Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.

<h4>Background</h4>Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and...

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Autores principales:	Ramesh Menon, Cinthia Farina
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d391feb185643f185cc4d2f6b40d04f
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spelling	oai:doaj.org-article:3d391feb185643f185cc4d2f6b40d04f2021-11-18T06:55:24ZShared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.1932-620310.1371/journal.pone.0018660https://doaj.org/article/3d391feb185643f185cc4d2f6b40d04f2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21533026/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes.<h4>Methodology/principal findings</h4>We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D) by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz.<h4>Conclusions/significance</h4>The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.Ramesh MenonCinthia FarinaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18660 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ramesh Menon Cinthia Farina Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
description	<h4>Background</h4>Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes.<h4>Methodology/principal findings</h4>We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D) by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz.<h4>Conclusions/significance</h4>The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.
format	article
author	Ramesh Menon Cinthia Farina
author_facet	Ramesh Menon Cinthia Farina
author_sort	Ramesh Menon
title	Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
title_short	Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
title_full	Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
title_fullStr	Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
title_full_unstemmed	Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
title_sort	shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3d391feb185643f185cc4d2f6b40d04f
work_keys_str_mv	AT rameshmenon sharedmolecularandfunctionalframeworksamongfivecomplexhumandisordersacomparativestudyoninteractomeslinkedtosusceptibilitygenes AT cinthiafarina sharedmolecularandfunctionalframeworksamongfivecomplexhumandisordersacomparativestudyoninteractomeslinkedtosusceptibilitygenes
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Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.

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