Journal article
An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis
Molecular BioSystems, Vol.10(4), pp.732-740
2014
Appears in Cancer Research Cluster Research Collection
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. This journal is © 2014 The Royal Society of Chemistry.
Details
- Title
- An evidence-based knowledgebase of pulmonary arterial hypertension to identify genes and pathways relevant to pathogenesis
- Authors
- Min Zhao (Author) - Vanderbilt University School of Medicine, United StatesE D Austin (Author) - Vanderbilt University School of Medicine, United StatesA R Hemnes (Author) - Vanderbilt University School of Medicine, United StatesJ E Loyd (Author) - Vanderbilt University School of Medicine, United StatesZ Zhao (Author) - Vanderbilt University School of Medicine, United States
- Publication details
- Molecular BioSystems, Vol.10(4), pp.732-740
- Publisher
- Royal Society of Chemistry (R S C) Publications
- Date published
- 2014
- DOI
- 10.1039/c3mb70496c
- ISSN
- 1742-206X
- Copyright note
- Copyright © 2014, The Authors. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
- Organisation Unit
- School of Science and Engineering - Legacy; Cancer Research Cluster; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99448979002621
- Output Type
- Journal article
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