Phylogenetic inconsistency of pairwise SNP clustering for inferring tuberculosis transmission in a high-burden, endemic setting: a case study from Thailand
Comparative genomic analysis reveals phylogenetic inconsistency in pairwise SNP clustering for tuberculosis, indicating the need for tree-based methods in high-burden settings.
Key Points
To assess the phylogenetic consistency and reliability of standard pairwise single nucleotide polymorphism (pwSNP) distance thresholds for delineating tuberculosis transmission clusters across contrasting epidemiological settings.
Evaluated pwSNP distance clustering across cutoff thresholds from 1 to 25 SNPs against a monophyly-constrained, tree-based clustering approach.
Analyzed whole-genome sequencing data from two cohorts: a low-burden UK dataset (N = 390) and a high-burden Thai dataset (N = 3,341) with persistent transmission and non-systematic sampling.
In the UK dataset, pwSNP clustering at thresholds of ≥12 SNPs produced entirely monophyletic clusters and high concordance with phylogenetic tree-based clustering.
In the Thai dataset, pwSNP clustering frequently generated non-monophyletic clusters across all tested cutoffs up to 25 SNPs, achieving substantial concordance with tree-based methods only at thresholds of ≥22 SNPs.
Large cluster size, wide sampling time spans, elevated maximum intra-cluster distance, and mixed infections were identified as factors driving non-monophyletic and spurious genetic links.