{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T22:11:00Z","timestamp":1675203060128},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":2578,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene\u2013disease associations with the many complex and overlapping phenotypes of human disease.<\/jats:p>\n               <jats:p>Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering. Placing the known gene\u2013disease associations in the context of this space reveals new patterns that suggest previously unknown functional links between proteins, signaling pathways and disease phenotypes. For example, analysis of telangiectasias (spider vein diseases) reveals a previously unrecognized interplay between the TGF-\u03b2 signaling pathway and pentose phosphate pathway. This interaction may mediate glucose-dependent regulation of TGF-\u03b2 signaling, providing a clue to the known association between angiopathies and diabetes and implying new gene candidates for mutational analysis and drug targeting.<\/jats:p>\n               <jats:p>Contact: \u00a0grishin@chop.swmed.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp538","type":"journal-article","created":{"date-parts":[[2009,9,11]],"date-time":"2009-09-11T00:34:34Z","timestamp":1252629274000},"page":"2891-2896","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways"],"prefix":"10.1093","volume":"25","author":[{"given":"Ruslan I.","family":"Sadreyev","sequence":"first","affiliation":[{"name":"1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA"}]},{"given":"Jamison D.","family":"Feramisco","sequence":"additional","affiliation":[{"name":"1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA"}]},{"given":"Hensin","family":"Tsao","sequence":"additional","affiliation":[{"name":"1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA"}]},{"given":"Nick V.","family":"Grishin","sequence":"additional","affiliation":[{"name":"1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA"},{"name":"1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, 2Department of Dermatology, University of California at San Francisco, San Francisco, CA 94115, 3Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, and 4Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA"}]}],"member":"286","published-online":{"date-parts":[[2009,9,10]]},"reference":[{"key":"2023013112152008600_B1","doi-asserted-by":"crossref","first-page":"D793","DOI":"10.1093\/nar\/gkn665","article-title":"McKusick's Online Mendelian Inheritance in Man (OMIM)","volume":"37","author":"Amberger","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023013112152008600_B2","volume-title":"Biochemistry.","author":"Berg","year":"2001"},{"key":"2023013112152008600_B3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/ng1764","article-title":"Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome","volume":"38","author":"Coucke","year":"2006","journal-title":"Nat. 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