Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.

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 the...

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Autores principales:	Jeroen Maertzdorf, Martin Ota, Dirk Repsilber, Hans J Mollenkopf, January Weiner, Philip C Hill, Stefan H E Kaufmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37f49256568f4f8a8bcadd75e2a2ad37
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spelling	oai:doaj.org-article:37f49256568f4f8a8bcadd75e2a2ad372021-11-18T07:35:32ZFunctional correlations of pathogenesis-driven gene expression signatures in tuberculosis.1932-620310.1371/journal.pone.0026938https://doaj.org/article/37f49256568f4f8a8bcadd75e2a2ad372011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046420/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tuberculosis 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.Jeroen MaertzdorfMartin OtaDirk RepsilberHans J MollenkopfJanuary WeinerPhilip C HillStefan H E KaufmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26938 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeroen Maertzdorf Martin Ota Dirk Repsilber Hans J Mollenkopf January Weiner Philip C Hill Stefan H E Kaufmann Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
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.
format	article
author	Jeroen Maertzdorf Martin Ota Dirk Repsilber Hans J Mollenkopf January Weiner Philip C Hill Stefan H E Kaufmann
author_facet	Jeroen Maertzdorf Martin Ota Dirk Repsilber Hans J Mollenkopf January Weiner Philip C Hill Stefan H E Kaufmann
author_sort	Jeroen Maertzdorf
title	Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
title_short	Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
title_full	Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
title_fullStr	Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
title_full_unstemmed	Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
title_sort	functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/37f49256568f4f8a8bcadd75e2a2ad37
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Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis.

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