Frontiers in Immunology (Jul 2020)

An RNA-seq Based Machine Learning Approach Identifies Latent Tuberculosis Patients With an Active Tuberculosis Profile

  • Olivia Estévez,
  • Olivia Estévez,
  • Luis Anibarro,
  • Luis Anibarro,
  • Luis Anibarro,
  • Elina Garet,
  • Elina Garet,
  • Ángeles Pallares,
  • Laura Barcia,
  • Laura Calviño,
  • Cremildo Maueia,
  • Tufária Mussá,
  • Tufária Mussá,
  • Florentino Fdez-Riverola,
  • Florentino Fdez-Riverola,
  • Florentino Fdez-Riverola,
  • Daniel Glez-Peña,
  • Daniel Glez-Peña,
  • Daniel Glez-Peña,
  • Miguel Reboiro-Jato,
  • Miguel Reboiro-Jato,
  • Miguel Reboiro-Jato,
  • Hugo López-Fernández,
  • Hugo López-Fernández,
  • Hugo López-Fernández,
  • Nuno A. Fonseca,
  • Nuno A. Fonseca,
  • Rajko Reljic,
  • África González-Fernández,
  • África González-Fernández

DOI
https://doi.org/10.3389/fimmu.2020.01470
Journal volume & issue
Vol. 11

Abstract

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A better understanding of the response against Tuberculosis (TB) infection is required to accurately identify the individuals with an active or a latent TB infection (LTBI) and also those LTBI patients at higher risk of developing active TB. In this work, we have used the information obtained from studying the gene expression profile of active TB patients and their infected –LTBI- or uninfected –NoTBI- contacts, recruited in Spain and Mozambique, to build a class-prediction model that identifies individuals with a TB infection profile. Following this approach, we have identified several genes and metabolic pathways that provide important information of the immune mechanisms triggered against TB infection. As a novelty of our work, a combination of this class-prediction model and the direct measurement of different immunological parameters, was used to identify a subset of LTBI contacts (called TB-like) whose transcriptional and immunological profiles are suggestive of infection with a higher probability of developing active TB. Validation of this novel approach to identifying LTBI individuals with the highest risk of active TB disease merits further longitudinal studies on larger cohorts in TB endemic areas.

Keywords