{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:34:15Z","timestamp":1793424855403,"version":"4.5.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,4,6]]},"abstract":"<jats:p>\n                    Biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that\n                    <jats:italic>SOX13<\/jats:italic>\n                    regulates angiogenesis, and that\n                    <jats:italic>SEC23IP<\/jats:italic>\n                    is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks\u2014many predating the plant-animal divergence\u2014capable of identifying candidate disease genes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0910200107","type":"journal-article","created":{"date-parts":[[2010,3,22]],"date-time":"2010-03-22T22:36:27Z","timestamp":1269297387000},"page":"6544-6549","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":270,"title":["Systematic discovery of nonobvious human disease models through orthologous phenotypes"],"prefix":"10.1073","volume":"107","author":[{"given":"Kriston L.","family":"McGary","sequence":"first","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Joo","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"},{"name":"The Howard Hughes Medical Institute and Department of Molecular Cell and Developmental Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O.","family":"Woods","sequence":"additional","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ji","family":"Cha","sequence":"additional","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Wallingford","sequence":"additional","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"},{"name":"The Howard Hughes Medical Institute and Department of Molecular Cell and Developmental Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Marcotte","sequence":"additional","affiliation":[{"name":"Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology,"},{"name":"Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198403013100902"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81722-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450110607011455"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450110607011411"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05557"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/91.1.67"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.01.013"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn665"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl940"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki066"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.69"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150021"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-12-r258"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh113"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.5197"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1644"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142293999"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419890"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00084-06"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-08-0742"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1751"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.435107"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0686"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135344"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.2.469"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07891"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940311200913"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/15507"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(70)90098-9"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1876"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.10.005"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000988"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1534710100"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.2307\/2412448"},{"key":"e_1_3_3_35_2","volume-title":"Lectures on Comparative Anatomy and Physiology of the Invertebrate Animals","author":"Owen R","year":"1843","unstructured":"R Owen Lectures on Comparative Anatomy and Physiology of the Invertebrate Animals (Longmans, Brown, Green and Longmans, London, 1843)."},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.82303","volume-title":"On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life","author":"Darwin C","year":"1859","unstructured":"C Darwin On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life (John Murray, London, 1859)."},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/415757a"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0910200107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:38:17Z","timestamp":1685493497000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0910200107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,22]]},"references-count":37,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2010,4,6]]}},"alternative-id":["10.1073\/pnas.0910200107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0910200107","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.2687956.2454054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.2351054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.14866260","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.793564645","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.2820055","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.11668056","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.2809060","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.2687956.3257054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,22]]},"assertion":[{"value":"2010-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}