{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:18:29Z","timestamp":1787995109997,"version":"build-2784847793"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1024,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: Prior biological knowledge greatly facilitates the meaningful interpretation of gene-expression data. Causal networks constructed from individual relationships curated from the literature are particularly suited for this task, since they create mechanistic hypotheses that explain the expression changes observed in datasets.<\/jats:p>\n                  <jats:p>Results: We present and discuss a suite of algorithms and tools for inferring and scoring regulator networks upstream of gene-expression data based on a large-scale causal network derived from the Ingenuity Knowledge Base. We extend the method to predict downstream effects on biological functions and diseases and demonstrate the validity of our approach by applying it to example datasets.<\/jats:p>\n                  <jats:p>Availability: The causal analytics tools \u2018Upstream Regulator Analysis', \u2018Mechanistic Networks', \u2018Causal Network Analysis' and \u2018Downstream Effects Analysis' are implemented and available within Ingenuity Pathway Analysis (IPA, http:\/\/www.ingenuity.com).<\/jats:p>\n                  <jats:p>Supplementary information: \u00a0Supplementary material is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt703","type":"journal-article","created":{"date-parts":[[2013,12,14]],"date-time":"2013-12-14T20:09:42Z","timestamp":1387051782000},"page":"523-530","source":"Crossref","is-referenced-by-count":5394,"title":["Causal analysis approaches in Ingenuity Pathway Analysis"],"prefix":"10.1093","volume":"30","author":[{"given":"Andreas","family":"Kr\u00e4mer","sequence":"first","affiliation":[{"name":"1 Ingenuity Systems, 1700 Seaport Boulevard, Redwood City, CA and 2Translational and Experimental Medicine\u2014Bioinformatics, Sanofi-Aventis, 270 Albany Street, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Green","sequence":"additional","affiliation":[{"name":"1 Ingenuity Systems, 1700 Seaport Boulevard, Redwood City, CA and 2Translational and Experimental Medicine\u2014Bioinformatics, Sanofi-Aventis, 270 Albany Street, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Jack","family":"Pollard","sequence":"additional","affiliation":[{"name":"1 Ingenuity Systems, 1700 Seaport Boulevard, Redwood City, CA and 2Translational and Experimental Medicine\u2014Bioinformatics, Sanofi-Aventis, 270 Albany Street, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Tugendreich","sequence":"additional","affiliation":[{"name":"1 Ingenuity Systems, 1700 Seaport Boulevard, Redwood City, CA and 2Translational and Experimental Medicine\u2014Bioinformatics, Sanofi-Aventis, 270 Albany Street, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,13]]},"reference":[{"key":"2023012710430574400_btt703-B1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/1471-2105-10-275","article-title":"Comparative study of gene set enrichment methods","volume":"10","author":"Abatangelo","year":"2009","journal-title":"BMC Bioinform."},{"key":"2023012710430574400_btt703-B2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ccr.2013.02.014","article-title":"The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia","volume":"3","author":"Arteaga","year":"2013","journal-title":"Cancer cell"},{"key":"2023012710430574400_btt703-B3","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/bioinformatics\/bts090","article-title":"Causal reasoning on biological networks: interpreting transcriptional changes","volume":"28","author":"Chindelevitch","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012710430574400_btt703-B4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2105-13-35","article-title":"Assessing statistical significance in causal graphs","volume":"13","author":"Chindelevitch","year":"2012","journal-title":"BMC Bioinform."},{"key":"2023012710430574400_btt703-B5","first-page":"17","article-title":"Predictive systems biology approach to broad-spectrum, host-directed drug target discovery in infectious diseases","volume":"2013","author":"Felciano","year":"2013","journal-title":"Pac. 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