Comparison of in silico predicted Mycobacterium tuberculosis spoligotypes and lineages from whole genome sequencing data
Résumé
Bacterial strain-types in the Mycobacterium tuberculosis complexunderlie tuberculosis disease, and have been associated with drugresistance, transmissibility, virulence, and host–pathogeninteractions. Spoligotyping was developed as a molecular genotypingtechnique used to determine strain-types, though recent advances inwhole genome sequencing (WGS) technology have led to theircharacterization using SNP-based sub-lineage nomenclature.Notwithstanding, spoligotyping remains an important tool and thereis a need to study the congruence between spoligotyping-based andSNP-based sub-lineage assignation. To achieve this, an in silicospoligotype prediction method (“Spolpred2”) was developed andintegrated into TB-Profiler. Lineage and spoligotype predictionswere generated for > 28 k isolates and the overlap betweenstrain-types was characterized. Major spoligotype families detectedwere Beijing (25.6%), T (18.6%), LAM (13.1%), CAS (9.4%), and EAI(8.3%), and these broadly followed known geographic distributions.Most spoligotypes were perfectly correlated with the main MTBClineages (L1-L7, plus animal). Conversely, at lower levels of thesub-lineage system, the relationship breaks down, with only 65% ofspoligotypes being perfectly associated with a sub-lineage at thesecond or subsequent levels of the hierarchy. Our work supports theuse of spoligotyping (membrane or WGS-based) for low-resolutionsurveillance, and WGS or SNP-based systems for higher-resolutionstudies.