When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases
| العنوان: | When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases |
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| المؤلفون: | Chantal Combe, Vincent Navratil, Vincent Lotteau, Benoît de Chassey |
| المساهمون: | Rétrovirus et Pathologie Comparée, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université de Lyon (COMUE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, U851, Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), INRA, INSERM, FUI, ProdInra, Migration |
| المصدر: | BMC Systems Biology BMC Systems Biology, BioMed Central, 2011, 5, ⟨10.1186/1752-0509-5-13⟩ BMC Systems Biology (5), . (2011) BMC Systems Biology, Vol 5, Iss 1, p 13 (2011) |
| بيانات النشر: | HAL CCSD, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Candidate gene, Proteome, Systems biology, In silico, [SDV]Life Sciences [q-bio], BETA, Hepacivirus, Biology, Communicable Diseases, FUNCTIONAL GENOMIC SCREEN, VIRUS-REPLICATION, GENE-EXPRESSION, TRANSGENIC MICE, V-PROTEINS, TYPE-1, IFIH1, ASSOCIATION, MECHANISMS, Host-Parasite Interactions, 03 medical and health sciences, 0302 clinical medicine, Human interactome, Structural Biology, Interaction network, Modelling and Simulation, Humans, Molecular Biology, Gene, lcsh:QH301-705.5, 030304 developmental biology, Genetics, 0303 health sciences, Systems Biology, Applied Mathematics, Molecular Sequence Annotation, 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 1, Viral replication, lcsh:Biology (General), Modeling and Simulation, Metabolic Networks and Pathways, 030217 neurology & neurosurgery, Research Article |
| الوصف: | Background Comprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data. Results Here, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus. Conclusions The Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology of human diseases. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1752-0509 |
| DOI: | 10.1186/1752-0509-5-13⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d17201b6cfaa5b9a1acdfa7364b41772 https://hal.inrae.fr/hal-02645872 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d17201b6cfaa5b9a1acdfa7364b41772 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17520509 |
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| DOI: | 10.1186/1752-0509-5-13⟩ |