A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack?

Adithya Cattamanchi mail,
Nicholas D. Walter,
John Z. Metcalfe,
J. Lucian Davis

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Citation: Cattamanchi A, Walter ND, Metcalfe JZ, Davis JL (2013) A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack? PLoS Med 10(10): e1001539. doi:10.1371/journal.pmed.1001539
Published: October 22, 2013
Copyright: © 2013 Cattamanchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: AC (K23 HL094141), NW (K12 HL090147), and JZM (K23 AI09425) are supported by career development awards from the U.S. National Institutes of Health. This work is also supported by the National Center for Advancing Translational Sciences, National Institutes of Health (UCSF-CTSI KL2 TR000143). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. None of the funders played any role in the preparation of this article.
Competing interests: J. Lucian Davis is involved in additional research concerning blood gene expression profiling and tuberculosis. The other authors have declared that no competing interests exist.
Provenance: Commissioned; not externally peer reviewed.

Linked Research Article

This Perspective discusses the following new study published in PLOS Medicine:
Kaforou M, Wright VJ, Oni T, French N, Anderson ST, et al. (2013) Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study. PLoS Med 10(10): e1001538. doi:10.1371/journal.pmed.1001538.
Using a microarray-based approach, Michael Levin and colleagues develop a disease risk score to distinguish active from latent tuberculosis, as well as tuberculosis from other diseases, using whole blood samples.

Analysis of whole-genome RNA expression in human clinical samples is a relatively novel approach to biomarker development. The pattern of RNA expression (i.e., transcriptional signature) can provide a “biological snapshot” of the immune response to physiological stressors, and specific disease states may produce distinct transcriptional signatures. In this week's issue of PLOS Medicine, Michael Levin and colleagues report that a blood RNA transcriptional signature can be used to diagnose active tuberculosis (TB) in high HIV/TB prevalence settings. Using blood samples from patients referred for TB evaluation at three sites in Cape Town, South Africa (cases from an outpatient TB clinic; controls from two hospitals) and one district hospital in Northern Malawi, the authors identified a minimal set of 44 transcripts that distinguished patients with TB from patients confirmed to have an alternative diagnosis. They then converted the complex expression data into a simple-to-calculate disease risk score, which was highly sensitive (93%, 95% CI [83–100]) and specific (88%, 95% CI [74–97]) for active TB.