Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests.

Proceedings
Cagri OzcaglarKristin P Bennett

Abstract

Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligoforest, using three genetic distance measures. An analysis of topological attributes of the spoligoforest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Th...Continue Reading

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