tbvar: a comprehensive genome variation resource for Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis, along with closely related species, commonly known as M. tuberculosis complex (MTBC), causes tuberculosis in humans and other organisms. Tuberculosis is a disease with high morbidity and mortality, especially in the third world. The genetic variability between clinical isolates of MTBC has been poorly understood, although recent years have seen the re-sequencing of a large number of clinical isolates of MTBC from around the world. The availability of genomic data of multiple isolates in public domain would potentially offer a unique opportunity toward understanding the variome of the organism and the functional consequences of the variations. This nevertheless has been limited by the lack of systematic curation and analysis of data sets available in public domain. In this report, we have re-analyzed re-sequencing data sets corresponding to >450 isolates of MTBC available in public domain to create a comprehensive variome map of MTBC comprising >29 000 single nucleotide variations. Using a systematic computational pipeline, we have annotated potential functional variants and drug-resistance-associated variants from the variome. We have made available this data set as a searchable database. Apart from a user-friendly interface, the database also has a novel option to annotate variants from clinical re-sequencing data sets of MTBC. To the best of our knowledge, tbvar is the largest and most comprehensive genome variation resources for MTBC.Database URL: http://genome.igib.res.in/tbvar/

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.…”

“…The sequence of clinical isolate VPCI591(PRJNA540936), from India was analysed using Maq (Li et al, 2008), inGAP (Qi et al, 2009) and GATK pipeline (McKenna et al, 2010) and G70S variation in MprA was detected and designated as MprA* (Bhattacharyya et al, 2020 (Joshi et al, 2014).…”

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

“…The analysis of genomic [51] and post-genomic data via the construction of large-scale databases [52, 53] will likely lead to an improved understanding of MTB physiology and facilitate the development of more informative molecular assays.…”

Correlation of drug resistance with Single Nucleotide Variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate ofM.tuberculosis

“…The variations were mapped using ANNOVAR software (28). We compared VPCI591 with global datasets of variation totaling to 1553, obtained from GMTV (http://mtb.dobzhanskycenter.org) (29) and tbVar database (http://genome.igib.res.in/tbVar/) (30).…”

“…For non-genic/intergenic variations, the relative distance between the SNV and the downstream gene was determined. From global comparative analysis with tbVar (30) and GMTV (29) database, invariant genes and variations unique to VPCI591 were identified.…”