Single nucleotide polymorphisms in Mycobacterium tuberculosis and the need for a curated database

Abstract

Summary Recent advances in DNA sequencing have lead to the discovery of thousands of single nucleotide polymorphisms (SNPs) in clinical isolates of Mycobacterium tuberculosis complex (MTBC). This genetic variation has changed our understanding of the differences and phylogenetic relationships between strains. Many of these mutations can serve as phylogenetic markers for strain classification, while others cause drug resistance. Moreover, SNPs can affect the bacterial phenotype in various ways, which may have an impact on the outcome of tuberculosis (TB) infection and disease. Despite the importance of SNPs for our understanding of the diversity of MTBC populations, the research community is currently lacking a comprehensive, well-curated and user-friendly database dedicated to SNP data. First attempts to catalogue and annotate SNPs in MTBC have been made, but more work is needed. In this review, we discuss the biological and epidemiological relevance of SNPs in MTBC. We then review some of the analytical challenges involved in processing SNP data, and end with a list of features, which should be included in a new SNP database for MTBC.

Consequences of genomic diversity in Mycobacterium tuberculosis

“…In addition, several groups have developed SNP-typing schemes using multilocus sequencing analyses [34–36]. More recently, accumulating WGS data have led to the development of novel SNP-typing methods that rely on a broader understanding of the global MTBC phylogenetic diversity [11]. Some of these methods have been built into highly multiplexed assays [37–40].…”

“…Furthermore, identifying genetic determinants of virulence requires analytical methods that index genomic diversity in a more comprehensive manner as opposed to mere “genotyping”. During the past five years, advances in DNA sequencing technologies have made available many whole-genome sequences of MTBC clinical strains from around the world [11]. This has led to a better understanding of the global phylogenetic diversity of MTBC.…”

Diversity and disease pathogenesis in Mycobacterium tuberculosis

“…For those mutations that occur in the absence of drug resistance, it is even more challenging to determine the functional consequences of different mutations: as noted elsewhere [11], the absence of HGT means that all SNPs in an individual M. tuberculosis genome are in linkage disequilibrium. Therefore, while low-level homoplasy means that SNPs can be usefully applied to measure evolutionary distances among isolates, determining their impact on bacillary function and pathogenesis is not trivial.…”

“…The recent availability of WGS technologies has rejected this model: increasing evidence of strain diversity [7,11], lineage-specific adaptation to host populations [12,13], and microvariation within hosts and communities [14][15][16] instead supports the idea that mycobacterial genetics and, therefore, function, are a significant element in determining the heterogeneous outcomes of infection.…”

DBDiaSNP: An Open-Source Knowledgebase of Genetic Polymorphisms and Resistance Genes Related to Diarrheal Pathogens

“…Large-scale studies have been undertaken throughout the world to identify the antibiotic resistance-associated mutations that are devoted to some specific organism such as GMTV) or which are generalized and hosts mutations or resistance data from different organisms (CRAD, ARDB, CREAM) (Baux et al, 2008;Bharti et al, 2012;Chernyaeva et al, 2014;Dai et al, 2014;Liu and Pop, 2009;McArthur et al, 2013;Stucki and Gagneux, 2013;Vishnoi et al, 2008). The information about pathogens that are implicated in other disorders, including diarrhea, is not disease specific, while our database pertains to clinical isolates of diarrheal pathogens.…”