The goal of this Sequencing Core is to provide sequencing and analysis services to 3 of the Scientific Projects for a Center for Excellence in Translational Research that focuses on innovative diagnostics for childhood and drug resistant tuberculosis. The core will support the projects by using Next-Generation Sequencing to discover novel biomarkers of drug resistant in well-characterized clinical strains, to characterize mycobacterial DNA fragment that may be present in the urine of patients with active disease and to profile pools of constructed mutants that have undergone in vitro and in vivo selection under drug ? pressure. We will leverage our extensive previous experience in microbial whole genome sequencing and a range of custom analysis tools to ensure the technical success ofthe projects. The results of these studies will be used to lay the framework for development of a rapid and inexpensive diagnostic test that can detect the genetic signature of Mycobacteria tuberculosis and its drug resistant mutants.

Public Health Relevance

Next-generation sequencing technologies enable major advances in the discovery of new biomarkers of drug resistance and the sensitive detection of microbial infection in humans. This project makes use of these innovations to further the development of a rapid diagnostic designed to hasten the diagnosis and appropriate treatment of adults and children with drug sensitive and resistant TB.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-LR-M (J1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
United States
Zip Code
Farhat, Maha R; Jacobson, Karen R; Franke, Molly F et al. (2016) Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis. J Clin Microbiol 54:727-33
Farhat, Maha R; Sultana, Razvan; Iartchouk, Oleg et al. (2016) Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value. Am J Respir Crit Care Med 194:621-30
Rock, Jeremy M; Lang, Ulla F; Chase, Michael R et al. (2015) DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader. Nat Genet 47:677-81
Farhat, M R; Mitnick, C D; Franke, M F et al. (2015) Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment. Int J Tuberc Lung Dis 19:339-41
Farhat, Maha R; Shapiro, B Jesse; Sheppard, Samuel K et al. (2014) A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens. Genome Med 6:101