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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Identification of a 251 gene expression signature that can accurately detect M. tuberculosis in patients with and without HIV co-infection
PLoS ONE, Volume 9, No. 2, Article e89925, Year 2014
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Description
Background: Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV. Methods: We analyzed global gene expression data from peripheral blood mononuclear cell (PBMC) samples of patients that were either mono-infected with HIV or co-infected with HIV/TB and used support vector machines to identify a gene signature that can distinguish between the two classes. We then validated our results using publically available gene expression data from patients mono-infected with TB. Results: Our analysis successfully identified a 251-gene signature that accurately distinguishes patients co-infected with HIV/TB from those infected with HIV only, with an overall accuracy of 81.4% (sensitivity = 76.2%, specificity = 86.4%). Furthermore, we show that our 251-gene signature can also accurately distinguish patients with active TB in the absence of an HIV infection from both patients with a latent TB infection and healthy controls (88.9-94.7% accuracy; 69.2-90% sensitivity and 90.3-100% specificity). We also demonstrate that the expression levels of the 251-gene signature diminish as a correlate of the length of TB treatment. Conclusions: A 251-gene signature is described to (a) detect TB in the presence or absence of an HIV co-infection, and (b) assess response to treatment following anti-TB therapy. © 2014 Dawany et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s004.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s005.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s006.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s007.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3934945/bin/pone.0089925.s008.doc
Authors & Co-Authors
Dawany, Noor B.
United States, Philadelphia
The Wistar Institute
Showe, Louise C.
United States, Philadelphia
The Wistar Institute
Kossenkov, Andrew V.
United States, Philadelphia
The Wistar Institute
Chang, Celia
United States, Philadelphia
The Wistar Institute
Ive, Prudence D.
South Africa, Johannesburg
University of the Witwatersrand
Conradie, Francesca M.
South Africa, Johannesburg
University of the Witwatersrand
Stevens, Wendy Susan
South Africa, Johannesburg
University of the Witwatersrand
Sanne, Ian M.
South Africa, Johannesburg
University of the Witwatersrand
Azzoni, Livio
United States, Philadelphia
The Wistar Institute
Montaner, Luis J.
United States, Philadelphia
The Wistar Institute
Statistics
Citations: 33
Authors: 10
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0089925
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases