@article{f14bf342011d46c5b6a862a537d43640,
title = "Immunometabolic signatures predict risk of progression to active tuberculosis and disease outcome",
abstract = "There remains a pressing need for biomarkers that can predict who will progress to active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (MTB) bacterium. By analyzing cohorts of household contacts of TB index cases (HHCs) and a stringent non-human primate (NHP) challenge model, we evaluated whether integration of blood transcriptional profiling with serum metabolomic profiling can provide new understanding of disease processes and enable improved prediction of TB progression. Compared to either alone, the combined application of pre-existing transcriptome- and metabolome-based signatures more accurately predicted TB progression in the HHC cohorts and more accurately predicted disease severity in the NHPs. Pathway and data-driven correlation analyses of the integrated transcriptional and metabolomic datasets further identified novel immunometabolomic signatures significantly associated with TB progression in HHCs and NHPs, implicating cortisol, tryptophan, glutathione, and tRNA acylation networks. These results demonstrate the power of multi-omics analysis to provide new insights into complex disease processes.",
keywords = "Biomarker, Host-pathogen interaction, Household contact, Inflammation, Metabolomics, Rhesus macaque, Transcriptomics, Tuberculosis",
author = "{GC6-74 Consortium} and Duffy, {Fergal J.} and January Weiner and Scott Hansen and Tabb, {David L.} and Sara Suliman and Ethan Thompson and Jeroen Maertzdorf and Smitha Shankar and Gerard Tromp and Shreemanta Parida and Drew Dover and Axthelm, {Michael K.} and Sutherland, {Jayne S.} and Dockrell, {Hazel M.} and Ottenhoff, {Tom H.M.} and Scriba, {Thomas J.} and Picker, {Louis J.} and Gerhard Walzl and Kaufmann, {Stefan H.E.} and Zak, {Daniel E.} and R. Golinski and M. Jacobson and G. McEwen and Black, {G. F.} and {Van Der Spuy}, G. and K. Stanley and M. Kriel and N. DuPlessis and N. Nene and Loxton, {A. G.} and Chegou, {N. N.} and M. Fisher and H. Mahomed and J. Hughes and K. Downing and A. Penn-Nicholson and H. Mulenga and B. Abel and M. Bowmaker and B. Kagina and W. Kwong and Hanekom, {C. W.} and Klein, {M. R.} and Haks, {M. C.} and {F ranken}, {K. L.} and A. Geluk and {Van Meijgaarden}, {K. E.} and Joosten, {S. A.} and {Van Baarle}, D. and F. Miedema",
note = "Publisher Copyright: Copyright {\textcopyright} 2019 Duffy, Weiner, Hansen, Tabb, Suliman, Thompson, Maertzdorf, Shankar, Tromp, Parida, Dover, Axthelm, Sutherland, Dockrell, Ottenhoff, Scriba, Picker, Walzl, Kaufmann, Zak and The GC6-74 Consortium. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
doi = "10.3389/fimmu.2019.00527",
language = "English (US)",
volume = "10",
journal = "Frontiers in immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "MAR",
}