期刊
GENOME MEDICINE
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13073-020-00817-3
关键词
Tuberculosis; Diagnostics; Profiling; SNPs; Barcoding; Mycobacteria tuberculosis complex
资金
- Medical Research Council UK [MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1]
- BBSRC UK [BB/R013063/1]
- core AHRI budget (NORAD grant)
- core AHRI budget (SIDA grant)
- National Institutes of Health (NIH) Fogarty International Center Global Infectious Diseases grant entitled Ethiopia-Emory TB Research Training Program [D43TW009127]
- BBSRC LiDO PhD studentship
- BBSRC [BB/R013063/1] Funding Source: UKRI
- MRC [MR/R025576/1, MR/N010469/1, MR/M01360X/1, MR/R020973/1] Funding Source: UKRI
Background: Tuberculosis, caused by bacteria in the Mycobacterium tuberculosis complex (MTBC), is a major global public health burden. Strain-specific genomic diversity in the known lineages of MTBC is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Fast and accurate tracking of MTBC strains is therefore crucial for infection control, and our previous work developed a 62single nucleotide polymorphism (SNP) barcode to inform on the phylogenetic identity of 7 human lineages and 64 sub-lineages. Methods: To update this barcode, we analysed whole genome sequencing data from 35,298 MTBC isolates (similar to 1 million SNPs) covering 9 main lineages and 3 similar animal-related species (M. tuberculosis var. bovis, M. tuberculosis var. caprae and M. tuberculosis var. orygis). The data was partitioned into training (N = 17,903, 50.7%) and test (N = 17,395, 49.3%) sets and were analysed using an integrated phylogenetic tree and population differentiation (FST) statistical approach. Results: By constructing a phylogenetic tree on the training MTBC isolates, we characterised 90 lineages or sublineages or species, of which 30 are new, and identified 421 robust barcoding mutations, of which a minimal set of 90 was selected that included 20 markers from the 62-SNP barcode. The barcoding SNPs (90 and 421) discriminated perfectly the 86 MTBC isolate (sub-)lineages in the test set and could accurately reconstruct the clades across the combined 35k samples. Conclusions: The validated 90 SNPs can be used for the rapid diagnosis and tracking of MTBC strains to assist public health surveillance and control. To facilitate this, the SNP markers have now been incorporated into the TBProfiler informatics platform (https://github.com/jodyphelan/TBProfiler).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据