The goal of this Core is to provide a central system for managing information generated about functions of genes in M. tuberculosis (Mtb) and presenting it to the public. The overall Program Project is anticipated to generate a large amount of data related to identification of functions for genes in the Mtb genome. In particular, major types of genome-scale data to be generated by each of the component projects include: data from sequencing transposon-insertion libraries in knock-down mutants;statistical estimates of changes in essentiality of other genes or regions of the genome for genetic interaction mapping, whole-genome sequencing of phenotypic and suppressor mutants, and gene expression analysis (RNA-Seq) in bacterial mutants. A web site will be developed to provide access to the raw data generated, as well as visual display of derived information (heat maps, genome browser, plots of transposon insertion density, etc.). In addition, we will focus on providing statistical analysis of the data, such as rigorous identification of statistically significant changes in gene expression and gene essentiality. All this data will be combined to make inferences of gene function, for which we will use Gene Ontology (GO) terms. The website will provides links to all sources of evidence supporting each inference, as well as tools for grouping/counting/searching genes by GO term.

Public Health Relevance

M. tuberculosis the most prevalent human pathogen worldwide, and a better understanding of the biology of the organism through the functions of genes in the genome is needed for development of new therapies. The goal of this Core is to compile the data generated by this Program Project and make it available in an accessible, interpreted, and browsable form that will shed light on unknown functions of Mtb proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI107774-02
Application #
8847839
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C (2016) Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection. Curr Opin Microbiol 29:30-6
Cheng, Yu-Shan; Sacchettini, James C (2016) Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance. Biochemistry 55:1107-19
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Murphy, Kenan C; Papavinasasundaram, Kadamba; Sassetti, Christopher M (2015) Mycobacterial recombineering. Methods Mol Biol 1285:177-99
Baer, Christina E; Rubin, Eric J; Sassetti, Christopher M (2015) New insights into TB physiology suggest untapped therapeutic opportunities. Immunol Rev 264:327-43

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