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In the last two decades, many studies have identified numerous genes associated with this disease. However, there is no comprehensive research resource for PAH or other PH types that integrates various genetic studies and their related biological information. Thus, the number of associated genes, and their strength of evidence, is unclear. In this study, we tested the hypothesis that a web-based knowledgebase could be used to develop a biological map of highly interrelated, functionally important genes in PAH. We developed the pulmonary arterial hypertension knowledgebase (PAHKB, http:\/\/bioinfo.mc.vanderbilt.edu\/PAHKB\/), a comprehensive database with a user-friendly web interface. PAHKB extracts genetic data from all available sources, including those from association studies, genetic mutation, gene expression, animal model, supporting literature, various genomic annotations, gene networks, cellular and regulatory pathways, as well as microRNAs. Moreover, PAHKB provides online tools for data browsing and searching, data integration, pathway graphical presentation, and gene ranking. In the current release, PAHKB contains 341 human PH-related genes (293 protein coding and 48 non-coding genes) curated from over 1000 PubMed abstracts. Based on the top 39 ranked PAH-related genes in PAHKB, we constructed a core biological map. This core map was enriched with the TGF-beta signaling pathway, focal adhesion, cytokine\u2013cytokine receptor interaction, and MAPK signaling. In addition, the reconstructed map elucidates several novel cancer signaling pathways, which may provide clues to support the application of anti-cancer therapeutics to PAH. In summary, we have developed a system for the identification of core PH-related genes and identified critical signaling pathways that may be relevant to PAH pathogenesis. This system can be easily applied to other pulmonary diseases.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c3mb70496c","type":"journal-article","created":{"date-parts":[[2014,1,10]],"date-time":"2014-01-10T11:54:33Z","timestamp":1389354873000},"page":"732-740","source":"Crossref","is-referenced-by-count":19,"title":["An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis"],"prefix":"10.1093","volume":"10","author":[{"given":"Min","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Vanderbilt University School of Medicine a , Nashville, TN, USA \u00a0 zhongming.zhao@vanderbilt.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University School of Medicine b , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R","family":"Hemnes","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine c , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Loyd","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center d , Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Quantitative Sciences, Vanderbilt University Medical Center g , Nashville, TN, USA"},{"name":"Department of Psychiatry, Vanderbilt University School of Medicine f , Nashville, TN, USA"},{"name":"Department of Cancer Biology, Vanderbilt University School of Medicine e , Nashville, TN, USA"},{"name":"Department of Biomedical Informatics, Vanderbilt University School of Medicine a , Nashville, TN, USA \u00a0 zhongming.zhao@vanderbilt.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,10]]},"reference":[{"key":"2026010815070520900_cit1","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.jacc.2009.04.012","article-title":"et al.","volume":"54","author":"Simonneau","year":"2009","journal-title":"J. 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