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

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.

Authors:
ORCiD logo [1];  [2];  [3];  [4];  [2];  [5];  [1];  [1]; ORCiD logo [5];  [3]; ORCiD logo [6];  [7];  [8];  [3];  [9];  [2];  [3];  [10];  [11];  [12] more »;  [13];  [2];  [5];  [14];  [15];  [5];  [16];  [17];  [18];  [19];  [2]; ORCiD logo [4];  [1];  [2];  [20];  [4];  [17];  [1];  [3];  [2];  [21];  [22];  [4];  [12];  [23];  [24];  [13];  [25];  [1];  [11];  [10];  [20]; ORCiD logo [26];  [11]; ORCiD logo [3];  [2];  [27]; ORCiD logo [1];  [4] « less
  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, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA, Department of Neuropediatrics, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany, Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
  19. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA
  20. Pryzm Health, 4215 Queensland, Australia
  21. Autism & Developmental Medicine Institute, Geisinger, Danville, PA 17837, USA
  22. Stowers Institute for Medical Research, Kansas City, MO 64110, USA
  23. Xenbase, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA
  24. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  25. University of North Carolina Medical School, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA
  26. Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
  27. Center for Genome Research and Biocomputing, Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA, Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1573519
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Nucleic Acids Research
Additional Journal Information:
Journal Name: Nucleic Acids Research; Journal ID: ISSN 0305-1048
Publisher:
Oxford University Press
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Shefchek, Kent A., Harris, Nomi L., Gargano, Michael, Matentzoglu, Nicolas, Unni, Deepak, Brush, Matthew, Keith, Daniel, Conlin, Tom, Vasilevsky, Nicole, Zhang, Xingmin Aaron, Balhoff, James P., Babb, Larry, Bello, Susan M., Blau, Hannah, Bradford, Yvonne, Carbon, Seth, Carmody, Leigh, Chan, Lauren E., Cipriani, Valentina, Cuzick, Alayne, Rocca, Maria D., Dunn, Nathan, Essaid, Shahim, Fey, Petra, Grove, Chris, Gourdine, Jean-Phillipe, Hamosh, Ada, Harris, Midori, Helbig, Ingo, Hoatlin, Maureen, Joachimiak, Marcin, Jupp, Simon, Lett, Kenneth B., Lewis, Suzanna E., McNamara, Craig, Pendlington, Zoë M., Pilgrim, Clare, Putman, Tim, Ravanmehr, Vida, Reese, Justin, Riggs, Erin, Robb, Sofia, Roncaglia, Paola, Seager, James, Segerdell, Erik, Similuk, Morgan, Storm, Andrea L., Thaxon, Courtney, Thessen, Anne, Jacobsen, Julius O. B., McMurry, Julie A., Groza, Tudor, Köhler, Sebastian, Smedley, Damian, Robinson, Peter N., Mungall, Christopher J., Haendel, Melissa A., Munoz-Torres, Monica C., and Osumi-Sutherland, David. The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species. United Kingdom: N. p., 2019. Web. doi:10.1093/nar/gkz997.
Shefchek, Kent A., Harris, Nomi L., Gargano, Michael, Matentzoglu, Nicolas, Unni, Deepak, Brush, Matthew, Keith, Daniel, Conlin, Tom, Vasilevsky, Nicole, Zhang, Xingmin Aaron, Balhoff, James P., Babb, Larry, Bello, Susan M., Blau, Hannah, Bradford, Yvonne, Carbon, Seth, Carmody, Leigh, Chan, Lauren E., Cipriani, Valentina, Cuzick, Alayne, Rocca, Maria D., Dunn, Nathan, Essaid, Shahim, Fey, Petra, Grove, Chris, Gourdine, Jean-Phillipe, Hamosh, Ada, Harris, Midori, Helbig, Ingo, Hoatlin, Maureen, Joachimiak, Marcin, Jupp, Simon, Lett, Kenneth B., Lewis, Suzanna E., McNamara, Craig, Pendlington, Zoë M., Pilgrim, Clare, Putman, Tim, Ravanmehr, Vida, Reese, Justin, Riggs, Erin, Robb, Sofia, Roncaglia, Paola, Seager, James, Segerdell, Erik, Similuk, Morgan, Storm, Andrea L., Thaxon, Courtney, Thessen, Anne, Jacobsen, Julius O. B., McMurry, Julie A., Groza, Tudor, Köhler, Sebastian, Smedley, Damian, Robinson, Peter N., Mungall, Christopher J., Haendel, Melissa A., Munoz-Torres, Monica C., & Osumi-Sutherland, David. The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species. United Kingdom. doi:10.1093/nar/gkz997.
Shefchek, Kent A., Harris, Nomi L., Gargano, Michael, Matentzoglu, Nicolas, Unni, Deepak, Brush, Matthew, Keith, Daniel, Conlin, Tom, Vasilevsky, Nicole, Zhang, Xingmin Aaron, Balhoff, James P., Babb, Larry, Bello, Susan M., Blau, Hannah, Bradford, Yvonne, Carbon, Seth, Carmody, Leigh, Chan, Lauren E., Cipriani, Valentina, Cuzick, Alayne, Rocca, Maria D., Dunn, Nathan, Essaid, Shahim, Fey, Petra, Grove, Chris, Gourdine, Jean-Phillipe, Hamosh, Ada, Harris, Midori, Helbig, Ingo, Hoatlin, Maureen, Joachimiak, Marcin, Jupp, Simon, Lett, Kenneth B., Lewis, Suzanna E., McNamara, Craig, Pendlington, Zoë M., Pilgrim, Clare, Putman, Tim, Ravanmehr, Vida, Reese, Justin, Riggs, Erin, Robb, Sofia, Roncaglia, Paola, Seager, James, Segerdell, Erik, Similuk, Morgan, Storm, Andrea L., Thaxon, Courtney, Thessen, Anne, Jacobsen, Julius O. B., McMurry, Julie A., Groza, Tudor, Köhler, Sebastian, Smedley, Damian, Robinson, Peter N., Mungall, Christopher J., Haendel, Melissa A., Munoz-Torres, Monica C., and Osumi-Sutherland, David. Fri . "The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species". United Kingdom. doi:10.1093/nar/gkz997.
@article{osti_1573519,
title = {The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species},
author = {Shefchek, Kent A. and Harris, Nomi L. and Gargano, Michael and Matentzoglu, Nicolas and Unni, Deepak and Brush, Matthew and Keith, Daniel and Conlin, Tom and Vasilevsky, Nicole and Zhang, Xingmin Aaron and Balhoff, James P. and Babb, Larry and Bello, Susan M. and Blau, Hannah and Bradford, Yvonne and Carbon, Seth and Carmody, Leigh and Chan, Lauren E. and Cipriani, Valentina and Cuzick, Alayne and Rocca, Maria D. and Dunn, Nathan and Essaid, Shahim and Fey, Petra and Grove, Chris and Gourdine, Jean-Phillipe and Hamosh, Ada and Harris, Midori and Helbig, Ingo and Hoatlin, Maureen and Joachimiak, Marcin and Jupp, Simon and Lett, Kenneth B. and Lewis, Suzanna E. and McNamara, Craig and Pendlington, Zoë M. and Pilgrim, Clare and Putman, Tim and Ravanmehr, Vida and Reese, Justin and Riggs, Erin and Robb, Sofia and Roncaglia, Paola and Seager, James and Segerdell, Erik and Similuk, Morgan and Storm, Andrea L. and Thaxon, Courtney and Thessen, Anne and Jacobsen, Julius O. B. and McMurry, Julie A. and Groza, Tudor and Köhler, Sebastian and Smedley, Damian and Robinson, Peter N. and Mungall, Christopher J. and Haendel, Melissa A. and Munoz-Torres, Monica C. and Osumi-Sutherland, David},
abstractNote = {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.},
doi = {10.1093/nar/gkz997},
journal = {Nucleic Acids Research},
number = ,
volume = ,
place = {United Kingdom},
year = {2019},
month = {11}
}

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DOI: 10.1093/nar/gkz997

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Works referenced in this record:

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants
journal, February 2019

  • Ji, Jianling; Shen, Lishuang; Bootwalla, Moiz
  • Molecular Case Studies, Vol. 5, Issue 2
  • DOI: 10.1101/mcs.a003756

A Census of Disease Ontologies
journal, July 2018


Uberon, an integrative multi-species anatomy ontology
journal, January 2012

  • Mungall, Christopher J.; Torniai, Carlo; Gkoutos, Georgios V.
  • Genome Biology, Vol. 13, Issue 1
  • DOI: 10.1186/gb-2012-13-1-r5

The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of the mammalian genome that informs conservation
journal, May 2018

  • Muñoz-Fuentes, Violeta; Cacheiro, Pilar; Meehan, Terrence F.
  • Conservation Genetics, Vol. 19, Issue 4
  • DOI: 10.1007/s10592-018-1072-9

The Drosophila phenotype ontology
journal, January 2013

  • Osumi-Sutherland, David; Marygold, Steven J.; Millburn, Gillian H.
  • Journal of Biomedical Semantics, Vol. 4, Issue 1
  • DOI: 10.1186/2041-1480-4-30

Building a livestock genetic and genomic information knowledgebase through integrative developments of Animal QTLdb and CorrDB
journal, November 2018

  • Hu, Zhi-Liang; Park, Carissa A.; Reecy, James M.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1084

The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019
journal, November 2018

  • Buniello, Annalisa; MacArthur, Jacqueline A. L.; Cerezo, Maria
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1120

Plain-language medical vocabulary for precision diagnosis
journal, April 2018

  • Vasilevsky, Nicole A.; Foster, Erin D.; Engelstad, Mark E.
  • Nature Genetics, Vol. 50, Issue 4
  • DOI: 10.1038/s41588-018-0096-x

Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation
journal, November 2009


KEGG: new perspectives on genomes, pathways, diseases and drugs
journal, November 2016

  • Kanehisa, Minoru; Furumichi, Miho; Tanabe, Mao
  • Nucleic Acids Research, Vol. 45, Issue D1
  • DOI: 10.1093/nar/gkw1092

Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research
journal, January 2013


matchbox : An open-source tool for patient matching via the Matchmaker Exchange
journal, October 2018

  • Arachchi, Harindra; Wojcik, Monica H.; Weisburd, Benjamin
  • Human Mutation, Vol. 39, Issue 12
  • DOI: 10.1002/humu.23655

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources
journal, November 2018

  • Köhler, Sebastian; Carmody, Leigh; Vasilevsky, Nicole
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1105

The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease
journal, February 2017

  • Ramoni, Rachel B.; Mulvihill, John J.; Adams, David R.
  • The American Journal of Human Genetics, Vol. 100, Issue 2
  • DOI: 10.1016/j.ajhg.2017.01.006

FlyBase 2.0: the next generation
journal, October 2018

  • Thurmond, Jim; Goodman, Joshua L.; Strelets, Victor B.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1003

Modeling sample variables with an Experimental Factor Ontology
journal, March 2010


The Reactome Pathway Knowledgebase
journal, November 2017

  • Fabregat, Antonio; Jupe, Steven; Matthews, Lisa
  • Nucleic Acids Research, Vol. 46, Issue D1
  • DOI: 10.1093/nar/gkx1132

BgeeDB, an R package for retrieval of curated expression datasets and for gene list expression localization enrichment tests
journal, January 2016


Clinical Practice Guidelines for Rare Diseases: The Orphanet Database
journal, January 2017


The zebrafish anatomy and stage ontologies: representing the anatomy and development of Danio rerio
journal, January 2014

  • Van Slyke, Ceri E.; Bradford, Yvonne M.; Westerfield, Monte
  • Journal of Biomedical Semantics, Vol. 5, Issue 1
  • DOI: 10.1186/2041-1480-5-12

NCI Thesaurus: A semantic model integrating cancer-related clinical and molecular information
journal, February 2007

  • Sioutos, Nicholas; Coronado, Sherri de; Haber, Margaret W.
  • Journal of Biomedical Informatics, Vol. 40, Issue 1
  • DOI: 10.1016/j.jbi.2006.02.013

Dead simple OWL design patterns
journal, June 2017

  • Osumi-Sutherland, David; Courtot, Melanie; Balhoff, James P.
  • Journal of Biomedical Semantics, Vol. 8, Issue 1
  • DOI: 10.1186/s13326-017-0126-0

A specific mutation in TBL1XR1 causes Pierpont syndrome
journal, January 2016


OMIM.org: leveraging knowledge across phenotype–gene relationships
journal, November 2018

  • Amberger, Joanna S.; Bocchini, Carol A.; Scott, Alan F.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1151

STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets
journal, November 2018

  • Szklarczyk, Damian; Gable, Annika L.; Lyon, David
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1131

An analysis and metric of reusable data licensing practices for biomedical resources
journal, March 2019


The Mammalian Phenotype Ontology as a unifying standard for experimental and high-throughput phenotyping data
journal, September 2012


The Comparative Toxicogenomics Database: update 2019
journal, September 2018

  • Davis, Allan Peter; Grondin, Cynthia J.; Johnson, Robin J.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky868

WormBase 2017: molting into a new stage
journal, October 2017

  • Lee, Raymond Y. N.; Howe, Kevin L.; Harris, Todd W.
  • Nucleic Acids Research, Vol. 46, Issue D1
  • DOI: 10.1093/nar/gkx998

The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability
journal, July 2016

  • Diehl, Alexander D.; Meehan, Terrence F.; Bradford, Yvonne M.
  • Journal of Biomedical Semantics, Vol. 7, Issue 1
  • DOI: 10.1186/s13326-016-0088-7

Mouse Genome Database (MGD) 2019
journal, November 2018

  • Bult, Carol J.; Blake, Judith A.; Smith, Cynthia L.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1056

Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome
journal, September 2014

  • Zemojtel, Tomasz; Köhler, Sebastian; Mackenroth, Luisa
  • Science Translational Medicine, Vol. 6, Issue 252
  • DOI: 10.1126/scitranslmed.3009262

Integrating phenotype ontologies across multiple species
journal, January 2010

  • Mungall, Christopher J.; Gkoutos, Georgios V.; Smith, Cynthia L.
  • Genome Biology, Vol. 11, Issue 1
  • DOI: 10.1186/gb-2010-11-1-r2

ClinVar at five years: Delivering on the promise
journal, October 2018

  • Landrum, Melissa J.; Kattman, Brandi L.
  • Human Mutation, Vol. 39, Issue 11
  • DOI: 10.1002/humu.23641

The BioGRID interaction database: 2019 update
journal, November 2018

  • Oughtred, Rose; Stark, Chris; Breitkreutz, Bobby-Joe
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1079

The 100 000 Genomes Project: bringing whole genome sequencing to the NHS
journal, April 2018


Semantic integration of clinical laboratory tests from electronic health records for deep phenotyping and biomarker discovery
journal, May 2019


Next-generation diagnostics and disease-gene discovery with the Exomiser
journal, November 2015

  • Smedley, Damian; Jacobsen, Julius O. B.; Jäger, Marten
  • Nature Protocols, Vol. 10, Issue 12
  • DOI: 10.1038/nprot.2015.124

ClinGen — The Clinical Genome Resource
journal, June 2015

  • Rehm, Heidi L.; Berg, Jonathan S.; Brooks, Lisa D.
  • New England Journal of Medicine, Vol. 372, Issue 23
  • DOI: 10.1056/NEJMsr1406261

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species
journal, November 2016

  • Mungall, Christopher J.; McMurry, Julie A.; Köhler, Sebastian
  • Nucleic Acids Research, Vol. 45, Issue D1
  • DOI: 10.1093/nar/gkw1128

Mouse Phenome Database: an integrative database and analysis suite for curated empirical phenotype data from laboratory mice
journal, November 2017

  • Bogue, Molly A.; Grubb, Stephen C.; Walton, David O.
  • Nucleic Acids Research, Vol. 46, Issue D1
  • DOI: 10.1093/nar/gkx1082