Evalutation of three methods searching resistant-related mutations in mycobacterium tuberculosis genome

Abstract:

[Objective] The emergence of durg-resistant Mycobacterium tuberculosis brought a tough challenge to tuberculosis treatment. [Methods] Considering the lack of homologous recombination in Mycobacterium tuberculosis's genome, the mutation strongly related to resistance could be efficiently confirmed by genome-wide association analysis. However, many resistance-related mutations had yet been found by existing methods. To calculate resistant-related mutations, researchers commonly used some methods similar to genome-wide association analysis (GWAS), which mainly included genome-wide efficient mixed model association (GEMMA), phylogenetic convergence test (phyc), plink. To find the better method among the three methods when calculating resistant-related SNPs on non-mobile antibiotic resistance gene, the genomes of 1504 M. tuberculosis strains from Hunan province and National Center of Biotechnology Information was obtained with their phenotypes of three first-line antibiotics (isoniazid, rifampicin, ethambutol). The three methods were performed to calculate the association between phenotype and known or novel SNPs related to resistance, and their sensibility and specificity were evaluated by the resistant-related SNPs got by the three methods. [Results] Phyc was able to search more known resistance-related SNPs with the sensibility and specificity higher than 52.49%.[Conclusion] Phyc is the most accurate in predicting the SNP related to drug resistance of Mycobacterium tuberculosis, but considering the update of running time and phenotypic data, the results of GEMMA and plink should also be used as a reference.