TBVAR:A COMPREHENSIVE GENOME VARIATION RESOURCE FOR MYCOBACTERIUM TUBERCULOSIS

Abstract

Tuberculosis (TB) is the second highest cause of mortality after HIV/AIDS and is one of the leading public health problems in the developing world, caused by the fastidious pathogen Mycobacterium tuberculosis (MTB). The increasing resistance to anti-TB drugs and the recalcitrant nature of tenacious infections give rise to arduous challenges for the treatment of TB. Although, the advent of Next Generation Sequencing (NGS) has led to the discovery of thousands of Single Nucleotide Polymorphisms (SNPs) in clinical isolates of Mycobacterium tuberculosis complex (MTBC), this genetic variability amongst different isolates is poorly understood. MTBC strain variation is known to play a role in the outcome of TB infection and disease and can also affect the bacterial phenotype including drug resistance. This work is aimed towards the analysis of high coverage resequencing datasets available in public domain. A data analysis pipeline was designed and used to reassemble, annotate and catalogue the SNPs in each of the datasets from over 400 different isolates. All the deciphered information was used to compile a comprehensive, well-curated and user-friendly database dedicated to the SNP data, along-with an interface for quick annotation of variations. Our analysis revealed a broad repertoire of more than 29,000 variations in MTB, in comparison to the H37Rv reference genome. 21,616 variations were found to be novel, significantly adding to the ensemble of known SNPs in MTB and 5,394 were predicted to be potentially deleterious in 2,407 genes as predicted by SIFT. To the best of our knowledge tbvar is the largest and most comprehensive genome variation resource for M. tuberculosis. It not only offers a user friendly interface for annotating SNPs but also provides a starting point towards clinical application of variant information. The database is available as a free online resource at http://genome.igib.res.in/tbvar/