Model-Based Integration of Genomics and Metabolomics Reveals SNP Functionality in Mycobacterium Tuberculosis
Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis Ove Øyåsa,b,1, Sonia Borrellc,d,1, Andrej Traunerc,d,1, Michael Zimmermanne, Julia Feldmannc,d, Thomas Liphardta,b, Sebastien Gagneuxc,d, Jörg Stellinga,b, Uwe Sauere, and Mattia Zampierie,2 aDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; bSIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; cDepartment of Medical Parasitoloy and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; dUniversity of Basel, 4058 Basel, Switzerland; and eInstitute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved March 2, 2020 (received for review September 12, 2019) Human tuberculosis is caused by members of the Mycobacterium infection of macrophages (29–32). Beyond analyses of individual tuberculosis complex (MTBC) that vary in virulence and transmis- laboratory strains, however, no systematic characterization and sibility. While genome-wide association studies have uncovered comparative analysis of intrinsic metabolic differences across several mutations conferring drug resistance, much less is known human-adapted MTBC clinical strains has been performed. about the factors underlying other bacterial phenotypes. Variation If the metabolic and other phenotypic diversity between in the outcome of tuberculosis infection and diseases has been MTBC strains contributes to and modulates pathogenicity, an attributed primarily to patient and environmental factors, but obvious question is: Which elements of the limited genetic di- recent evidence indicates an additional role for the genetic diver- versity in the MTBC are responsible for phenotypic strain di- sity among MTBC clinical strains.
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