Perspectives for systems biology in the management of tuberculosis.

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
Competing Interests: Conflict of Interest: I. Kontsevaya has nothing to disclose. Conflict of interest: C. Lange reports personal fees from Chiesi, Gilead, Janssen, Lucane, Novartis, Oxoid, Berlin Chemie, Thermofisher and Oxfordimmunotec, outside the submitted work. Conflict of interest: P. Comella-del-Barrio has nothing to disclose. Conflict of interest: C. Coarfa has nothing to disclose. Conflict of interest: A.R. DiNardo has nothing to disclose. Conflict of interest: S.H. Gillespie reports non-financial support from LifeArc, during the conduct of the study; and other support from ODx Innovations, outside the submitted work. Conflict of interest: M. Hauptmann has nothing to disclose. Conflict of interest: C. Leschczyk has nothing to disclose. Conflict of interest: A.M. Mandalakas has nothing to disclose. Conflict of interest: A. Martinecz has nothing to disclose. Conflict of interest: M. Merker has nothing to disclose. Conflict of interest: S. Niemann reports grants from German Center for Infection Research, Excellenz Cluster Precision Medicine in Chronic Inflammation EXC 2167, and Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG), during the conduct of the study. Conflict of interest: M. Reimann has nothing to disclose. Conflict of interest: O. Rzhepishevska has nothing to disclose. Conflict of interest: U.E. Schaible has nothing to disclose. Conflict of interest: K.M. Scheu has nothing to disclose. Conflict of interest: E. Schurr has nothing to disclose. Conflict of interest: P. Abel zur Wiesch has nothing to disclose. Conflict of interest: J. Heyckendorf has nothing to disclose.
(Copyright ©The authors 2021.)