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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis
PLoS ONE, Volume 6, No. 10, Article e26938, Year 2011
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Description
Tuberculosis remains a major health threat and its control depends on improved measures of prevention, diagnosis and treatment. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. Such profiles also reveal fundamental biological mechanisms associated with the pathology of the disease. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These analyses were employed for identification of new disease-associated gene signatures, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed. Functional gene clusters of immunoregulatory interactions involving the JAK-STAT pathway; sensing of microbial patterns by Toll-like receptors and IFN-signaling provide detailed insights into the dysregulation of critical immune processes in TB, involving active expression of both pro-inflammatory and immunoregulatory systems. We conclude that transcriptomics (i) provides a robust system for identification and validation of biosignatures for TB and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis. © 2011 Maertzdorf et al.
Available Materials
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https://efashare.b-cdn.net/share/pmc/articles/PMC3203931/bin/pone.0026938.s003.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3203931/bin/pone.0026938.s004.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3203931/bin/pone.0026938.s005.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3203931/bin/pone.0026938.s006.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3203931/bin/pone.0026938.s007.xls
Authors & Co-Authors
Maertzdorf, Jeroen
Germany, Berlin
Max Planck Institute for Infection Biology
Ota, Martin Okechukwu C.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Repsilber, Dirk
Germany, Dummerstorf
Research Institute for Farm Animal Biology Fbn
Mollenkopf, Hans Joachim
Germany, Berlin
Max Planck Institute for Infection Biology
Weiner, January Mikolaj
Germany, Berlin
Max Planck Institute for Infection Biology
Hill, Philip C.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Kaufmann, Stefan Hugo Ernst
Germany, Berlin
Max Planck Institute for Infection Biology
Statistics
Citations: 168
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0026938
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Randomised Control Trial
Cohort Study
Study Locations
Multi-countries
Gambia