Full Professor of Computational Biology/Bioinformatics, University of Bologna Italy My main expertise: Genome functional annotation and Machine learning
The \u201cBiBi \u2013 Biodiversity and Bioinformatics\u201d project (University of Bologna Strate... more The \u201cBiBi \u2013 Biodiversity and Bioinformatics\u201d project (University of Bologna Strategic Projects) was aimed to collect and organize molecular anthropology samples and data. One of the specific goals was \u201cthe design, the implementation, the test and maintenance of a data base useful for theoretical studies\u201d. To that end we developed HaPlone, a web-based application built on top of the state-of-the-art Plone (http://plone.org) content management system. The application allows to store, inspect, search and retrieve data through the familiar interface of a standard web browser. Data are stored in the "Subject" data structure, containing both personal and molecular data, that can be inserted, inspected and edited using a user-friendly interface. For each subject, the application calculates on-the-fly the haplogroup, based on its tested UEPs, as well as the most recent common ancestor for each sexual lineage, based on the stored population. The system also takes care of checking data consistency and flags the user for potential errors, such as inconsistent or conflicting UEPs or out-of-range STRs within a given subject. Population subsets can be easily selected (by location, haplogroup, sex, MRCA) using simple query forms, whose reports also provide basic statistics and charts on the selected sets. Furthermore selected subject data can be readily exported to CSV files for processing by other applications such as spreadsheets or statistical packages. By leveraging on Plone access-control features, the application can handle selective access to stored data, allowing fine-grained control on what it can be accessed by an anonymous vs an authenticated user, so it can be used both for internal information sharing and data dissemination simultaneously. Currently the prototype handles only Y-chromosome molecular data (UEPs and STRs), but work is planned to extend data handling to mtDNA data too
MotivationCoiled-coil domains (CCD) are widespread in all organisms performing several crucial fu... more MotivationCoiled-coil domains (CCD) are widespread in all organisms performing several crucial functions. Given their relevance, the computational detection of coiled-coil domains is very important for protein functional annotation. State-of-the art prediction methods include the precise identification of coiled-coil domain boundaries, the annotation of the typical heptad repeat pattern along the coiled-coil helices as well as the prediction of the oligomerization state.ResultsIn this paper we describe CoCoNat, a novel method for predicting coiled-coil helix boundaries, residue-level register annotation and oligomerization state. Our method encodes sequences with the combination of two state-of-the-art protein language models and implements a three-step deep learning procedure concatenated with a Grammatical-Restrained Hidden Conditional Random Field (GRHCRF) for CCD identification and refinement. A final neural network (NN) predicts the oligomerization state. When tested on a blind...
Encyclopedia of Bioinformatics and Computational Biology
Transmembrane proteins constitute some 20%–30% of proteins of all prokaryotic and eukaryotic orga... more Transmembrane proteins constitute some 20%–30% of proteins of all prokaryotic and eukaryotic organisms and are involved in fundamental biological processes. Experimental determination of their structure is difficult due to their peculiar property of being stable in a complex environment consisting of separate hydrophilic and hydrophobic phases. Computational tools are then necessary to fill the gap between the knowledge of protein sequence and the characterization of its role in the context of biological complexity.
Flowchart describing schematic representation of the implemented research approach detailing step... more Flowchart describing schematic representation of the implemented research approach detailing steps for NCWS sample selection and applied population genetics analytical workflow. (PDF 24Â kb)
Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune sys... more Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune system towards substances known as allergens. Apple and hazelnut allergens have been identified in pollens or fruits. Apple allergies are due to four different classes of allergens (Mal d 1, 2, 3, 4), whose allergenicity is related both to genotype and tissue specificity. Building by Homology technique was applied to predict the 3D structures of Mal d 1-4. Starting from the comparison of these results leading to understand the different ways of reactions of the Malds, we have studied the answer of sensitised individuals to 11 apple genotypes, separating fruits skin positive answers from those to the pulp through Skin Prick Test and prick-to-prick test, evidencing different allergic responses to the different cultivar. Climate changes resulting from increases in temperature and air pollution influence pollen allergenicity, responsible for the dramatic raise in respiratory allergies (hay fever, bronchial asthma, conjunctivitis). Although the link between climate change and pollen allergenicity is proven, the underlying mechanism is little understood. Transglutaminases (TGases), a class of enzymes able to post-translationally modify proteins, are activated under stress and involved in some inflammatory responses, enhancing the activity of pro-inflammatory phospholipase A2, suggesting a role in allergies. Aero allergenic (hazelnut. Corylus avellana) and enthomophylus (apple. Malus domestica) pollen exposed to climate changes (different temperatures, relative humidity (rH), acid rain at pH 5.6 and copper pollution (3.10 \ub5g/l)) showed an increase in pollen surface TGase activity in Corylus, while Malus pollen TGase was not significantly affected. Several pollen proteins were post-translationally modified, including the activation of mammalian sPLA2, thus potentially altering pollen allergenicity and inflammation. Western blotting of pollen TGase revealed its induced expression after exposure to stressors, while detection of in situ TGase activity and morphological examination indicated pollen damage and release of TGase. Grants:Crossallergenicity Progetto Strategico d\u2019Ateneo E.F. 2006,University of Bologn
A dramatic increase in prevalence and severity of respiratory allergic diseases in recent years (... more A dramatic increase in prevalence and severity of respiratory allergic diseases in recent years (hay fever, bronchial asthma, seasonal allergic conjunctivitis) is reported by several authors, among which Cecchi et al., 2010. Human activities are resulting in changes in global climate, which in turn have a negative impact on human health. An important example is provided by the influence of climate changes on respiratory diseases triggered by biological aerosol carrying antigenic proteins such as those of pollen grains. Pollen allergenicity is frequently used to study the interrelationship between air pollution and respiratory allergy. Although the link between climate change and/or pollution and increasing allergenic potential of pollen is proven, the underlying mechanism is little understood. Apple (Malus) fruit allergies are mainly due to four different classes of allergens: Mal d 1, 2, 3, 4, but little is known on the expression of allergens also in apple pollen, whose allergenicity is poor, perhaps because dispersed by insects. Here we have investigated the presence of Mal d isoallergens also in pollen using a RT-PCR approach both on ungerminated and germinated pollen. In Corylus (hazelnut) fruit various allergens are reported to be responsible for severe allergic food diseases, but in this case, also pollen is well documented as an allergenic source. We used models mimicking climate and pollution conditions to study vitality and germinability of both pollens. In respect to the natural conditions, changes in temperature, humidity and some pollutants, such as acid rains and copper, alone or in combination, have a negative effect on viability and germination of both types pollen, especially Corylus, and morphological observations showed that the pollen grains are damaged. This can cause a release also of allergens. In addition to the data in literature on the effect of climate changes on the production of more pollen and its allergenes, it is possible that the allergene molecule itself could be modified magnifying its peculiar properties. Transglutaminases (TGases), able to post-translationally modify proteins, have been found recently also in pollen (Serafini-Fracassini et al., 2009). These enzymes play a role on the onset of specific pathologies and associated autoimmune inflammatory conditions (Lorand and Graham, 2003). TGase activity is increased following cellular stresses of different origins (Verderio et al., 2005). In mammalian cells, the intracellular tTGase, is rapidly secreted, following cell insult, into the extracellular environment, where it plays a key role in cell survival (Verderio et al., 2005). We reported that pollen TGase, necessary to allow the apple pollen germination, is released in the pollen cell wall and in the extracellular medium where also polyamines are released (Di Sandro et al., 2010). Its role is still under study, but a relationship between extracellular pollen TGase and the modification of pollen allergens, if co-localised, could be hypothesised. Moreover the pollen TGase activity might be affected by stress conditions such as those caused by environmental changes or pollution. We observed that TGase expression as well as its Ca2+-dependent activity in the two different species of pollen increase in a very remarkable way when pollens are exposed to stressful conditions, especially high humidity, mainly in Corylus, which in addition is particularly affected by pollution. Probably, climate change induce an alteration or damage to pollen cell wall that causes the pollen grains to release their content in the medium, including TGase enzyme, as confirmed by the observed TGase immuno-localization and by the in situ activity assay data, in addition to FITC-cadaverine conjugation
The deluge of sequencing data needs curated association of structural and functional features to ... more The deluge of sequencing data needs curated association of structural and functional features to each sequence in the database. Inference of correct annotation is a major problem of sequence analysis. We highlight why it is difficult to solve the annotation task given the little amount of validated information in the database linking sequences, structure and experimental function in the most curated repository of protein sequences. We review state-of-the-art methods currently benchmarked in the Critical Assessment of protein Function Annotation algorithms (CAFA), an experiment designed to provide a large-scale assessment of computational methods dedicated to predicting protein function.
Climate changes resulting from increases in temperature and air pollution influence pollen allerg... more Climate changes resulting from increases in temperature and air pollution influence pollen allergenicity, responsible for the dramatic raise in respiratory allergies. Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune system towards substances known as allergens. Allergic sensibilization can be of food or respiratory origin; many allergens have been identified in pollens or fruits of different plant species and allergic cross-reactivity can occur in a patient reacting to similar allergens from different origins. Although the link between climate change and pollen allergenicity is proven, the underlying mechanism is little understood. Transglutaminases (TGases), enzymes able to post-translationally modify proteins, are activated under stress and involved in some inflammatory responses, enhancing the activity of pro-inflammatory phospholipase A2, (PLA2). A calcium-dependent TGase activity has been identified in the apple pollen cell wall, raising the possibility that TGase may have a role in the modification of allergens and, when pollen arrives in contact with the human mucosa, the enzyme could be responsible in the transamidation of proteins as PLA2. In Europe a great number of people suffers from apple fruit allergy, but little is known on fruit/pollen cross-allergenicity. Apple fruit allergies are mainly due to four different classes of allergens: Mal d 1, 2, 3, 4. Here we have investigated the presence of Mal d allergens also in pollen to clarify its allergenic potential using a RT-PCR approach both on ungerminated and germinated pollen and we show our initial effort on clarification of climate changes effects on the expression of Mal d allergens. This multidisciplinary approach, aimed to establish the scientific basis for future studies on pollen-food cross allergenicity is supported by the grant \u201cCrossallergenicity\u201d Progetto Strategico d\u2019Ateneo E.F. 2006, University of Bologna
Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in... more Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assa...
The \u201cBiBi \u2013 Biodiversity and Bioinformatics\u201d project (University of Bologna Strate... more The \u201cBiBi \u2013 Biodiversity and Bioinformatics\u201d project (University of Bologna Strategic Projects) was aimed to collect and organize molecular anthropology samples and data. One of the specific goals was \u201cthe design, the implementation, the test and maintenance of a data base useful for theoretical studies\u201d. To that end we developed HaPlone, a web-based application built on top of the state-of-the-art Plone (http://plone.org) content management system. The application allows to store, inspect, search and retrieve data through the familiar interface of a standard web browser. Data are stored in the "Subject" data structure, containing both personal and molecular data, that can be inserted, inspected and edited using a user-friendly interface. For each subject, the application calculates on-the-fly the haplogroup, based on its tested UEPs, as well as the most recent common ancestor for each sexual lineage, based on the stored population. The system also takes care of checking data consistency and flags the user for potential errors, such as inconsistent or conflicting UEPs or out-of-range STRs within a given subject. Population subsets can be easily selected (by location, haplogroup, sex, MRCA) using simple query forms, whose reports also provide basic statistics and charts on the selected sets. Furthermore selected subject data can be readily exported to CSV files for processing by other applications such as spreadsheets or statistical packages. By leveraging on Plone access-control features, the application can handle selective access to stored data, allowing fine-grained control on what it can be accessed by an anonymous vs an authenticated user, so it can be used both for internal information sharing and data dissemination simultaneously. Currently the prototype handles only Y-chromosome molecular data (UEPs and STRs), but work is planned to extend data handling to mtDNA data too
MotivationCoiled-coil domains (CCD) are widespread in all organisms performing several crucial fu... more MotivationCoiled-coil domains (CCD) are widespread in all organisms performing several crucial functions. Given their relevance, the computational detection of coiled-coil domains is very important for protein functional annotation. State-of-the art prediction methods include the precise identification of coiled-coil domain boundaries, the annotation of the typical heptad repeat pattern along the coiled-coil helices as well as the prediction of the oligomerization state.ResultsIn this paper we describe CoCoNat, a novel method for predicting coiled-coil helix boundaries, residue-level register annotation and oligomerization state. Our method encodes sequences with the combination of two state-of-the-art protein language models and implements a three-step deep learning procedure concatenated with a Grammatical-Restrained Hidden Conditional Random Field (GRHCRF) for CCD identification and refinement. A final neural network (NN) predicts the oligomerization state. When tested on a blind...
Encyclopedia of Bioinformatics and Computational Biology
Transmembrane proteins constitute some 20%–30% of proteins of all prokaryotic and eukaryotic orga... more Transmembrane proteins constitute some 20%–30% of proteins of all prokaryotic and eukaryotic organisms and are involved in fundamental biological processes. Experimental determination of their structure is difficult due to their peculiar property of being stable in a complex environment consisting of separate hydrophilic and hydrophobic phases. Computational tools are then necessary to fill the gap between the knowledge of protein sequence and the characterization of its role in the context of biological complexity.
Flowchart describing schematic representation of the implemented research approach detailing step... more Flowchart describing schematic representation of the implemented research approach detailing steps for NCWS sample selection and applied population genetics analytical workflow. (PDF 24Â kb)
Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune sys... more Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune system towards substances known as allergens. Apple and hazelnut allergens have been identified in pollens or fruits. Apple allergies are due to four different classes of allergens (Mal d 1, 2, 3, 4), whose allergenicity is related both to genotype and tissue specificity. Building by Homology technique was applied to predict the 3D structures of Mal d 1-4. Starting from the comparison of these results leading to understand the different ways of reactions of the Malds, we have studied the answer of sensitised individuals to 11 apple genotypes, separating fruits skin positive answers from those to the pulp through Skin Prick Test and prick-to-prick test, evidencing different allergic responses to the different cultivar. Climate changes resulting from increases in temperature and air pollution influence pollen allergenicity, responsible for the dramatic raise in respiratory allergies (hay fever, bronchial asthma, conjunctivitis). Although the link between climate change and pollen allergenicity is proven, the underlying mechanism is little understood. Transglutaminases (TGases), a class of enzymes able to post-translationally modify proteins, are activated under stress and involved in some inflammatory responses, enhancing the activity of pro-inflammatory phospholipase A2, suggesting a role in allergies. Aero allergenic (hazelnut. Corylus avellana) and enthomophylus (apple. Malus domestica) pollen exposed to climate changes (different temperatures, relative humidity (rH), acid rain at pH 5.6 and copper pollution (3.10 \ub5g/l)) showed an increase in pollen surface TGase activity in Corylus, while Malus pollen TGase was not significantly affected. Several pollen proteins were post-translationally modified, including the activation of mammalian sPLA2, thus potentially altering pollen allergenicity and inflammation. Western blotting of pollen TGase revealed its induced expression after exposure to stressors, while detection of in situ TGase activity and morphological examination indicated pollen damage and release of TGase. Grants:Crossallergenicity Progetto Strategico d\u2019Ateneo E.F. 2006,University of Bologn
A dramatic increase in prevalence and severity of respiratory allergic diseases in recent years (... more A dramatic increase in prevalence and severity of respiratory allergic diseases in recent years (hay fever, bronchial asthma, seasonal allergic conjunctivitis) is reported by several authors, among which Cecchi et al., 2010. Human activities are resulting in changes in global climate, which in turn have a negative impact on human health. An important example is provided by the influence of climate changes on respiratory diseases triggered by biological aerosol carrying antigenic proteins such as those of pollen grains. Pollen allergenicity is frequently used to study the interrelationship between air pollution and respiratory allergy. Although the link between climate change and/or pollution and increasing allergenic potential of pollen is proven, the underlying mechanism is little understood. Apple (Malus) fruit allergies are mainly due to four different classes of allergens: Mal d 1, 2, 3, 4, but little is known on the expression of allergens also in apple pollen, whose allergenicity is poor, perhaps because dispersed by insects. Here we have investigated the presence of Mal d isoallergens also in pollen using a RT-PCR approach both on ungerminated and germinated pollen. In Corylus (hazelnut) fruit various allergens are reported to be responsible for severe allergic food diseases, but in this case, also pollen is well documented as an allergenic source. We used models mimicking climate and pollution conditions to study vitality and germinability of both pollens. In respect to the natural conditions, changes in temperature, humidity and some pollutants, such as acid rains and copper, alone or in combination, have a negative effect on viability and germination of both types pollen, especially Corylus, and morphological observations showed that the pollen grains are damaged. This can cause a release also of allergens. In addition to the data in literature on the effect of climate changes on the production of more pollen and its allergenes, it is possible that the allergene molecule itself could be modified magnifying its peculiar properties. Transglutaminases (TGases), able to post-translationally modify proteins, have been found recently also in pollen (Serafini-Fracassini et al., 2009). These enzymes play a role on the onset of specific pathologies and associated autoimmune inflammatory conditions (Lorand and Graham, 2003). TGase activity is increased following cellular stresses of different origins (Verderio et al., 2005). In mammalian cells, the intracellular tTGase, is rapidly secreted, following cell insult, into the extracellular environment, where it plays a key role in cell survival (Verderio et al., 2005). We reported that pollen TGase, necessary to allow the apple pollen germination, is released in the pollen cell wall and in the extracellular medium where also polyamines are released (Di Sandro et al., 2010). Its role is still under study, but a relationship between extracellular pollen TGase and the modification of pollen allergens, if co-localised, could be hypothesised. Moreover the pollen TGase activity might be affected by stress conditions such as those caused by environmental changes or pollution. We observed that TGase expression as well as its Ca2+-dependent activity in the two different species of pollen increase in a very remarkable way when pollens are exposed to stressful conditions, especially high humidity, mainly in Corylus, which in addition is particularly affected by pollution. Probably, climate change induce an alteration or damage to pollen cell wall that causes the pollen grains to release their content in the medium, including TGase enzyme, as confirmed by the observed TGase immuno-localization and by the in situ activity assay data, in addition to FITC-cadaverine conjugation
The deluge of sequencing data needs curated association of structural and functional features to ... more The deluge of sequencing data needs curated association of structural and functional features to each sequence in the database. Inference of correct annotation is a major problem of sequence analysis. We highlight why it is difficult to solve the annotation task given the little amount of validated information in the database linking sequences, structure and experimental function in the most curated repository of protein sequences. We review state-of-the-art methods currently benchmarked in the Critical Assessment of protein Function Annotation algorithms (CAFA), an experiment designed to provide a large-scale assessment of computational methods dedicated to predicting protein function.
Climate changes resulting from increases in temperature and air pollution influence pollen allerg... more Climate changes resulting from increases in temperature and air pollution influence pollen allergenicity, responsible for the dramatic raise in respiratory allergies. Allergies are a complex of symptoms derived from altered IgE-mediated reactions of the immune system towards substances known as allergens. Allergic sensibilization can be of food or respiratory origin; many allergens have been identified in pollens or fruits of different plant species and allergic cross-reactivity can occur in a patient reacting to similar allergens from different origins. Although the link between climate change and pollen allergenicity is proven, the underlying mechanism is little understood. Transglutaminases (TGases), enzymes able to post-translationally modify proteins, are activated under stress and involved in some inflammatory responses, enhancing the activity of pro-inflammatory phospholipase A2, (PLA2). A calcium-dependent TGase activity has been identified in the apple pollen cell wall, raising the possibility that TGase may have a role in the modification of allergens and, when pollen arrives in contact with the human mucosa, the enzyme could be responsible in the transamidation of proteins as PLA2. In Europe a great number of people suffers from apple fruit allergy, but little is known on fruit/pollen cross-allergenicity. Apple fruit allergies are mainly due to four different classes of allergens: Mal d 1, 2, 3, 4. Here we have investigated the presence of Mal d allergens also in pollen to clarify its allergenic potential using a RT-PCR approach both on ungerminated and germinated pollen and we show our initial effort on clarification of climate changes effects on the expression of Mal d allergens. This multidisciplinary approach, aimed to establish the scientific basis for future studies on pollen-food cross allergenicity is supported by the grant \u201cCrossallergenicity\u201d Progetto Strategico d\u2019Ateneo E.F. 2006, University of Bologna
Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in... more Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assa...
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Papers by rita casadio