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A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection

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Title: A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection
Authors: Singhania, A
Verma, R
Graham, CM
Lee, J
Tran, T
Richardson, M
Lecine, P
Leissner, P
Berry, MPR
Wilkinson, RJ
Kaiser, K
Rodrigue, M
Woltmann, G
Haldar, P
O'Garra, A
Item Type: Journal Article
Abstract: Whole blood transcriptional signatures distinguishing active tuberculosis patients from asymptomatic latently infected individuals exist. Consensus has not been achieved regarding the optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Here we show a blood transcriptional signature of active tuberculosis using RNA-Seq, confirming microarray results, that discriminates active tuberculosis from latently infected and healthy individuals, validating this signature in an independent cohort. Using an advanced modular approach, we utilise the information from the entire transcriptome, which includes overabundance of type I interferon-inducible genes and underabundance of IFNG and TBX21, to develop a signature that discriminates active tuberculosis patients from latently infected individuals or those with acute viral and bacterial infections. We suggest that methods targeting gene selection across multiple discriminant modules can improve the development of diagnostic biomarkers with improved performance. Finally, utilising the modular approach, we demonstrate dynamic heterogeneity in a longitudinal study of recent tuberculosis contacts.
Issue Date: 19-Jun-2018
Date of Acceptance: 1-May-2018
URI: http://hdl.handle.net/10044/1/60326
DOI: 10.1038/s41467-018-04579-w
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Issue: 7
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 104803/Z/14/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GAMMA RELEASE ASSAYS
ACTIVE TUBERCULOSIS
IMMUNE-RESPONSE
MYCOBACTERIAL INFECTION
EXPRESSION PROFILES
GENE
BLOOD
SUSCEPTIBILITY
RESISTANCE
BACTERIAL
Adult
Aged
Area Under Curve
Biomarkers
Cohort Studies
Female
Gene Expression Profiling
Gene Library
Humans
Immunosuppressive Agents
Interferon-gamma
Longitudinal Studies
Male
Middle Aged
Mycobacterium tuberculosis
Oligonucleotide Array Sequence Analysis
Phenotype
ROC Curve
Risk
Sequence Analysis, RNA
T-Box Domain Proteins
Transcription, Genetic
Transcriptome
Tuberculosis, Pulmonary
Humans
Mycobacterium tuberculosis
Tuberculosis, Pulmonary
T-Box Domain Proteins
Immunosuppressive Agents
Oligonucleotide Array Sequence Analysis
Area Under Curve
Risk
Cohort Studies
Longitudinal Studies
ROC Curve
Gene Expression Profiling
Sequence Analysis, RNA
Transcription, Genetic
Phenotype
Gene Library
Adult
Aged
Middle Aged
Female
Male
Interferon-gamma
Transcriptome
Biomarkers
Publication Status: Published
Conference Place: England
Article Number: ARTN 2308
Appears in Collections:Department of Infectious Diseases
National Heart and Lung Institute
National Heart and Lung Institute
Faculty of Medicine