{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T23:06:37Z","timestamp":1765667197656,"version":"3.37.3"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:00:00Z","timestamp":1508284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM102365, T32 GM007365 and F30 AI124553"],"award-info":[{"award-number":["R01 GM102365, T32 GM007365 and F30 AI124553"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["IC2014-1387"],"award-info":[{"award-number":["IC2014-1387"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Summary<\/jats:title><jats:p>Gene-based supervised machine learning classification models have been widely used to differentiate disease states, predict disease progression and determine effective treatment options. However, many of these classifiers are sensitive to noise and frequently do not replicate in external validation sets. For complex, heterogeneous diseases, these classifiers are further limited by being unable to capture varying combinations of genes that lead to the same phenotype. Pathway-based classification can overcome these challenges by using robust, aggregate features to represent biological mechanisms. In this work, we developed a novel pathway-based approach, PRObabilistic Pathway Score, which uses genes to calculate individualized pathway scores for classification. Unlike previous individualized pathway-based classification methods that use gene sets, we incorporate gene interactions using probabilistic graphical models to more accurately represent the underlying biology and achieve better performance. We apply our method to differentiate two similar complex diseases, ulcerative colitis (UC) and Crohn\u2019s disease (CD), which are the two main types of inflammatory bowel disease (IBD). Using five IBD datasets, we compare our method against four gene-based and four alternative pathway-based classifiers in distinguishing CD from UC. We demonstrate superior classification performance and provide biological insight into the top pathways separating CD from UC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and Implementation<\/jats:title><jats:p>PROPS is available as a R package, which can be downloaded at http:\/\/simtk.org\/home\/props or on Bioconductor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx651","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T11:10:08Z","timestamp":1508238608000},"page":"985-993","source":"Crossref","is-referenced-by-count":25,"title":["A probabilistic pathway score (PROPS) for classification with applications to inflammatory bowel disease"],"prefix":"10.1093","volume":"34","author":[{"given":"Lichy","family":"Han","sequence":"first","affiliation":[{"name":"Biomedical Informatics Training Program, Stanford University, Stanford, CA, USA"}]},{"given":"Mateusz","family":"Maciejewski","sequence":"additional","affiliation":[{"name":"Inflammation & Immunology, Pfizer Inc., Cambridge, MA, USA"}]},{"given":"Christoph","family":"Brockel","sequence":"additional","affiliation":[{"name":"Hill\u2019s Pet Nutrition, Topeka, KS, USA"}]},{"given":"William","family":"Gordon","sequence":"additional","affiliation":[{"name":"Inflammation & Immunology, Pfizer Inc., Cambridge, MA, USA"}]},{"given":"Scott B","family":"Snapper","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Division of Gastroenterology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}]},{"given":"Joshua R","family":"Korzenik","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}]},{"given":"Lovisa","family":"Afzelius","sequence":"additional","affiliation":[{"name":"Inflammation & Immunology, Pfizer Inc., Cambridge, MA, USA"}]},{"given":"Russ B","family":"Altman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University, Stanford, CA, USA"},{"name":"Department of Bioengineering, Stanford University, Stanford, CA, USA"}]}],"member":"286","published-online":{"date-parts":[[2017,10,18]]},"reference":[{"key":"2023012712570707400_btx651-B1","doi-asserted-by":"crossref","first-page":"CD003715","DOI":"10.1002\/14651858.CD003715.pub2","article-title":"Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease","volume-title":"Cochrane database Syst. 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