The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species.

This article has been accepted for publication inNucleic Acids Research, Volume 45, Issue D1, 4 January 2017, Pages D712–D722. https://doi.org/10.1093/nar/gkw1128 Published by Oxford University Press.The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.National Institutes of Health (NIH) [1R24OD011883]; Wellcome Trust [098051]; NIH Undiagnosed Disease Program [HHSN268201300036C, HHSN268201400093P]; Phenotype RCN [NSF-DEB-0956049]; NCI/Leidos [15x143, BD2K U54HG007990-S2 (Haussler; GA4GH), BD2K PA-15-144-U01 (Kesselman; FaceBase)]; Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy [DE- AC02-05CH11231 to J.N.Y., S.C., S.E.L. and C.J.M.]. Funding for open access charge: NIH [1R24OD011883]

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species.

The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species