The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species

Creators: Shefchek, Kent A.; Grove, Chris

Abstract

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven't been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics.

Additional Information

© 2019 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received September 20, 2019; Revised October 09, 2019; Editorial Decision October 10, 2019; Accepted October 14, 2019, Published: 08 November 2019. Data Availability: The Monarch platform is comprised of multiple components: user interface, data, ontologies, software tools and algorithms. The underlying data are derived from multiple external sources, the use and secondary use of which is governed by the corresponding original license for each source; as we have described in detail, this is not without complex implications (50). It is therefore not possible to provide everything under a unified license. Our integrated data corpus is available for bulk download as RDF formatted files, with subsets of this data as tab-separated value files (https://archive.monarchinitiative.org/latest). Our Neo4j database and Solr index are also publicly available in this archive. Our API provides programmatic access to associations of individual entities. General information about entities, such as definitions, synonyms and cross references, is also available at https://api.monarchinitiative.org/api. A glossary of terms and abbreviations used in this manuscript can be found at https://beta.monarchinitiative.org/glossary. We would like to thank the many people who have contributed to the improvements and updates we have reported here, including (but not limited to) Donna Maglott, Anne Pariser and Janine Lewis. Funding: National Institutes of Health (NIH) Office of the Director (OD); The Monarch Initiative [1R24OD011883]; Forums for Integrative Phenomics [1U13CA221044]; Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231 to S.C., N.L.H., N.D., M.J., S.E.L., C.J.M., J.R., D.U]; EMBL-EBI Core Funds, Open Targets [OTAR005]; European Union's Horizon 2020 Research and Innovation Programme [654248 (CORBEL),676559 (ELIXIR Excelerate) to S.J., P.R., Z.M.P.]; National Human Genome Research Institute at the US National Institutes of Health [U24 HG002223 to C.G.]; UK Medical Research Council; UK Biotechnology and Biological Sciences Research Council; National Human Genome Research Institute at the US National Institutes of Health [U41HG006627 to A.H.]; Wellcome Trust [104967/Z/14/Z]; National Human Genome Research Institute at the US NIH [U41HG000330 to S.M.B.]; National Human Genome Research Institute (NHGRI) at the US NIH [U41 HG002659 to Y.M.B.]. Funding for open access charge: NIH OD; The Monarch Initiative [1R24OD011883]; Forums for Integrative Phenomics [1U13CA221044]. Conflict of interest statement. None declared.

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