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

Author:

Shefchek Kent A1ORCID,Harris Nomi L2,Gargano Michael3,Matentzoglu Nicolas4,Unni Deepak2,Brush Matthew5,Keith Daniel1,Conlin Tom1,Vasilevsky Nicole5ORCID,Zhang Xingmin Aaron3,Balhoff James P6ORCID,Babb Larry7,Bello Susan M8,Blau Hannah3,Bradford Yvonne9,Carbon Seth2,Carmody Leigh3,Chan Lauren E10,Cipriani Valentina11,Cuzick Alayne12,Della Rocca Maria13,Dunn Nathan2,Essaid Shahim5,Fey Petra14,Grove Chris15,Gourdine Jean-Phillipe5,Hamosh Ada16,Harris Midori17,Helbig Ingo18192021,Hoatlin Maureen22,Joachimiak Marcin2,Jupp Simon4ORCID,Lett Kenneth B1,Lewis Suzanna E2,McNamara Craig23,Pendlington Zoë M4,Pilgrim Clare17,Putman Tim1,Ravanmehr Vida3,Reese Justin2,Riggs Erin24,Robb Sofia25,Roncaglia Paola4,Seager James12,Segerdell Erik26,Similuk Morgan27,Storm Andrea L13,Thaxon Courtney28,Thessen Anne1,Jacobsen Julius O B11,McMurry Julie A10,Groza Tudor23,Köhler Sebastian29ORCID,Smedley Damian11,Robinson Peter N3ORCID,Mungall Christopher J2,Haendel Melissa A15,Munoz-Torres Monica C1ORCID,Osumi-Sutherland David4

Affiliation:

1. Center for Genome Research and Biocomputing, Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA

2. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94710, USA

3. The Jackson Laboratory For Genomic Medicine, Farmington, CT 06032, USA

4. European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK

5. Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA

6. Renaissance Computing Institute at UNC, Chapel Hill, NC 27517, USA

7. Broad Institute, Cambridge, MA 02142, USA

8. The Jackson Laboratory, Bar Harbor, ME 04609, USA

9. Institute of Neuroscience, University of Oregon, Eugene, OR 97401, USA

10. College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331, USA

11. William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK

12. Rothamsted Research, Harpenden AL5 2JQ, UK

13. Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD 20892, USA

14. dictyBase, Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA

15. California Institute of Technology, Pasadena, CA 91125, USA

16. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

17. University of Cambridge, Cambridge CB2 1TN, UK

18. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA

19. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA

20. Department of Neuropediatrics, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany

21. Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA

22. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA

23. Pryzm Health, 4215 Queensland, Australia

24. Autism & Developmental Medicine Institute, Geisinger, Danville, PA 17837, USA

25. Stowers Institute for Medical Research, Kansas City, MO 64110, USA

26. Xenbase, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA

27. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA

28. University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA

29. Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

Abstract

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.

Funder

The Monarch Initiative

Forums for Integrative Phenomics

U.S. Department of Energy

EMBL-EBI

Horizon 2020

National Institutes of Health

Medical Research Council

Biotechnology and Biological Sciences Research Council

Wellcome Trust

Publisher

Oxford University Press (OUP)

Subject

Genetics

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