title: A chemo-centric view of human health and disease.
abstract: Efforts to compile the phenotypic effects of drugs and environmental chemicals offer the opportunity to adopt a chemo-centric view of human health that does not require detailed mechanistic information. Here we consider thousands of chemicals and analyse the relationship of their structures with adverse and therapeutic responses. Our study includes molecules related to the aetiology of 934 health-threatening conditions and used to treat 835 diseases. We first identify chemical moieties that could be independently associated with each phenotypic effect. Using these fragments, we build accurate predictors for approximately 400 clinical phenotypes, finding many privileged and liable structures. Finally, we connect two diseases if they relate to similar chemical structures. The resulting networks of human conditions are able to predict disease comorbidities, as well as identifying potential drug side effects and opportunities for drug repositioning, and show a remarkable coincidence with clinical observations.
authors.affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Duran-Frigola
authors.affiliation: 1] Biostatistics and Bioinformatics Unit, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain [2] Department of Statistics, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Rossell
authors.affiliation: 1] Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
mesh_terms: D002621:Chemistry; D004194:Disease / Q000209:etiology*; D004358:Drug Therapy; D006262:Health; D006801:Humans; D010641:Phenotype