{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T11:46:48Z","timestamp":1742644008242,"version":"3.37.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U41 HG003751"],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,28]]},"abstract":"Abstract<\/jats:title>\n \n Abstract<\/jats:title>\n Reactome is a database of human biological pathways manually curated from the primary literature and peer-reviewed by experts. To evaluate the utility of Reactome pathways for predicting functional consequences of genetic perturbations, we compared predictions of perturbation effects based on Reactome pathways against published empirical observations. Ten cancer-relevant Reactome pathways, representing diverse biological processes such as signal transduction, cell division, DNA repair and transcriptional regulation, were selected for testing. For each pathway, root input nodes and key pathway outputs were defined. We then used pathway-diagram-derived logic graphs to predict, either by inspection by biocurators or using a novel algorithm MP-BioPath, the effects of bidirectional perturbations (upregulation\/activation or downregulation\/inhibition) of single root inputs on the status of key outputs. These predictions were then compared to published empirical tests. In total, 4968 test cases were analyzed across 10 pathways, of which 847 were supported by published empirical findings. Out of the 847 test cases, curators\u2019 predictions agreed with the experimental evidence in 670 and disagreed in 177 cases, resulting in \u223c81% overall accuracy. MP-BioPath predictions agreed with experimental evidence for 625 and disagreed for 222 test cases, resulting in \u223c75% overall accuracy. The expected accuracy of random guessing was 33%. Per-pathway accuracy did not correlate with the number of pathway edges nor the number of pathway nodes but varied across pathways, ranging from 56% (curator)\/44% (MP-BioPath) for \u2018Mitotic G1 phase and G1\/S transition\u2019 to 100% (curator)\/94% (MP-BioPath) for \u2018RAF\/MAP kinase cascade\u2019. This study highlights the potential of pathway databases such as Reactome in modeling genetic perturbations, promoting standardization of experimental pathway activity readout and supporting hypothesis-driven research by revealing relationships between pathway inputs and outputs that have not yet been directly experimentally tested.<\/jats:p>\n <\/jats:sec>\n \n Database URL<\/jats:title>\n www.reactome.org<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/database\/baac009","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T20:15:11Z","timestamp":1644956111000},"source":"Crossref","is-referenced-by-count":5,"title":["Evaluating the predictive accuracy of curated biological pathways in a public knowledgebase"],"prefix":"10.1093","volume":"2022","author":[{"given":"Adam J","family":"Wright","sequence":"first","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Marija","family":"Orlic-Milacic","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Karen","family":"Rothfels","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Joel","family":"Weiser","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Quang M","family":"Trinh","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Bijay","family":"Jassal","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Robin A","family":"Haw","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"}]},{"given":"Lincoln D","family":"Stein","sequence":"additional","affiliation":[{"name":"Adaptive Oncology Program, Ontario Institute for Cancer Research, 661 University Avenue Suite 500, Toronto, ON M5G 0A3, Canada"},{"name":"Department of Molecular Genetics, University of Toronto, Room 4396, Medical Sciences Building, 1 King\u2019s College Circle, Toronto, ON M5S 1A1, Canada"}]}],"member":"286","published-online":{"date-parts":[[2022,3,6]]},"reference":[{"key":"2022032914355827700_R1","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022032914355827700_R2","doi-asserted-by":"crossref","first-page":"D428","DOI":"10.1093\/nar\/gki072","article-title":"Reactome: a knowledgebase of biological pathways","volume":"33","author":"Joshi-Tope","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2022032914355827700_R3","doi-asserted-by":"crossref","first-page":"D619","DOI":"10.1093\/nar\/gkn863","article-title":"Reactome knowledgebase of human biological pathways and processes","volume":"37","author":"Matthews","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2022032914355827700_R4","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nmeth.3963","article-title":"Impact of outdated gene annotations on pathway enrichment analysis","volume":"13","author":"Wadi","year":"2016","journal-title":"Nat. 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