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To overcome these shortcomings, we developed a Three Stage Integrative Pathway Search (<jats:italic>TIPS<\/jats:italic>\n              <jats:sup>\u00a9<\/jats:sup>) approach to reconstruct context-specific active pathways involved in conferring a specific phenotype, from limited amount of perturbation data. The approach was tested on human liver cells to identify pathways that confer cytotoxicity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This paper presents a systems approach that integrates gene expression and cytotoxicity profiles to identify a network of pathways involved in free fatty acid (FFA) and tumor necrosis factor-\u03b1 (TNF-\u03b1) induced cytotoxicity in human hepatoblastoma cells (HepG2\/C3A). Cytotoxicity relevant genes were first identified and then used to reconstruct a network using Bayesian network (BN) analysis. BN inference was used subsequently to predict the effects of perturbing a gene on the other genes in the network and on the cytotoxicity. These predictions were subsequently confirmed through the published literature and further experiments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The <jats:italic>TIPS<\/jats:italic>\n              <jats:sup>\u00a9<\/jats:sup> approach is able to reconstruct active pathways that confer a particular phenotype by integrating gene expression and phenotypic profiles. A web-based version of <jats:italic>TIPS<\/jats:italic>\n              <jats:sup>\u00a9<\/jats:sup> that performs the analysis described herein can be accessed at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.egr.msu.edu\/tips\" ext-link-type=\"uri\">http:\/\/www.egr.msu.edu\/tips<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-8-202","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T18:13:45Z","timestamp":1181844825000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Three Stage Integrative Pathway Search (TIPS\u00a9) framework to identify toxicity relevant genes and pathways"],"prefix":"10.1186","volume":"8","author":[{"given":"Zheng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shireesh","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheenu","family":"Mittal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuerui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lufang","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,6,14]]},"reference":[{"key":"1574_CR1","doi-asserted-by":"publisher","first-page":"S233","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233","volume":"18 Suppl 1","author":"T Ideker","year":"2002","unstructured":"Ideker T, Ozier O, Schwikowski B, Siegel AF: Discovering regulatory and signalling circuits in molecular interaction networks. 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