journal.pone.0026938.PDF 487,72KB
1000 Titel
  • Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis
1000 Autor/in
  1. Maertzdorf, Jeroen |
  2. Ota, Martin |
  3. Repsilber, Dirk |
  4. Mollenkopf, Hans J. |
  5. Weiner, January |
  6. Hill, Philip C. |
  7. Kaufmann, Stefan H. |
1000 Erscheinungsjahr 2011
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2011-10-28
1000 Erschienen in
1000 Quellenangabe
  • 6(10): e26938
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2011
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Blood
lokal Gene regulation
lokal Immune response
lokal Tuberculosis diagnosis and management
lokal Tuberculosis
lokal Gene expression
lokal Genetic networks
lokal Mycobacterium tuberculosis
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. Bill & Melinda Gates Foundation through the Grand Challenges in Global Health Initiative |
1000 Fördernummer
  1. 37772
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bill & Melinda Gates Foundation through the Grand Challenges in Global Health Initiative |
    1000 Förderprogramm -
    1000 Fördernummer 37772
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403054.rdf
1000 Erstellt am 2017-06-14T10:58:02.550+0200
1000 Erstellt von 21
1000 beschreibt frl:6403054
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet Tue Mar 30 11:42:41 CEST 2021
1000 Objekt bearb. Tue Mar 30 11:42:41 CEST 2021
1000 Vgl. frl:6403054
1000 Oai Id
  1. |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source