A helicopter perspective on TB biomarkers: pathway and process based analysis of gene expression data provides new insight into TB pathogenesis

PLoS One. 2013 Sep 16;8(9):e73230. doi: 10.1371/journal.pone.0073230. eCollection 2013.

Abstract

Biomarker host genetic signatures are considered key tools for improved early diagnosis of tuberculosis (TB) disease (development). The analysis of gene expression changes based on a limited number of genes or single study designs, however, may not be sufficient for the identification of universal diagnostic biomarker profiles. Here we propose that biological pathway and process based analyses from multiple data sets may be more relevant for identification of key pathways in TB pathogenesis, and may reveal novel candidate diagnostic TB biomarkers. A number of independent genome-wide gene expression studies have recently been performed to study expression of biomarkers for TB disease. We have integrated the results from these independent studies and performed pathway- as well as biological process-based analysis on the total data set. Interestingly, IFNα/β signalling is not the single dominant pathway in the analysis of the total dataset, but combined, functional, analysis of biomarkers suggests a strong dominant role for myeloid cell involvement in inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • Gene Expression Profiling
  • Humans
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Tuberculosis / genetics*

Substances

  • Biomarkers

Grants and funding

The authors acknowledge European Commission Framework Programme 6 TBVAC contract no. LSHP-CT-2003-503367, European Commission Framework Programme 7 NEWTBVAC contract no. HEALTH F3-2009-241745 and European Commission Framework Programme 7 ADITEC contract no. HEALTH.2011.1.4-4 280873 (the text represents the authors’ views and does not necessarily represent a position of the Commission who will not be liable for the use made of such information), The Netherlands Organization for Scientific Research (VENI grant 916.86.115), the Gisela Thier foundation of the Leiden University Medical Center and the Netherlands Leprosy Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.