Jump to main content
Jump to site search

Issue 4, 2014
Previous Article Next Article

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

Author affiliations

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

Back to tab navigation

Supplementary files

Publication details

The article was received on 08 Nov 2013, accepted on 07 Jan 2014 and first published on 10 Jan 2014


Article type: Paper
DOI: 10.1039/C3MB70496C
Citation: Mol. BioSyst., 2014,10, 732-740
  • Open access: Creative Commons BY license
  •   Request permissions

    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

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements