In silico region of difference (RD) analysis of Mycobacterium tuberculosis complex from sequence reads using RD-Analyzer. (December 2016)

• Record Type: Journal Article
• Authors: Faksri, Kiatichai; Xia, Eryu; Tan, Jun; Teo, Yik-Ying; Ong, Rick
• Is Part Of: BMC genomics. Volume 17:Number 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Region of difference analysis -- Mycobacterium tuberculosis complex -- Whole-genome sequence analysis; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-3213-1
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background Whole-genome sequencing is increasingly used in clinical diagnosis of tuberculosis and study ofMycobacterium tuberculosis complex (MTC). MTC consists of several genetically homogenous mycobacteria species which can cause tuberculosis in humans and animals. Regions of difference (RDs) are commonly regarded as gold standard genetic markers for MTC classification. Results We develop RD-Analyzer, a tool that can accurately infer the species and lineage of MTC isolates from sequence reads based on the presence and absence of a set of 31 RDs. Applied on a publicly available diverse set of 377 sequenced MTC isolates from known major species and lineages, RD-Analyzer achieved an accuracy of 98.14 % (370/377) in species prediction and a concordance of 98.47 % (257/261) inMycobacterium tuberculosis lineage prediction compared to predictions based on single nucleotide polymorphism markers. By comparing respective sequencing read depths on each genomic position between isolates of different sublineages, we were able to identify the known RD markers in different sublineages of Lineage 4 and provide support for six potential delineating markers having high sensitivities and specificities for sublineage prediction. An extended version of RD-Analyzer was thus developed to allow user-defined RDs for lineage prediction. Conclusions RD-Analyzer is a useful and accurate tool for species, lineage and sublineage prediction using known RDs of MTC from sequence reads and is extendable to accepting user-defined RDs for analysis. RD-Analyzer is written in Python and is freely available athttps://github.com/xiaeryu/RD-Analyzer .