Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology

Abstract

BackgroundTuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome.DescriptionHere we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. tuberculosis molecular biology, epidemiology, TB clinical outcome, year and place of isolation, drug resistance profiles and displays the variants across the genome using a dedicated genome browser. GMTV database, which includes 1084 genomes and over 69,000 SNP or Indel variants, can be queried about M. tuberculosis genome variation and putative associations with drug resistance, geographical origin, and clinical stages and outcomes.ConclusionsImplementation of GMTV tracks the pattern of changes of M. tuberculosis strains in different geographical areas, facilitates disease gene discoveries associated with drug resistance or different clinical sequelae, and automates comparative genomic analyses among M. tuberculosis strains.

Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

“…In the current work, 58,025 amino acid substitutions in 1,623 Mtb strains recorded in GMTV database [14] were analyzed for their distribution in the global Mtb population. Information about drug associated mutations was obtained from the TB Drug Resistance Mutation Database [8].…”

“…Induction of drug resistance reversion in MDR-TB by FS-1 made it possible to study this phenomenon on the genetic level. Furthermore, statistical analysis of distribution of polymorphic sites in the global Mtb population based on the data from GMTV database [14] allowed getting insight into functional relations between drug resistance mutations of Mtb. A work hypothesis was that FS-1 could cause an active counter-selection of drug resistant variants from Mtb populations by aggravating the cumulated fitness cost of the drug resistance mutations as it was predicted previously by a mathematical model by Cohen and Murray [15].…”

Modulation of macrophage defense responses by Mycobacterial persistence protein MprA (Rv0981) in human THP-1 cells: effect of single amino acid variation on host-pathogen interactions

“…We identified a SNV (Single Nucleotide Variation) in genomic position G 1097023 A in mprA gene that led to the substitution of an amino acid, glycine to serine at 70 th position (G70S) in one of our clinical isolates VPCI591. This variation was detected in 3% of the global clinical isolates, as analyzed from GMTV database (Chernyaeva et al, 2014) and tbVar database (Joshi et al, 2014) containing about 1553 global clinical isolates of M.tuberculosis. In the light of the identification of MprA as late antigen and its role implied in persistence of M. tuberculosis, we examined the effect SNP.…”

Identification of Novel Efflux Proteins Rv0191, Rv3756c, Rv3008, and Rv1667c Involved in Pyrazinamide Resistance in Mycobacterium tuberculosis

“…Database analysis for mutations in Rv0191, Rv3756c, Rv3008, and Rv1667c. Genome-wide Mycobacterium tuberculosis Variation (GMTV) is a database that covers the whole-genome sequencing information of 1,084 M. tuberculosis isolates from various data sets in different regions of Russia (37). The GMTV database contains data involving molecular biology, epidemiology, tuberculosis clinical data, year, region, and drug resistance information for Mycobacterium tuberculosis, which can be used to identify the genetic variation of drug resistance, clinical outcomes, or pathogens related to geographical distribution.…”