibiotic regime in fast and efficient manner.Miscellaneous system 200 and/or method
100 can further be conducive to the therapy for being supplied to subject is monitored and/or adjusted (for example, by entirely controlling
The additional sample from subject is carried out during treatment point to examine (reception), processing and analysis).
System 200 and method 100 can preferably generate and promote to antibiotic associated disease (for example, antibiotic can be controlled
Treat illness) characterization and/or treatment, may include any one or more of in following item: symptom, the cause of disease, disease, imbalance,
Microbial population pharmacogenomics spectrum is (for example, description can treat the resistance and/or sensitivity of the antibiotic of illness for antibiotic
Property) and/or any other suitable aspect relevant to antibiotic associated disease.Antibiotic associated disease may include following Xiang Zhongren
What is one or more: stranguria syndrome, urinary tract infections, trichomoniasis, acne, ecphyaditis, atrial septal defect, ureterocele, urethra are comprehensive
Simulator sickness, urethritis, pulmonary tuberculosis, bacterial arthritis, bacterial vaginosis BV, dizziness, disequilibrium, pressure ulcer, bursal synovitis, branch
Tracheitis, syphilis, tonsillitis, pharyngitis, septicemia, pyelonephritis, ear infection, hearing disability, peritonitis, pericarditis, basin
Chamber inflammation, meningitis, laryngitis, Strep throat, sinus infection, other sexually transmitted diseases, other with skin-related conditions, other
The infection and/or any other suitable antibiotic phase that ear's associated disease, other oral area associated diseases, other bacteriums induce
Close illness.
One or more examples of method described herein 100 and/or process can by and/or using one or more
The example of a system described herein 200, component and/or entity not simultaneously (for example, sequentially), simultaneously (for example, parallel
Ground；Be performed simultaneously on different threads with improved for parallel computation sample treatment and/or for determining calculation processing and/
Or feature and/or treatment that illness relevant to antibiotic is provided etc.), with the time relationship of trigger event, and/or with any conjunction
Suitable time and frequency carry out.However, method 100 and/or system 200 can configure in any suitable manner.
2, benefit
Microbial population analysis may be implemented to caused by microorganism and/or otherwise it is relevant to microorganism with it is anti-
The accurate and Efficient Characterization of raw element associated disease and/or treatment supply.The technology can overcome conventional method to antibiotic phase
Several challenges closed the characterization of illness and/or treatment is promoted to be faced.Firstly, conventional method can require patient access one or
Multiple caregivers are directed to the characterization and/or treatment recommendations of antibiotic associated disease to receive, and this can be equivalent to and diagnose/
Or the relevant inefficient and health risk of time quantum passed before treatment.Secondly, the conventional base for human genome sequencing
Because sequencing and analytical technology be applied to microbial population when (for example, wherein human microbial group system may include thinner than the mankind
Microbial cell of the born of the same parents mostly more than 10 times；Wherein best sample processing technique can be different；Wherein sequence reference database can be with
It is different；Wherein microbial population characterization may include considering that the different microorganisms group across group and/or individual is Drug Discovery
Learn spectrum；Wherein the distinct methods of microbial population pharmacogenomic analysis and human genome pharmacogenomic analysis may
It is different；Wherein microbial population can change etc. between the different body regions of user) may be it is incompatible and/
Or it is inefficient.Again, sequencing technologies (for example, next-generation sequencing) if not appearance caused and carry out sequencing phase with to inhereditary material
The unprecedented development that the speed and data of pass generate will not be (for example, data processing problem, information
Display problem, microbial population problem analysis, treatment forecasting problem, treatment supply problem etc.).The reality of system 200 and method 100
The solution of technology origin can be provided at least the above challenge by applying example.
Firstly, the technology can be assigned by promoting the computer performance of previously not executable function to computer phase
Pass technology is (for example, personalized characterization and/or treatment-related modeling with determining antibiotic associated disease；Microbial population medicine
Object genomics calculates analysis；Calculation processing relevant to biological sample processing etc.) improvement.For example, based on the technology of deriving from
(for example, using microorganism reference sequence database, (such as genome refers to alliance (Genome Reference
Consortium microbial population pharmacogenetic group data))), the technology calculably generate microbial population characterization and
Recommend for therapy with antibiotic associated disease, the technology recently due to sample treatment technology and sequencing technologies development and
It is feasible.
Secondly, the technology can be assigned to processing speed, the accuracy of microbial population characterization, microbial population associated treatment
It determines and promotes, and/or the improvement of other suitable aspects related with antibiotic associated disease.The technology can be generated and apply
Feature selecting rule is (for example, microbial population pharmacogenomics feature selecting rule；Antibiotic correlated characteristic selection rule),
With from potentially large number of feature pool select (for example, can be extracted from a large amount of microbial population data) optimize character subset
(for example, microbial population composition characteristic, microbial population functional diversity feature etc.) for generate and apply characterization model with/
Or treatment model (for example, antibiotic treatment model).Microbial population is (for example, human microbial group system, animal microorganism group system
Deng) potential size can be converted to mass data, create the problem that how to handle and analyze mass data array to generate
Feasible microbial population opinion relevant to antibiotic associated disease.However, feature selecting rule and/or other suitable meters
The achievable rule of calculation machine may be implemented shorter generation and execute the time (for example, for generation and/or application decision tree mould
Type), model simplification be conducive to effective explanation to result, reduce overfitting, in data source (for example, for collecting and locating
Manage microbial population data set (such as microbial population pharmacogenomics data set, microbial population composition data collection, micro- life
Object group is functional diversity data set etc.)) improvement, identification and present relevant to microbial population antibiotic related diseases symptoms include
Solution is (for example, by collecting and handling prediction of the more and more data relevant to more and more users to develop skill
Ability) improvement, data storage and search is (for example, storage particular model relevant to user and/or user's set, micro-
Biological sequence, feature and/or other suitable data are to improve personalized characterization and/or delivering for the treatment of etc.) improvement and its
He is suitably to promote the quickly determining improvement for characterizing and/or treating.
Again, which can be by entity (for example, user, biological sample, treatment system including Medical Devices etc.)
It is converted to different state or things.For example, system 200 and/or method 100 can identify therapy to promote patient to change micro- life
Object group is pharmacogenomics spectrum, microbial population forms and/or Microbial functional diversity is to prevent and/or improve and resist
Raw element associated disease, to change the microbial population and/or health of patient.In another embodiment, which can incite somebody to action
It converts from the received biological sample of patient to (for example, by fragmentation, multiplex amplification, sequencing etc.) microbial population data set,
It can then be translated into feature relevant to antibiotic associated disease.For generating characterization model and/or treatment model.
In another embodiment, the technology can control treatment system with promote treatment (for example, by generate for treatment system into
The control instruction that row executes), thus convert treatment system.In another embodiment, the improvement of computer-related technologies can be with
The transformation of biological sample processing method is pushed, the primer subset compatible to relevant hereditary target, the genetic targets are such as selected
Mark is accredited as corresponding to microbial population pharmacogenomics feature (for example, relevant to antibiotic resistance or neurological susceptibility prominent
Become), microbial population composition characteristic and/or microbial population functional diversity feature relevant to antibiotic associated disease.
4th, which may be implemented including sample processing system, microbial population characterization system and multiple users
Functional creative distribution in network inside, wherein sample processing system can handle the life from multiple users simultaneously
Object sample (for example, in multiple mode) can use and characterize system for antibiotic related diseases by microbial population
Disease generates in personalized characterization and/or treatment (for example, being directed to the microbial population (micropopulation of such as user of user
It is pharmacogenomics spectrum, medical history, demography, behavior, preference etc.) customization).
5th, the technology can improve at least with microbial population digital medical, general digital medication (digital
Medicine generally), the computation modeling of gene sequencing and/or the related antibiotic associated disease of other related fieldss
Technical field.6th, which can use dedicated computing equipment (for example, with sample processing system (such as sequencing system；It is micro-
Biotic formation characterizes system；Treatment system etc.) relevant equipment) determine and handle the microbial population data for being used for characterization
Collection, and/or determine the treatment to antibiotic associated disease.However, the technology is using for microbial population characterization and/or tune
Any other suitable benefit can be provided in the case where the non-universal computer system of section.
3, system
The processing system 210 of system 200 can be used for receiving and handling (for example, fragmentation, amplification, sequencing etc.) biological sample
Product.Processing system 210 can be additionally or alternatively used for (such as by mail delivery system and/or other suitable processes)
Sample reagent box is provided and/or collected for multiple users (for example, response for the purchase order of sample reagent box 250)
250 (e.g., including it is configured to receive the container of biomaterial, illustrating for self sampling process is instructed to user).
In some embodiments, sample reagent box 250 may include material and related description for user with from one or more
Sample is collected (for example, swabbing by cotton swab in a collection position；Fluid suction；Biopsy etc.).Collect position can with
It is lower one or more of related: female sex organs, male sex organ, rectum, alimentary canal (gut), skin, oral cavity, nose, any
Mucous membrane and/or any other suitable sample provide position (for example, blood, sweat, urine, excrement, sperm, vaginal secretion
Object, tears, tissue sample, interstitial fluid, other body fluid etc.).Processing system 210 can additionally or alternatively include prepared by library
System and/or any suitable component, the library preparation system can be operated to prepare biological sample automatically (for example, using
The compatible primer of nucleic acid sequence relevant to antibiotic associated disease carries out fragmentation and/or amplification (such as with multiple form
Deng)) by sequencing system (for example, next-generation microarray dataset) sequencing.However, processing system 210 and associated component can be to appoint
What suitable mode configures.
The microbial population characterization system 220 of system 200 can be used for determining and/or analyzing anti-for characterizing and/or determining
The microbial population data set and/or supplementary data set of the treatment of raw element associated disease.In a variant, microbial population table
The rule that sign system 220 can obtain and/or appliance computer executes is (for example, feature selecting is regular；Model create-rule；Make
User's preference rules；Data storage, retrieval and/or display rule；Microorganism sequence create-rule；Sequence alignment rule；And/or
Any other suitable rule).However, microbial population characterization system 220 can configure in any suitable manner.
The treatment system 230 of system 200 is for promoting to user (for example, subject；The nursing provided conducive to treatment mentions
Donor etc.) to treat antibiotic associated disease (for example, reducing the risk of illness；By the microbial population drug base of user
Change into because group learning spectrum vulnerable to the state, etc. that can treat treatment for diseases for antibiotic) one or more of treatments.Treatment
System 230 may include any one in following item or more: communication system is (for example, by notifying caregiver to convey
Treatment recommendations (such as pass through interface 240), to recommend and/or provide treatment；Being capable of tele-medicine etc.), can be in user's equipment
The application of upper execution is (for example, for promoting the antibiotic associated disease application for the treatment of；Drug reminder application；Can operatively with
The application program etc. communicated with automatic drug distributor), (such as antibiotic (e.g., type, dosage, the medication of antibiotic therapies related thereto
Plan etc.)), auxiliary medical equipment is (for example, pill dispenser；Antibiotic medication device is (such as the anti-of local delivery
Raw element applicator, biodegradable antibiotic delivery system, not biodegradable antibiotic delivery system, antibiotic delivery
Agent, rice grain delivery system, stent delivery system, bead delivery system, controlled release equipment, elution equipment and/or other are suitable
Medicament delivery device；Diagnostic device for antibiotic associated disease；Etc.), user's equipment (e.g., including biometric
Sensor) and/or any other suitable component.One or more treatment systems 230 preferably can be by microbial population table
Sign system 220 controls.For example, microbial population characterization system 220 produces control instruction and/or notice to be sent to treatment system
With activation and/or in other ways, operation treatment system is used to promote treatment system 230.However, treatment system 230 can be with any
Other modes configuration.
As shown in Figure 10, system 200 can include additionally or alternatively interface 240, and interface 240 can be used for improving antibiosis
Plain relevant information is (for example, the characterization of antibiotic associated disease；Treatment recommendations；Compared with other users；As shown in figure 11,
Assessment to related treatment is composed with microbial population pharmacogenomics；As shown in figure 9, microbial population forms；Microorganism
Group be functional diversity etc.) display.In another embodiment, interface 240 can show antibiotic-related information, including micro-
Biotic formation forms (for example, sorting group), functional diversity (for example, the related base of function relevant to antibiotic associated disease
The relative abundance etc. of cause), and/or one or more of antibiotic associated diseases for user risk (such as relative to
The user group of shared Demographic is (for example, the patient of shared illness, smoker, person taking exercise, different diet programs make
User, the consumer of probiotics, antibiotic usage person, the group for carrying out specific treatment etc.)).In another embodiment,
Interface 240 can be used for that antibiotic-related information is presented, and treat the microbial population drug with antibiotic associated disease including being related to
Genomics spectrum (and/or microbial population composition, microbial population functional diversity etc.) changes with time.It is specific at one
In embodiment, interface can be operated to improve and can treat the relevant antibiotic of illness with antibiotic, and be based on user relative to
It shares the comparison between user's microbial population pharmacogenomics spectrum of the user group of Demographic and obtains
The display of relevant information.It, can be by selection (for example, based on the characterization for meeting threshold condition in another specific embodiment
Component；It is composed with the microbial population pharmacogenomics for the matched user of reference spectrum for being more than threshold similarity；More than threshold
The disease risk relevant to antibiotic of value；Other trigger events etc.) and antibiotic-related information subset presentation (for example, prominent
Show and/or otherwise emphasize the subset of antibiotic-related information out) antibiotic-related information at the interface Lai Gaishan it is aobvious
Show.However, interface 240 can show any suitable information, and can configure in any suitable manner.
The component of system 200 and/or system 200 can completely or partially by the execution of following item, trustship (host on),
Logical and/or including following item with following item: remote computing system is (for example, server, at least one networked computing system, ill-mannered
(stateless) of state, stateful (stateful)), local computer system, database is (for example, user's database, micro-
Biotic formation data set database, antibiotic associated disease database, treatment data library etc.), user's equipment (for example, use
Person's smart phone, computer, laptop, auxiliary medical equipment, wearable Medical Devices, caregiver's equipment etc.) and/
Or any suitable component.For example, system 200 may include computing system, can operate with processing system 210 (for example,
The next-generation microarray dataset of processing system 210) it communicates to execute the desired part of method 100 (such as to determine that microbial population medicine
Object genomics data).Although the component of system 200 is generally described as different components, they can be with any side
Formula physically and/or logically assembles.For example, smart mobile phone application can execute microbial population characterization partially or completely
System 220 (for example, generate the characterization of antibiotic associated disease using characterization model in real time；Biological sample is sequenced；Handle micro- life
Object sequence；Feature etc. is extracted from microbial population data set) and treatment system 230 (for example, the calendar application with smart phone
Interprogram communication takes antibiotic etc. according to the parameter determined by antibiotic treatment model to notify user).In addition it or can replace
The functionality of Dai Di, system 200 can also be distributed in any suitable manner between any suitable system component.However,
The component of system 200 can configure in any suitable manner.
4, method
As seen in figs. 1 a-1b, for the microbial medicine genomics of user relevant to antibiotic associated disease
The embodiment of method 100 can include: microbial population Drug Discovery is determined based on the biological sample gathered from subject
Learn at least one S110 of data set, microbial population composition data collection and microbial population functional diversity data set；It receives
Supplementary data set relevant at least one subset of this group of subject, wherein the supplementary data set provides the anti-of the subject group
The information S120 of raw element associated disease；Based on supplementary data set and from microbial population pharmacogenomics data set, micro- life
Object group is the feature progress and antibiosis that at least one of composition data collection and microbial population functional diversity data set extract
The related characterization process S130 of plain associated disease.The embodiment of method 100 can additionally or alternatively include determining treatment
(for example, with antibiotic treatment model), be configured as adjusting bacterial abundance in the subject according to characterization process characterization,
Distribution, functional diversity and/or pharmacogenomics diversity S140；Biological sample S150 is received from user；Based on processing
Microbial population pharmacogenomics data set, microbial population composition data collection and the micro- life of biological sample from user
Object group is that at least one of functional diversity data set carrys out the relevant to antibiotic associated disease of identification and utilization characterization process
The characterization S160 of user；Promote the treatment to subject (for example, antibiotic based on the characterization (for example, with model etc. is treated)
Treatment, behavior) S170；And based on processing biological sample, monitoring in different time points to the validity of the treatment of subject, with
Assess at least one of microbial population pharmacogenomics spectrum, microbial population composition and microbial population functional diversity
S180.Therefore, method 100 can be used for Treatment monitoring, and can be potentially served as the characterization as intermediate steps, especially
For assessing one or more of antibiotherapies.
4.1, method-processing data set
Frame S110 is recorded: micro- life of each biological sample in the set of characterization biological sample relevant to subject group
Object group is composition, function and/or pharmacogenomics, to generate the microbial population Diversity for subject group
At least one of data set, microbial population functional diversity data set and microbial population pharmacogenomics data set.Frame
S110 is used to handle each biological sample in the set of biological sample, with determining micro- life with each of subject group
In terms of object group is relevant composition aspect, function and/or in terms of pharmacogenomics.Composition aspect, function aspect and/or drug
May include in terms of genomics microorganism level composition in terms of, including with boundary, doors, classes, orders, families, genera and species, subspecies, strain
And/or any other suitable infraspecies taxonomy group (for example, as every group of total abundance, every group of relative abundance, shown in group
It is measured in sum etc.) the relevant parameter of microbial profile.In terms of composition aspect, function and/or pharmacogenomics side
Face can also be indicated with operating taxa (OTU).And/or it can be another in terms of pharmacogenomics in terms of composition aspect, function
Outside or alternatively in terms of the composition including genetic level (for example, passing through Multilocus sequence typing, 16S rRNA sequence, 18S
The area that rRNA sequence, ITS sequence, protein coding sequence, other genetic markers, other systematic growth markers etc. determine
Domain).It may include existence or non-existence and specific function (example in terms of composition aspect, function and/or in terms of pharmacogenomics
Such as, enzymatic activity, transport function, immunocompetence, antibiotics resistance gene etc.) relevant gene or the gene amount.Therefore, may be used
To use the output of frame S110 to come for the characterization process of frame S130 and/or the therapeutic process of frame S140 and/or the method 100
Other desired parts target signature is provided, wherein the feature can be (for example, bacterium belong to presence) based on microorganism,
Based on heredity (for example, expression based on specific genetic region and/or sequence), based on function (for example, there are specific catalysis
Activity), (such as codon mutation, Exon deletion or substitution, gene rearrangement, transposition etc.) based on pharmacogenomics, and/
Or be otherwise configured to.
Additionally or alternatively, frame S130 (for example, feature relevant to frame S130) may include but be not limited to: living with biology
The metabolism of property molecule or the relevant nucleotide region of resistance or any other nucleotide source functional character (for example, structure or
Adjust RNA, mRNA, protein or peptide).Particularly, bioactive molecule may include but be not limited to: antibiotic, antibody, peptide,
Hormone and any other endogenous or exogenous molecules, no matter its source (for example, diet, environment).In a variant, method 100
May include to any amount of user (for example, for individual user, for subject set (such as subject group
Body)) one or more complete macro genomes are expanded (for example, being used for the macro gene order-checking of complete microorganism；Draw with utilizing
Object is opposite；It is combined with primer).In a particular embodiment, method 100 may include: and gather to collect biological sample from user
(including self sampling from user)；Processing (for example, separate, amplification, be sequenced, than equity) carrys out the complete of biological sample
Macro genome；Determine that microbial population data set, microbial population Diversity Characteristics, microbial population functional diversity are special
Microbial population of seeking peace pharmacogenomics feature (for example, generality etc. of gene relevant to antibiotic resistance or neurological susceptibility)
At least one of；Based on feature (and/or microbial population data set) determine characterization (for example, antibiotic associated disease) and/
Or treatment.However, it is possible to handle complete macro genome in any suitable manner.
In some variations (for example, under the background of clinical diagnosis and treatment), frame S110 can be additionally or alternatively
Including analysis and processing environment sample (for example, the hospital environment from subject, home environment from subject etc.), in order to
The characterization and/or treatment model of the subsequent blocks of notification method 100.It is, for example, possible to use the mirror of the microorganism in subject's environment
It is fixed to notify treatment model, to promote to treat, the micro- life of nocuousness that the treatment is present in subject's prevention in subject's environment
Species type.However, environmental sample can be used in any other suitable manner to support method 100.
In some variations, the sample treatment in frame S110 may include any one or more in the following terms:
Cracking biological sample, the cell membrane for destroying biological sample separate unexpected component (for example, RNA, albumen from biological sample
Matter), the nucleic acid (for example, DNA) in purifying biological sample, amplification (for example, utilizing library preparation system) come biological sample
Nucleic acid, be further purified biological sample amplification nucleic acid and the nucleic acid of the amplification of biological sample is sequenced.
In some modifications of frame S110, amplification is carried out to the nucleic acid of purifying and preferably includes one carried out in the following terms
Or more: based on the technology of polymerase chain reaction (PCR) (for example, Solid phase PCR, RT-PCR, qPCR, multiplex PCR, drop
Fall formula PCR, nano PCR, nest-type PRC, heat start PCR etc.), helicase dependent amplification (HDA), ring mediate isothermal duplication
(LAMP), self-sustained sequence replication (3SR), the amplification (NASBA) based on nucleic acid sequence, strand displacement amplification (SDA), rolling circle amplification
(RCA), ligase chain reaction (LCR) and any other suitable amplification technique.It is used when expanding purified nucleic acid
Primer be preferably selected to prevent or minimize amplification deviation, and be configured as amplification of nucleic acid region/sequence (for example,
The region 16S, the region 18S, the region ITS, antibiotics resistance gene etc.), taxology, phylogenetics, diagnosis, preparation are provided
(for example, probiotics preparation), treatment aspect information and/or be used for any other suitable purpose.It therefore, can be in amplification
(for example, being used for the F27-R338 primer sets of 16S rRNA, 16S to be used for using the universal primer for being configured to avoid expanding deviation
F515-R806 primer sets of rRNA etc.).The primer of selection can additionally or alternatively with one or more antibiotic related diseases
Disease, microbial population pharmacogenomics feature is (for example, microbial population relevant to antibiotic effect is mutated compatible primer
(point mutation in gyrA gene and/or parC gene) etc.), microbial population composition characteristic is (for example, with hereditary target phase
The identified primer held corresponds to the relevant micro- life of taxonomical unit set relevant to one or more of sexually transmitted diseases
Object group is composition characteristic etc.), functional diversity feature, complementary features and/or other features relevant to antibiotic associated disease
Associated (such as compatible with hereditary target).For example, primer can hereditary target-complementary relevant to feature (for example, being come from
The genetic sequence etc. of relative abundance feature).In a specific embodiment, method 100 may include: to be determined based on following manner
Microorganism sequence: the primer of relevant to the antibiotic associated disease nucleic acid sequence of identification, will be originated from it is relevant with user's set
The nucleic acid material fragmentation of biological sample, and the nucleic acid material based on primer amplification fragmentation is (for example, flat using next-generation sequencing
The multiplex amplification etc. of the bridge amplification substrate of platform)；Determine microorganism sequence with and the related reference nucleic acid of antibiotic associated disease
Sequence group comparison (e.g., including microbial population pharmacogenomics biomarker relevant to antibiotic associated disease
Deng)；And microbial population pharmacogenomics data are determined based on the comparison.The primer used in some modifications of frame S110
Can additionally or alternatively include it is special to each biological sample assemble bar code sequence, can be in order to after amplification
Identify biological sample.It can include additionally or alternatively joint area for the primer in some modifications of frame S110, this connects
Head region is configured to and is related to sequencing technologies (for example, Illumina is sequenced) cooperation of acomplementary connector.Additionally or alternatively,
Any other step for being configured as promotion processing (for example, using Nextera kit) can be implemented in frame S110.
In some modifications of frame S110, carrying out sequencing to purified nucleic acid may include being related to targeting amplicon sequencing
And/or the method for macro gene order-checking, implementation technology includes one or more of the following terms: the side Bian Hecheng sequencing technologies
(for example, Illumina is sequenced), capillary sequencing technologies (for example, Sanger is sequenced), pyrosequencing techniques and nano-pore are surveyed
Sequence technology (for example, using Oxford nano-pore technology) or any other suitable sequencing technologies.
In a specific embodiment of frame S110, the nucleic acid of the biological sample in biological sample set is carried out
Amplification and sequencing include: Solid phase PCR, are related to the DNA fragmentation of the bridge joint amplification biological sample in the substrate with oligomerization connector,
Wherein amplification is related to having following sequence of primer: positive index sequence is (for example, flat corresponding to MiSeq/NextSeq/HiSeq
The Illumina forward direction of platform indexes), positive bar code sequence, transposase sequence is (for example, correspond to MiSeq/NextSeq/
The swivel base enzyme binding site of HiSeq platform), connector (for example, be configured as reduce homogeney and improve sequence results zero alkali
The segment of base, a base or two bases), other randomized bases, for targeting particular target (for example, the area 16S rRNA
Domain, the region 18S rRNA, the region ITS, antibiotics resistance gene etc.) sequence, reverse indexing sequence is (for example, correspond to
The Illumina reverse indexing of MiSeq/NextSeq/HiSeq platform) and reversed bar code sequence.In the particular embodiment,
Sequencing include using while sequencing while synthetic technology Illumina sequencing (for example, using HiSeq platform, using MiSeq platform,
Use NextSeq platform etc.).
In some variations, the calculation processing in frame S110 may include any one or more in the following terms:
Identify the sequence (for example, opposite with subject's sequence and pollutant) in microbial population source；To the sequence in microbial population source
Column are compared and/or are positioned (for example, being compared using single end, without vacancy comparison, comparison of having vacant position, pairing and/or other conjunctions
One or more of suitable technology (for promoting the comparison of reference sequences relevant to antibiotic associated disease) etc.
The sequence of fragmentation is compared)；And feature is generated, the feature derives from microbial population relevant to biological sample
Composition in terms of, in terms of function and/or in terms of pharmacogenomics.
About frame S110, after identifying the shown group of microorganism of microbial population associated with biological sample,
The generation of feature in terms of the composition from microbial population associated with biological sample can be executed and in terms of function.One
In a modification, generating feature may include generating feature based on Multilocus sequence typing (MSLT) to can be used for identify in method
The marker characterized in 100 subsequent blocks.Additionally or alternatively, generating feature may include generating description existence or non-existence
The feature of ratio between certain sorting groups of microorganism and/or the sorting group of microorganism shown.Additionally or alternatively
Ground, generating feature may include generating at least one of the feature of one or more of description the following terms: point shown
The quantity of class group, the sorting group shown, the network of functional group and/pharmacogenomics group, the different classifications group, the functional group that show
Interaction between the correlation of/pharmacogenomics group, different classifications group, the product generated by different classifications group, by
The ratio between the interaction between product, dead microorganism and the microorganism of work that different classifications group generates is (for example, right
In different shown sorting groups, the analysis based on RNA), systematic growth distance (for example, according to Kantorovich-
Rubinstein distance, Wasserstein distance etc.), any other suitable feature relevant to sorting group, any other conjunction
Suitable hereditary feature or functional character, any other suitable pharmacogenomics feature.
About frame S110, additionally or alternatively, generating feature (such as microbial population data set) may include
Such as using sparCC method, using genome relative abundance and mean size (GAAS) method and/or using genome it is opposite
Abundance generates the feature of the relative abundance of description different microorganisms group system using theoretical (GRAMMy) method of mixed model, wherein
GRAMMy method carries out the maximum likelihood assessment of a group or more groups of microorganism relative abundances using sequence similarity data.
Additionally or alternatively, generating feature may include generating the statistics measurement of the Classification Change as being originated from abundance measurement.In addition
Or alternatively, generating feature may include generating to be originated from the relative abundance factor (for example, the Plantago fengdouensis phase with taxonomical unit
Close, the Plantago fengdouensis of the taxonomical unit influences the abundance of other taxonomical units) feature.Additionally or alternatively, feature is generated
It may include the existing qualitative features for individually and/or in combination generating one or more sorting groups of description.In addition it or can replace
Dai Di, generating feature may include generating spy relevant to genetic marker (for example, representativeness 16S, 18S and/or ITS sequence)
Sign, the genetic marker characterize the microorganism of microbial population relevant to biological sample.Additionally or alternatively, it generates special
Sign may include generating to specific gene and/or the relevant feature of the function association of the organism with specific gene.In addition or
Alternatively, generating feature may include generating and the pathogenic of taxonomical unit and/or to belong to the product of taxonomical unit related
Feature (for example, for gene, genomic island marker etc. of virulence factor).Additionally or alternatively, generating feature can be with
Including generating feature relevant to the pharmacogenomics marker of target classification unit (for example, detection resists with any kind of
The relevant gene of life element resistance and/or mutation).
However, the frame S110 and/or other desired parts of method 100 can include generating to be originated to the nucleic acid of biological sample
Any other suitable feature of sequencing and positioning.For example, one or more features can be associativity (for example, relating to
And body, triplet in pairs), relevant (for example, correlation in relation to) between different characteristic, and/or have with the variation of feature
It closes (for example, the variation of time change, sample sites, spatial variations etc.).However, frame S110 can also be in any suitable manner
It carries out.
Frame S120 is recorded: receiving supplementary data set associated at least one subset that the subject gathers, the supplement
Data set provides the information S120 of the antibiotic associated disease of subject set.Frame S120 gathers for obtaining with the subject
In the relevant additional data of one or more subjects, can be used for training (train) and/or verifying raw in frame S130
At characterization process.In frame S120, supplementary data set preferably include from investigation data, but can in addition or can
Alternatively include any one or more in the following terms: being originated from sensor and/or other appropriate components (for example, system
200 component can include therapeutic equipment, user's equipment etc.) multi-faceted data, medical data is (for example, current and history
Medical data (such as antibiotic medical history)), the data information of antibiotic associated disease is with the presence or absence of illness, correlation (for example, examine
Disconnected, associated treatment, instruction of progress over time etc.) and/or any other suitable type data.It is including receiving
In some modifications of the frame S120 of the data of investigation, preferably provided from the data of investigation relevant to subject
Physiologic information, demographic information and behavioural information.Additionally or alternatively, frame S110 and frame S120 can be with 2016 4
Similar mode carries out in the U.S. Patent Application No. 15/097,862 that the moon is submitted on the 13rd, and the U.S. Patent application is whole by quoting
Body is incorporated herein.However, processing supplementary data set frame S120 can be carried out in other ways.
4.2, characterization processing is carried out
Frame S130 is recorded: based on supplementary data set and from microbial population pharmacogenomics data set, micropopulation
It is the feature that at least one of composition data collection and microbial population functional diversity data set extract, carries out and antibiotic phase
Close the relevant characterization process S130 of illness.As shown in figure 3, frame S130 can be used for identification mark and/or feature combination, this feature
And/or microbial population composition, functional character and/or pharmacogenomics feature of the feature combination based on subject can be used to table
Levy subject or group.Therefore, characterization process is used as diagnostic tool, can be based on the microbial population group of subject
Subject (for example, in terms of) is characterized at, functional character and/or pharmacogenomics feature.It then can be with
Suggest or provide personalized antibiotherapy (and/or other therapies) using this characterization by the treatment model of frame S140.
When executing characterization process, calculation method is can be used (for example, statistical method, machine learning method, people in frame S130
Work intelligent method, bioinformatics method etc.) subject is characterized as to show to have the feature of the subject group of health status
Property feature, which can pass through personalized therapy program (for example, personalized regimen of antibiotics) effectively treatment.?
In some modifications of frame S130, execute characterization process may include generate one or more of antibiotic associated diseases one kind or
More kinds of characterizations.In embodiment, the characterization process of frame S130 can contribute to identification with antibiotic associated disease and with micro- life
Object group is pharmacogenomics spectrum (for example, microbial population pharmacogenomics feature relevant to antibiotic associated disease；
Deng), micropopulation is (for example, microbial population pharmacogenomics feature, taxology group, microbial population composition characteristic
Deng), microbial population functional diversity (for example, with the cluster/capital of a country gene and genomics approach of ortholog group encyclopedia,
Microbial population functional diversity feature etc. is related) and/or other properly relevant up-regulations of aspect relevant to microbial population
Or the correlation between lowering.Characterization up-regulation and/or lower can it is horizontal for any suitable taxology (for example, boundary, door, guiding principle,
Mesh, section, genus and species, strain), any suitable functional diversity granularity, any suitable microbial population pharmacogenomics spectrum
Granularity and/or with any suitable granularity (for example, chromosome, locus, gene, allele, locus, gene, nucleosides
Acid etc.).
In another modification, in frame S130 characterize antibiotic associated disease may include production diagnostic analysis (for example,
Assess the risk as caused by antibiotic associated disease；Calculate the variation of the risk assigned by the treatment identified；Diagnosis exists
Or antibiotic associated disease (such as presence or absence of microbial population pharmacogenomics feature) is not present；Diagnosis is related to micro- life
Object group is the severity of the antibiotic associated disease of pharmacogenomics, composition and/or functional diversity at any time；To such as
Resistance and/or neurological susceptibility of the treatment of antibiotic etc.) and/or other analyses.In another modification of frame S130, antibiosis is characterized
Plain associated disease can be based on one or more supplementary data sets.For example, feature selecting rule set can will be one or more of
Kind antibiotic associated disease is associated with one or more of biometric features, and the biometric features sources provide antibiosis certainly
Plain associated disease information biometric data (for example, with diagnosis stranguria syndrome, another sexually transmitted disease, urinary tract infections and/or its
The relevant optical data of his suitable antibiotic associated disease；The data associated with auxiliary medical equipment collected are (such as logical
Cross the antibiotic delivery parameter of antibiotic delivery equipment)；Supplementary data relevant to sample acquisition position；Blood data；Temperature
Data；User's behavioral data；Cardiovascular data；Excrement data；Deng).In another embodiment, supplementary data set can wrap
Include the biography collected at user's equipment, auxiliary medical equipment and/or other suitable components (for example, sample processing system etc.)
Sensor data.In another embodiment, carry out characterization process may include determined based on the treatment promoted at any time it is a series of
Characterization at any time is (for example, treatment data includes regimen of antibiotics data, probiotics protocol and/or and user
Other associated suitable treatment datas of group), wherein the effect of different treatment at any time can help to illustrate and antibiotic
The relevant microbial population pharmacogenomics of associated disease, microbial population composition and/or the relevant opinion of functional diversity.
However, executing characterization process based on supplementary data set, and/or generation diagnostic analysis can carry out in any suitable manner.
Frame S130 can additionally or alternatively generate feature, and the frame S130 is for generating for characterizing process (for example, raw
At the purposes of characterization model) and/or other suitable processes for method 100 one or more features.Feature can be with
Including any one or more in the following terms: microbial population pharmacogenomics feature, microbial population composition are special
Sign (for example, absolute abundance and/or relative abundance of the sorting group in the microbial population of user), microbial population function are more
Sample feature and/or other suitable features.Microbial population pharmacogenomics feature may include and following one or more
The relevant feature (for example, illness relevant to antibiotic, relevant taxonomical unit, relevant functional diversity etc.) of item: password
Sub- mutation, Exon deletion, substitution, gene rearrangement, transposition, microbial strains mutability, microbial strains are to antibiotic
Resistance or neurological susceptibility, microbial strains are total to dependent behavior, microbial medicine genomics marker and/or any other is suitable
Feature (for example, relative abundance etc. of these features).Microbial population functional diversity feature may include appointing in the following terms
What is one or more: capital of a country gene and genomic encyclopedia (KEGG) functional character are (for example, related to flagellum biosynthesis
KEGG feature etc.), the cluster (COG) of the ortholog group of protein characteristic, feature, genome functions derived from L2, L3, L4 it is special
Sign, functional character, chemical functional feature specific to and/or sorting group related to sorting group (for example, cysteine be metabolized etc.),
Whole body functional character is (for example, general immunity function；Function relevant to systemic disease etc.), and/or any suitable function
Feature.Microbial population feature can be additionally or alternatively derived from and/or related at least one of the following: relatively rich
Spend monotonic transformation, nonmonotonic transform, normalization, such as derived from linear latent variable analysis and non-linear latent variable analysis in
The feature vector of at least one, linear regression, nonlinear regression, kernel method, feature embedding grammar, machine learning, statistics push away
Disconnected method and/or any other suitable method.
About frame S130, it is based preferably on according to one or more computer implemented rules (for example, feature selecting is advised
Then, user's preference rule etc.) microbial population data set is handled to determine feature, but any suitable information can also be based on
Determine feature.For example, method 100 may include obtaining feature selecting rule set (for example, microbial population pharmacogenomics are special
Sign selection rule etc.), by antibiotic associated disease and microbial population pharmacogenomics feature, microbial population composition characteristic
And/or the subset (for example, coming from potential microbial population feature database) of microbial population functional diversity feature is associated；And
And feature is generated based on for this feature selection rule set assessment microbial population data set, the wherein antibiotic correlated characteristic
Selection rule set can operate with improve microbial population tag system (for example, by promote reduced processing time (such as with
In conversion supplementary data and feature into characterization model)；By improving model storage, retrieval and/or the speed executed；Pass through improvement
Characterization and/or treatment provide accuracy).In a specific embodiment, feature selecting rule can be with microbial population medicine
Correlation between object genomics feature and the antibiotic effect for being related to one or more of antibiotic associated diseases is associated
(for example, wherein in the microbial population pharmacogenomics spectrum of user, microbial population composition and/or microbial population function
In the case where energy diversity etc., correlation can be determined based on a series of user's biological samples of processing as time goes by
To assess antibiotic effect).
The rule that the other parts of frame S130 and/or method 100 preferably include appliance computer realization carrys out processing colony
Grade data, but can also additionally or alternatively include the rule of appliance computer realization to handle micro- life on the basis of following
Object group is related data: the distinctive basis of demography is (for example, shared Demographics is (such as related to antibiotic
Illness and/or history antibiotic treatment are using relevant medical history, race, age, or sex etc.) subgroup)；The distinctive basis of illness
The distinctive basis of (for example, show specific from the subgroup of antibiotic associated disease), sample type is (for example, using different meters
Calculation machine realize rule come handle from it is different collection positions collect samples microbial population data；Based on can be used for supplementing
The different computer implementation rule etc. of the type application of the supplementary data of sample) and/or any other suitable basis.In this way,
Frame S130 may include that the user in user group is distributed to one or more subgroups；And apply different computers
The rule of realization determines the feature of different subgroups (for example, used characteristic type collection；The characterization model generated by feature
Type etc.).However, the rule that appliance computer is realized can be executed in any suitable particle size fraction in any suitable manner.
In a variant, frame S130 may include using feature selecting rule (for example, such as exhaustive, best preferential, mould
Quasi- annealing, positive greedy, reversed greedy and/or other suitable feature selecting algorithms) to be filtered, sort and/or with it
His mode select for generate one or more characterization models, treatment model (for example, using by one or more treatment with
Different degrees of effect, with microbial population pharmacogenomics spectrum, microbial population composition, microbial population functional diversity
And/or the associated rule such as other suitable aspects) and/or other appropriate models feature.In a variant, feature
The application of selection rule can cause the relevant opinion of microbial population, and be based on this in sample treatment (for example, technology, experiment
Condition, frame S110-S120, S150 etc.) in be changed.For example, method 100 may include: to select using antibiotic correlated characteristic
Select rule set with identify (for example, most related etc.) related to antibiotic associated disease feature (for example, in the presence of, risk, treatment
Deng)；And the primer for selecting hereditary target relevant to the feature of identification compatible is (for example, for expanding and being sequenced to generate micro- life
Object group is data set etc.).In this way, as shown in figure 12, in addition feature selecting rule and/or other computer implemented rules can be
Or it is alternatively used for determining sample treatment parameter (for example, about frame S110-S120, the description such as S150).However, it is possible to appoint
Where formula defines one or more feature sets using the feature selecting rule of any suitable quantity and/or type.
In one embodiment, in frame S130, feature selecting rule may include gathering using for the first subject
The statistical analysis (for example, analysis of probability distribution) of similitude and/or otherness between the second subject set.Described
One subject set shows dbjective state (for example, antibiotic associated disease state)；Second subject set does not show mesh
Mark state (for example, " normal " state).When implementing the modification, Kolmogorov-Smirnov (KS) can be used and examine, arrange
Column are examined, Cram é r-von Mises is examined and any other statistical test is (for example, t is examined, Wei Erqi t is examined, z inspection
Test, Chi-square Test, it is relevant to distribution examine etc.) in it is one or more.Particularly, can be used it is one or more this
The feature set in subject as described below with different abundance is evaluated in the statistics hypothesis testing of sample: being shown and target-like
State is (for example, defective mode；Microbial population pharmacogenomics spectrum；Deng) the first subject set and do not show dbjective state
Second subject of (for example, normal condition) gathers.It more specifically, can be based on tested with the first subject set and second
Person gathers relevant percent abundance and/or any other suitable is related to multifarious parameter to constrain evaluated feature set
It closes, to increase or decrease the confidence interval of characterization.In a specific embodiment of the embodiment, feature can come from bacterium
Taxonomical unit, the division bacteria unit are largely deposited in the first subject set and the second subject set of certain percentage
, wherein can be determined by KS inspection the first subject set the second subject set between taxonomical unit it is relatively rich
Degree, indicates (for example, with p value) with conspicuousness.Therefore, the output of frame S130 may include showing conspicuousness (for example, p value is
0.0013) normalized relative abundance value is (for example, the relative abundance of taxonomical unit is higher than health volunteer in deceased subject
25%).Functional character, pharmacogenomics feature can additionally or alternatively be implemented or be originated to the modification that feature generates,
Or metadata feature (for example, non-bacterial marker).However, it is possible to apply any suitable statistics in any suitable manner
Analysis.
In another modification, frame S130 will can additionally or alternatively come from microbial population Diversity data
Collection, microbial population functional diversity data set, microbial population pharmacogenomics diversity data collection, supplementary data set,
And/or the input data of at least one of other suitable data sets is converted to feature vector, this feature vector can be pre-
Survey test efficacy in the characterization (for example, diagnosis) of subject group.Data from supplementary data set can be used additionally or alternatively
In provide characterization collection one or more characterizations instruction, wherein using the training dataset and candidate classification of candidate feature come
Training characterization process, to identify the feature and/or feature group that there is height (or low) predictive ability to accurately prediction classification
It closes.The refining so that identifying has height phase with the specific classification of subject to characterization process using training dataset as a result,
The feature set (for example, combination of Subject characteristics, feature) of closing property.
In the modification of frame S130, be effectively predicted the classification of characterization process feature vector may include in the following terms
One or more related features: microbial population diversity measurement (for example, about in each sorting group distribution, close
In the distribution in archeobacteria group, bacterium group, viral group and/or eucaryote group), the sorting group in the microbial population of one
Presence, the expression of specific genetic sequence (for example, 16S sequence), the micropopulation in one in the microbial population of one
The relative abundance of sorting group in system, microbial population adaptive metrology (for example, disturbance in response to being determined by supplementary data set),
Encode the protein or RNA (enzyme, transport protein, the protein for carrying out self-immunity systems, hormone, RNA interfering with given function
Deng) gene abundance and be originated from microbial population diversity data collection, microbial population functional diversity data set, micro- life
Object group is other suitable features of pharmacogenomics characteristic data set and/or supplementary data set.Additionally or alternatively, may be used
To use the combination of feature in feature vector, wherein can will be special when providing a part as feature set of assemblage characteristic
Sign grouping and/or measurement weight.For example, a feature or feature set may include the institute of the bacterium in the microbial population of one
The composition (weighted composite) through measuring weight of the number of classification is shown, is existed in the microbial population of one
Specific bacterium category shows specific 16S sequence and first bacterium relative to the in the microbial population of one
The relative abundance of two bacteriums.However, it is also possible to additionally or alternatively determine feature in any other suitable way
Vector sum feature.
Additionally or alternatively, frame S130 may include generating characterization model, be used for one or more based on application
Feature, microbial population data set, supplementary data and/or other suitable data come generate for one or more of antibiosis
One or more characterization models of plain associated disease.Characterization model (and/or treatment model or other suitable models) can be with
Including any one or more in the following terms: property of probability, enlightening property, certainty property and/or any other
Suitable property.The frame S130 of method 100 and/or other suitable parts (for example, generating treatment model S140) and/or system
200 can be used in algorithm described in the U.S. Patent Application No. 15/097,862 that on April 13rd, 2016 submits similar
The full content of one or more of algorithms, the U.S. Patent application is incorporated herein by reference, and/or can use any conjunction
Suitable algorithm.In a modification of frame S130, it can predict that (RFP) algorithm characterized to generate and train according to random forest
Journey, the algorithm is by bagging method (bagging) (that is, self-service set (bootstrap aggregation)) and from training dataset
Random character collection is selected to combine to construct decision tree set T relevant to random character set in conjunction.Using random forest
When algorithm, randomly selects N number of sample in decision tree set and be replaced to create the subset of decision tree, and for each
Node selects m predicted characteristics for being measured from whole predicted characteristics.Using at node (for example, according to target letter
Number) predicted characteristics of best bifurcated are provided to carry out bifurcated (for example, pitching (bifurcation), at node in node punishment two
Divide trident (trifuracation)).By concentrating repeatedly sampling from large data, in identification prediction classification in strong feature
The intensity of characterization process can greatly increase.It in this variant, can during processing include for guarding against deviations (for example, taking
Sample deviation) and/or lead to the measure of departure to increase the robustness of model.However, it is possible to carry out in any suitable manner
The application of these models.
In another modification of frame S130, can for different demography group (such as from different antibiotic medicines
The different characterization models etc. of the relevant user's subgroup of history), antibiotic associated disease (such as can treat different antibiotic
The different characterization models of illness；For the different characterization models etc. of different microbial population pharmacogenomics spectrums), individual
(the model vs as introduced the feature for being originated from biometric sensing data and/or investigating response data is only for subject, supplementary data
Stand on the model etc. of supplementary data) and/or other suitable standards generate different characterization models.As shown in fig. 6, can be used has
The characterization of different characterization model outputs is treated to determine and/or promote, such as by that will be originated from for different antibiotic associated diseases
The output of different characterizations be input in treatment model (for example, single being treated or multiple therapies are treated with generate customization
Different antibiotic associated disease etc.).
In another embodiment, frame S130 may include that different characterization models is selected for different user accounts；
And it for each user account, will be stored with the associated corresponding characterization model of user account, to improve data
Storage and/or retrieval (for example, process etc. for executing method 100).Generate the multiple characterization models for being suitable for varying environment
It can be by improving characterization accuracy (for example, by the demography, the antibiotic associated disease, spy that are directed to particular subject
The custom analysis such as sign), to the retrieval rate appropriate of the characterization model from database (for example, passing through the characterization mould that will be customized
Type is associated with specific user account and/or other identifier symbol), the generation of characterization model and/or execution be (for example, custom mold
The subclass of the relevant potential feature pool of type illness relevant to antibiotic is associated, and remaining non-selected feature and antibiotic
The lesser situation of associated disease correlation) and/or other suitable aspects of microbial population tag system provide to microorganism
Group is the improvement of characterization system.
In another modification of frame S130, generating can be with for the feature set of different characterization models (and/or other models)
Based on different feature selecting rules (for example, being pharmacogenomics feature selecting rule set with life using different microorganisms group
At the different characteristic collection specific to different sexually transmitted diseases；Deng).Alternatively, overlapping or same feature set selection rule can
For generating different characterization models (for example, using identical microbial population medicine when generating two different characterization models
Object genomics feature etc.).Additionally or alternatively, it can execute in any suitable manner and generate any amount of characterization mould
Type.However, executing characterization process S130 can carry out in any suitable manner.
4.2.A, method-antibiotic associated disease characterization
In one embodiment, the characterization process of the frame S130 based on statistical analysis can be without culture and/or implementation
The mode of self sampling of patient identifies have highest related with the disease of antibiotics-treatable (for example, sexually transmitted disease, STD)
Property feature set, thus it is significant reduce individual receive treatment time lag.In the specific embodiment of the embodiment, it is based on sample
Inhereditary material multiplex PCR and term in, the characterization process of frame S130 can be used as diagnostic test to identify and characterize sample
Present in gonorrhea strains and one or more following aspects: the mutability of bacterial strain is (for example, mutation type, mutation become
Gesture, mutation rate etc.), bacterial strain to the resistance of various types antibiotic, relative in subject presence or absence of other microorganisms
Bacterial strain total dependent behavior (for example, in terms of the interference of behaviour, in up-regulation in terms of, in terms of downward etc.), Yi Jiren
Other suitable aspects interested in the notification model what is provided for personalized treatment.Therefore, the characterization process energy of frame S130
Bacterial strain including STD (for example, stranguria syndrome) related microorganisms present in the hereditary feature characterization sample based on identification microorganism.
In the modification of frame S130, microbial population feature can be associated with Diplococcus gonorrhoeae (kind).In a spy
Determine in embodiment, microbial population feature may include taxonomical unit (for example, Diplococcus gonorrhoeae) gyrA gene and
The relevant point mutation feature of point mutation at least one (it can be related to ciprofloxacin resistance) of parC gene.At another
In specific embodiment, microbial population feature be can be and chimeric penA allele (it can be related with cephalosporin resistance)
There are correlations.This correlation and/or other suitable correlations between microbial population feature and therapeutic effect can be used for
Determine and/or promote treatment.However, any microbial population feature may include and any suitable taxonomical unit and/or confrontation
Any suitable resistance or the relevant any suitable microbial population pharmacogenomics feature of neurological susceptibility of raw element.With stranguria syndrome
And/or the relevant characterization of other suitable antibiotic associated diseases can additionally or alternatively with mention on April 13rd, 2016
The U.S. Application No. 15/097 of friendship, the similar mode of method described in 862 carry out, and this application will be incorporated by this by reference
Text.
4.3, method-personalization
Method 100 can additionally or alternatively include frame S140, and frame S140 is recorded: being determined and is configured to adjust according to characterization
Bacterial abundance, distribution, functional diversity and/or the multifarious treatment of pharmacogenomics in the subject of process characterization
S140.Frame S140 is for identifying and/or predicting that can correct or otherwise treat the antibiotic that subject has can treat
The therapy (for example, antibiotherapy scheme etc.) of illness.Frame S140 can additionally or alternatively include generating and/or using use
In the treatment model for determining treatment.In frame S140, treatment can be additionally or alternatively selected from including following one or more
The therapy of kind: the therapy based on antibiotic, the therapy based on probiotics (for example, as shown in Figure 8), antifungal therapy are based on
The therapy of bacteriophage, the therapy based on prebiotics, the therapy based on small molecule, therapy, diet therapies related thereto, office based on drug
Portion's therapy, cognition/behavior therapy, physical therapy, clinical treatment, the therapy based on alternative medicine, the therapy (example based on environment
Such as, the therapy based on light, therapy based on temperature etc.) and/or be designed to operate in any other suitable manner it is any its
His suitable therapy is (for example, promote health of the user about antibiotic associated disease；Etc.).Therapy based on antibiotic can
Including following any one or more: antibiotic (for example, penicillin, cephalosporin etc.) based on cell wall is based on bacterium
The antibiotic (for example, rifamycin, lipid mycin, quinolone, sulfonamides etc.) of enzyme, based on cell membrane antibiotic (for example,
Polymyxins etc.), the antibiotic based on sterilization, the antibiotic based on protein synthesis are (for example, macrolide antibiotics, woods
Can amides antibiotic, tetracycline etc.), cyclic annular lipopeptid, glycylcycline, oxazolidone, treatment relevant to auxiliary medical equipment
Method and/or other treatment system and/or any other suitably based on the therapy of antibiotic.
In the modification of frame S140, treatment model may include antibiotic treatment model comprising decision tree/decision diagram,
Decision tree/decision diagram is with the available antibiotic at prioritizing tree/figure node (for example, certain antibiotics type, antibiosis
Plain dosage etc.) to provide most suitable antibiotic and its dosage in each stage for the treatment of plan, as shown in Figure 4.Treatment stage
Arrange can based on to subject apply certain antibiotics treatment positive result (for example, to the beneficial bacteria of subject
The influence of group minimizes) and/or negative consequences (for example, risk of pernicious infection) tradeoff, it is thus early in treatment plan
The most effective but least harmful antibiotic of phase promotion targeting disease related strain.When traversing decision tree/figure branch, upper
Patient's instruction and/or result at trip node after administration of antibiotics can be used for promoting the application of the antibiotic at downstream node.
Alternatively, once treating patient, the further promotion of antibiotic treatment can be terminated, and the restorative of subject can be promoted to control
Treat (for example, the Probiotic supplement generated by the variation for the treatment of model).However, antibiotic treatment model may include any
Suitable property and/or any suitable algorithm of application determine any suitable aspect relevant to antibiotic treatment.
About frame S140, additionally or alternatively, the output of antibiotic treatment model may include prediction model, description pair
Subject applies the prediction result and/or consequence of different antibiotic treatment/dosage, and another entity is allowed to provide one or more
It makes decision when multiple antibiotic are to subject.It, like this can be based on following one or more of for subject for frame S140
Customize antibiotherapy: the illness (for example, in the presence of microbial strains relevant to disease) of subject；With the resistance of antibiotic
And/or the relevant microorganism hereditary sequence of neurological susceptibility；Abundance/propagation of bacterial strain relevant to subject's illness；The people of subject
Mouth statistics and/or behavioural characteristic；Other microbial populations of subject；The considerations of being obtained from subject's environment factor；With
Any other suitable factor.In the specific embodiment of the therapy based on bacteriophage, it can be used to shown in subject
Specific bacteria (or other microorganisms) has one or more groups of the bacteriophage of specificity (for example, falling to be formed with regard to set
For unit) lower or otherwise eliminate the groups of relevant to the disease of subject or illness certain bacteriums.Therefore, base
It can be used for reducing the size of unexpected bacterial flora (or other microorganisms) shown in subject in the therapy of bacteriophage.Supplement
The therapy based on bacteriophage can be used to increase the relative abundance for the bacterial community not targeted by used bacteriophage in ground.
In a variant, frame S140 and/or S170 may include automatic starting control treatment system to promote treatment
Signal (for example, based on characterization, treatment model output etc.), wherein enabling signal may include following one or more: generate
Control instruction and send it to treatment system (for example, control antibiotic delivery equipment is to provide antibiotic etc. to user),
Starting notice provides (for example, to notify user about one or more characterizations and/or treatment etc.), and/or control treatment
System is to promote any other the suitable operation treated.In another modification, frame S140 may include promote user with
Interaction between caregiver (for example, arrange the reservation with caregiver as shown in Figure 7；Channel is sent out by wireless communication
Play tele-medicine meeting etc.), such as in response to trigger event and/or with trigger event simultaneously (for example, characterization be more than threshold value with
Antibiotic associated disease risk；By user and/or caregiver's manual request；Based on point to the biological sample after treatment
Analysis is to identify the therapeutic effect etc. lower than threshold value).However, it is possible in any suitable manner to promote the interaction between user
Progress.
In the modification of frame S140, generate and/or application for the treatment of model can one based on antibiotic associated disease or
More reasons (for example, the reason of antibiotic associated disease risk), wherein determining treatment to drop by treatment model can be operated
The relevant state of an illness risk of low antibiotic.About frame S140, such as by being accredited as in the subject group in good health situation
Subject evaluated, can with identification " normal " or baseline microbial population composition characteristic, functional character and/or drug base
It relatively obtains medical treatment model because group learning a feature.It is characterized as being in the subject group in good health state once identifying
Subject's subclass (for example, using the feature of characterization process), can be generated in frame S140 towards in good health shape
Microbial population composition characteristic, functional character and/or the pharmacogenomics feature of the subject of state adjusts microbial population
The therapy of composition characteristic and/or functional character.Therefore, frame S140 may include identifying one or more of baseline microbial populations
Composition characteristic, functional character and/or pharmacogenomics feature are (for example, one kind for each of demography collection
Baseline microbial population) and potentially treatment preparation and therapeutic scheme, the potential treatment preparation and therapeutic scheme can make
The microbial population of subject in ecological disturbance state turns to identified baseline microbial population composition, function composition
And/or one of pharmacogenomics composition.However, treatment model can be generated and/or be refined in any other suitable way.
In a variant, frame S140 and/or S170 may include obtaining and microbial population pharmacogenomics (example
Such as, it is composed by microbial population pharmacogenomics and identifies that acquisition is intended to evade antibiotic resistance or attacks antibiotic susceptibility
Antibiotic treatment etc.), at least one of microbial population composition and/or functional diversity (for example, extract feature) correlation
Therapeutic combination (for example, antibiotic treatment).In one embodiment, method 100 can include determining that related to antibiotic
The regulator of the relevant biomolecule of illness is (for example, the life obtained from taxon set relevant to antibiotic associated disease
The regulator of object molecule)；The therapeutic combination of antibiotic associated disease is obtained based on regulator；And promote therapeutic combination.So
And determine and/or promote treatment that can be similar to the U.S. Application No. 15/097 submitted on April 13rd, 2016 with any, 862
Mode carries out, which is integrally incorporated by reference, and/or can be carried out in any suitable manner.
Method 100 can additionally or alternatively include frame S150, and frame S150 is recorded: receive biological sample from user.
Frame S150 can be used for promoting the generation of the microbial population data set for subject, can be used for obtaining characterization process
Input.In this way, receive, processing and analysis biological sample preferably facilitate for subject microbial group be data set generation,
It can be used for providing input for characterization process.Processing and analysis the biological sample from subject preferably with above for frame
The similar mode of one of embodiment, modification and/or the embodiment of S110 description carries out.Additionally or alternatively, processing biology
The method of sample can with the method that is similar in the U.S. Patent Application No. 15/097,862 submitted on April 13rd, 2016 into
Row, the U.S. Patent application are incorporated herein by reference in their entirety.However, biological sample in frame S150 receives and processing can
Alternatively execute in any other suitable manner.
Additionally or alternatively, method 100 may include frame S160, and frame S160 is recorded: characterization process be utilized, based on processing
The microbial population pharmacogenomics data set of biological sample from user, microbial population composition data are closed, and
At least one of microbial population functional diversity data set determines the characterization to subject.Frame S160 is used for from subject's
Feature is extracted in the data in microbial population source (for example, being based on computer implemented rule evaluation microbial population data
Collection), and the feature is used as to the characterization process described in above-mentioned frame S130 and/or during method 100 is any appropriate
Embodiment, modification or the input of embodiment.Therefore, identify that the characterization in frame S160 preferably includes identification and subject
Microbial population composition, function composition and/or the pharmacogenomics of microbial population sample form associated feature and/or
The combination of feature during the feature is input to characterization, and receives characterization subject and belongs to the next item down or more
The output of item: behavior group, gender group, diet group, morbid state group and any other that can be identified by characterization process are properly
Group.Frame S160 may further include generation and/or output confidence metric associated with the characterization to subject.Example
It such as, can be from the quantity of the feature for generating characterization, the relative weighting for generating the feature characterized or ranking, characterization process
In preference measurement and/or obtain confidence metric with any other suitable parameter associated in terms of characterization process.?
In some modifications, it can be obtained with the investigation from subject and/or medical history obtains feature to supplement from the micro- of subject
The feature extracted in biotic formation data set, the feature can be used for further refining the characterization process of frame S130.However, by
The microbial population data set of examination person can be used additionally or alternatively in any other suitable manner with Enhancement Method 100
Model, and frame S160 can be carried out in any suitable manner.
4.4, promote and monitor treatment
Additionally or alternatively, method 100 may include frame S170, and frame S170 is recorded: based on characterization (for example, and treatment
Model etc.) promote treatment (for example, antibiotic treatment etc.) to subject, frame S170 can be used for recommending and/or mentioning for subject
For personalized treatment, so that the microbial population of subject composition, functional character and/or pharmacogenomics feature are turned to reason
The equilibrium state thought.Frame S170 may include according to the microbial population of subject composition, functional character and pharmacogenomics
Feature provides customization treatment for subject, as shown in figure 5, wherein customization treatment is antibiotic formulations, which is matched
It is set to the illness that correction has the subject for identifying characterization.In this way, the output of frame S140 can be used for based on housebroken treatment
Model is directly the treatment preparation and scheme (such as dosage, operation instruction) that subject promotes customization.Additionally or alternatively, it controls
Treating offer may include recommending to be configured to make microbial population composition, functional character and/or pharmacogenomics feature to turn to
The available treatment measure of desired state.
Antibiotic treatment offer in frame S170 may include being provided to subject about recommendation treatment and/or other forms
The notice for the treatment of.In one embodiment, the web interface of personal computer associated with subject or laptop can be with
Access of the subject to the user account of subject is provided, wherein user account include about user characterization, use
The detailed characterizations of the microbial population various aspects of person, and about the recommended therapy measure generated in frame S140 and/or S170
Notice information.In another embodiment, in personal electronic equipments (for example, smart phone, smartwatch, wear-type intelligence
Can equipment) on the application that executes can be configured to provide notice (for example, display, tactile, with audible means etc.), this is logical
The treatment recommendations that MS is generated in the treatment model by frame S170.Notice and/or probiotic therapy can be additionally or alternatively
Ground is straight by entity relevant to subject (for example, caregiver, spouse, important other people, health care professionals etc.)
Offer is provided.In some further modifications, notice can additionally or alternatively be provided to the associated reality of subject
Body (for example, health care professionals), wherein the entity can apply remedy measures (for example, passing through prescription, by being controlled
Treat meeting etc.).However, it is possible to provide the notice for the treatment of application to subject in any other suitable manner.
Additionally or alternatively, method 100 may include frame S180, and frame S180 is recorded: based on processing biological sample, monitoring
In different time points to the validity of the treatment of subject, to assess microbial population pharmacogenomics spectrum, microbial population
At least one of composition and microbial population functional diversity.Frame S180 can be used for controlling for the given subject characterized
The additional data that model collection is treated about the good effect of probiotic therapy, counter productive and/or shortage validity (wherein adds
Data for example can be used to generate, update and/or execute one or more characterization models, treatment model and/or other are suitable
Model), and/or can be used in any suitable part of method 100.For example, method 100 may include based on one or
More microbial population data sets are (for example, from the updated micropopulation coefficient that biological sample obtains after user's treatment
According to the updated microbial population feature for concentrating extraction；Deng) more new model (for example, characterization model, treatment model etc.), such as
Based on about microbial population pharmacogenomics spectrum, microbial population composition, microbial population functional diversity and/or other
(for example, related to antibiotic associated disease in terms of suitable microbial population；For example, being based on before treating and microorganism after treatment
Group be data set comparison determine) the adjusting observed more new model.In another embodiment, method 100 may include,
It responds more new model, based on updated model, determines user related with antibiotic associated disease (for example, being not based on more
New the second user associated with biological sample) update (for example, to characterization, to treatment etc.).In another embodiment
In, method 100 may include: to receive biological sample after treatment (for example, after promoting treatment) from user；After treatment
Biological sample (for example, based on the updated microbial population feature that biological sample obtains after treatment, wherein microbial population
Feature can be used together to characterization model) generate the treatment of relevant with antibiotic associated disease user after characterize；Table
Levy based on the antibiotic associated disease characterized after treatment adjusting (for example, for user, one kind for the second user or
Feature etc. before more kinds of treatments)；And/or updated treatment is promoted to user based on updated characterization.However, based on controlling
Biological sample and/or updated microbial population data set after treatment, can carry out method 100 in any suitable manner
Any suitable part and/or any suitable operation.(for example, passing through during the therapeutic process promoted by treatment model
During the entire course for the treatment of the biological sample by reception and analysis from subject, by receive during the entire course for the treatment of come
The data obtained from the investigation of subject) it monitors subject therefore can be used for being generated as being provided by the characterization process of frame S130 every
A feature and the remedy measures of each recommendation provided in frame S140 and S170 generate treatment-validity model.
In frame S180, subject can be prompted in one or more material time points for the therapeutic scheme for being incorporated to treatment
Other biological sample is provided, and can handle and analyze other biological sample (for example, to be similar to about frame S120 institute
The mode of description) generate the microbial population of characterization subject in groups into, functional character and/or pharmacogenomics feature
The measurement of adjusting.For example, being related to following one or more measurement: in earlier time point in the microbial population of subject
The variation of the relative abundance of one or more sorting groups shown, the expression of the specific classification group of the microbial population of subject
Variation, subject microbial group system bacterium the first sorting group abundance and the second sorting group the ratio between abundance, subject
Microbial population in one or more function sections relative abundance variation and any other suitable measure
For being tied to form by micropopulation, the variation of functional character and/or pharmacogenomics feature evaluate therapeutic effect.In addition it or can replace
Dai Di, can be used data that the investigation from subject obtains (with subject to receive experience when treating related) (for example,
The side effect of experience, improved personal evaluation etc.) carry out the validity for the treatment of in determination block S180.However, it is possible to any conjunction
Suitable mode executes the monitoring validity based on one or more treatment, and/or the implementation procedure of the validity based on execution.
The system of method 100 and/or embodiment is at least partly presented as and/or is embodied as being configured as receiving depositing
Store up the machine of the computer-readable medium of computer-readable instruction.These instruction can by with application, small routine, host, service
Device, network, website, communication service, communication interface, patient computer or mobile device hardware/firmware/software element or its
The computer what suitable combination etc. assembles can be performed component and execute.Other system and method for embodiment can at least portion
Ground is divided to be presented as and/or be implemented as being configured as receiving the machine of the computer-readable medium of storage computer-readable instruction.
These instructions can by equipment and collection of network with the above-mentioned type at computer component can be performed execute.It is computer-readable
Medium can be stored in such as RAM, ROM, flash memory, EEPROM, optical device (CD or DVD), hard disk drive, disk drive
On any suitable computer-readable medium of device or any suitable equipment.Component, which can be performed, in computer can be processor, but
It is that any suitable special hardware can (alternatively or additionally) execute instruction.
These figures are illustrated according to preferred embodiment, representative configuration and its modification, system, method and computer journey
Structure, the function and operation of the possible realization of sequence product.In this regard, each frame in flowchart or block diagram can be with table
Show module, section, step or partial code comprising for realizing one or more executable fingers of specified logic function
It enables.It shall also be noted that in some alternative embodiments, the function of referring in frame can not be sent out according to the sequence pointed out in figure
It is raw.For example, be based on related function, two frames continuously shown can actually substantially simultaneously execute or frame sometimes
It can execute in reverse order.Will additionally note that, block diagram and or flow chart illustrate in each frame and block diagram and/or stream
The combination of frame in journey figure can be hard by the system based on dedicated purpose hardware or dedicated purpose that execute specified function or movement
The combination of part and computer instruction is implemented.Embodiment include various system components and various method processes each combination and
Displacement, including any modification, embodiment and specific embodiment.As those skilled in the art by from previous detailed description and from
It recognizes, can modify to embodiment of the present invention and changes without departing from such as appended power in drawings and claims
The scope of the present invention limited in benefit requirement.
Claims (22)
1. it is a kind of for assessing the system that antibiotic can treat illness for user, the system comprises:
Processing system, the processing system can be operated to collect the container containing the biological substance gathered from user,
The processing system includes sequencing system, and the sequencing system can be operated to determine the microorganism sequence from the biological substance
Column；
Microbial population characterizes system, microbial population characterization system can operate with:
Based on the microorganism sequence determine microbial population pharmacogenomics data and microbial population composition data and
At least one of microbial population functional diversity data,
The relevant supplementary data of illness can be treated to the antibiotic that the user gathers by collecting, and
By the supplementary data and from microbial population pharmacogenomics data and the microbial population composition data
Disease can be treated with the antibiotic by being converted to at least one of microbial population functional diversity data extracted feature
The relevant characterization model of disease；And
Treatment system, the treatment system can operate with:
Based on using the characterization model of illness can be treated for above-mentioned antibiotic user's biomaterial is characterized,
Promote the treatment that illness can be treated to the antibiotic of the user.
2. system described in claim 1, wherein the processing system can operate with based on using be directed to and the antibiotic
Nucleic acid material of the primer amplification from the biomaterial of the relevant nucleic acid sequence of illness can be treated, with the determination microorganism
Sequence.
3. system described in claim 1, wherein the processing system can be operated to collect and contain user's biology material
User's container of material, wherein the treatment system can be operated based on the characterization to the user's biomaterial sampled
Promote the treatment, and wherein, the treatment can operate with adjust user microbial population form it is described to improve
Antibiotic can treat the state of illness.
4. system described in claim 1, wherein the feature includes for that can treat the relevant grouping sheet of illness to antibiotic
Position, microbial population relevant at least one of codon mutation, Exon deletion, substitution, gene rearrangement and transposition
Pharmacogenomics feature.
5. system as claimed in claim 4, wherein the microbial population pharmacogenomics feature can dash forward with microbial strains
Denaturation, that microbial strains rely on to microbial strains the resistance of antibiotic at least one of sexual behaviour altogether is related.
6. system as claimed in claim 4, wherein the microbial population pharmacogenomics feature be directed to the antibiotic
The relative abundance that the microbial medicine genomics marker of illness can be treated is related.
7. system described in claim 1, wherein the feature include in resistance and metabolism with bioactive molecule at least
At least one of a kind of relevant nucleotide relative functional features, including following item: structure RNA, adjust RNA, mRNA,
Protein and peptide.
8. system described in claim 1, wherein it includes in urinary tract infections and sexually transmitted disease that the antibiotic, which can treat illness,
At least one, and wherein, the microbial population characterization system can be operated by the supplementary data and from described
In microbial population pharmacogenomics data and microbial population composition data and microbial population functional diversity data
At least one extracted feature is converted to the characterization model at least one of the urinary tract infections and sexually transmitted disease.
9. system according to any one of claims 8, wherein it includes stranguria syndrome associated disease that the antibiotic, which can treat illness, and wherein,
The feature include from the microbial population pharmacogenomics data extract and it is relevant to chimeric penA allele
Microbial population pharmacogenomics feature.
10. system as claimed in claim 9, wherein the treatment system can be operated based on the microbial population drug
The curative effect of genomics feature evaluation cephalosporin treatment, wherein the treatment system can be operated to be promoted based on the curative effect
Into the treatment.
11. system described in claim 1, the system further comprises interface, and the interface can be operated with improvement and institute
State antibiotic can treat the related and user's microbial population pharmacogenomics spectrum based on the user of illness relative to
The comparison of the user group of shared Demographics and the display of antibiotic-related information obtained.
12. a kind of for assessing the method for being directed to the antibiotic associated disease of the first user, which comprises
Microbial population pharmacogenomics are determined based on the obtained microorganism sequence of biological sample gathered from subject
Data；
It receives and the supplementary data set of the antibiotic associated disease information of subject's set is provided；
The first microbial population medicine is determined based on the microbial population pharmacogenomics data and the supplementary data set
Object genomics feature set；
It is generated based on the first microbial population pharmacogenomics feature set related with the antibiotic associated disease
Characterization model；
It is determined based on the characterization model and is related to the characterization of the first user of antibiotic associated disease；With
Promote the treatment to first user based on the characterization, wherein the treatment and the antibiotic related diseases
Disease is related.
13. method described in claim 12, wherein determine that the microbial population pharmacogenomics data include:
The microorganism sequence is determined based on nucleic acid material of the amplification from the biological sample；
Determine the comparison of the microorganism sequence with the reference nucleic acid sequence set about antibiotic associated disease；With
The microbial population pharmacogenomics data are determined based on the comparison.
14. method described in claim 13, wherein expanding the nucleic acid material includes the bridge amplification with next-generation microarray dataset
Substrate and the nucleic acid material carry out multiplex amplification, and wherein it is determined that the microbial population pharmacogenomics data packet
Including can operate with the determination microbial population drug gene in the computing system that communicate with the next-generation microarray dataset
Group learns data.
15. method described in claim 12, the method further includes obtaining and the first microbial population drug base
Because group learning the relevant microbial population drug of relevance between feature set and the antibiotic curative effect for being related to antibiotic associated disease
Genomics feature selecting rule, wherein determine that the first microbial population pharmacogenomics feature set includes based on needle
Microbial population pharmacogenomics data described in the microbial population pharmacogenomics feature selecting rule evaluation are come
Determine the first microbial population pharmacogenomics feature set.
16. method described in claim 12, wherein the first microbial population pharmacogenomics feature set includes and life
The relevant nucleotide relative functional features of at least one of the resistance of object bioactive molecule and metabolism.
17. method described in claim 12, wherein the treatment can be operated to be conducive to micro- life of first user
Object group is the change of pharmacogenomics spectrum, the method further includes:
Biological sample after treatment of the reception from first user；
Updated microbial population pharmacogenomics feature set is determined based on biological sample after the treatment；
Based on the characterization model and updated microbial population pharmacogenomics feature set, determination is related to antibiotic phase
Close the updated characterization of first user of illness；With
Promote the to first user first updated treatment based on the updated characterization.
18. method described in claim 17, the method further includes:
Updated characterization based on first user generates updated antibiotic treatment model；With
Promote the antibiotic treatment to the second user based on the updated antibiotic treatment model, described second through more
New treatment can be operated to adjust the microbial population of second user and form.
19. method of claim 18, the method further includes: institute is determined based on the biological sample of the second user
State the second microbial population pharmacogenomics feature set of the second user, wherein control based on the updated antibiotic
Treating model to promote the antibiotic treatment includes being based on handling the second microbial population drug gene using decision-tree model
Group learns feature set and determines the antibiotic treatment.
20. method described in claim 12,
Wherein, generating the characterization model includes that the characterization model is generated based on microbial population feature set, above-mentioned micro-
Biotic formation feature set contains the first microbial population pharmacogenomics feature set and microbial population Diversity
At least one of feature and microbial population functional diversity feature, and
Wherein it is determined that the characterization of first user includes determining described first based on user's microbial population feature set
The characterization of user, user's microbial population feature set contain user's microbial population pharmacogenomics feature and
At least one of user's microbial population group ingredient Biodiversity Characteristics and user's microbial population functional diversity feature.
21. method of claim 20, wherein the antibiotic associated disease includes stranguria syndrome associated disease, wherein described
Microbial population Diversity Characteristics include the composition characteristic of taxonomical unit related with stranguria syndrome associated disease, and wherein,
The first microbial population pharmacogenomics feature set includes the point mutation feature set of gene relevant to taxonomical unit.
22. method described in claim 21, wherein the gyrA gene of the point mutation feature set and the taxonomical unit and
Point mutation at least one of parC gene is related.
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| PCT/US2017/042015 WO2018013865A1 (en) | 2016-07-13 | 2017-07-13 | Method and system for microbial pharmacogenomics |
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| CN112004943A (en) * | 2017-12-04 | 2020-11-27 | 赛百乐微生物有限公司 | Methods and compositions for identifying and modulating microbiome biochemical pathways to alter phenotypes |
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| CA3030792A1 (en) | 2018-01-18 |
| CO2019001319A2 (en) | 2019-02-19 |
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| EP3484348A1 (en) | 2019-05-22 |
| AU2017295861A1 (en) | 2019-01-24 |
| JP2019521706A (en) | 2019-08-08 |
| JP2022079646A (en) | 2022-05-26 |
| KR102397683B1 (en) | 2022-05-13 |
| CN109475305B (en) | 2022-01-25 |
| WO2018013865A1 (en) | 2018-01-18 |
| SG11201900253TA (en) | 2019-02-27 |
| EA201990294A1 (en) | 2019-08-30 |
| KR20190033561A (en) | 2019-03-29 |
| BR112019000709A2 (en) | 2019-05-14 |
| EP3484348A4 (en) | 2021-11-24 |
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