Issue 4, 2014

An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis

Abstract

Pulmonary arterial hypertension (PAH) is a major progressive form of pulmonary hypertension (PH) with more than 4800 patients in the United States. 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–cytokine 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.

Graphical abstract: An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis

Supplementary files

Article information

Article type
Paper
Submitted
08 Nov 2013
Accepted
07 Jan 2014
First published
10 Jan 2014
This article is Open Access
Creative Commons BY license

Mol. BioSyst., 2014,10, 732-740

An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis

M. Zhao, E. D. Austin, A. R. Hemnes, J. E. Loyd and Z. Zhao, Mol. BioSyst., 2014, 10, 732 DOI: 10.1039/C3MB70496C

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