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Performance evaluation of core genome multilocus sequence typing for genotyping of Mycobacterium tuberculosis strains in China: based on multicenter, population-based collection

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Abstract

Purpose

To evaluate the performance of core genome multilocus sequence typing (cgMLST) for genotyping Mycobacterium tuberculosis (M.tuberculosis) Strains in regions where the lineage 2 strains predominate.

Methods

We compared clustering by whole-genome SNP typing with cgMLST clustering in the analysis of WGS data of 6240 strains from five regions of China. Using both the receiver operating characteristic (ROC) curve and epidemiological investigation to determine the optimal threshold for defining genomic clustering by cgMLST. The performance of cgMLST was evaluated by quantifying the sensitivity, specificity and concordance of clustering between two methods. Logistic regression was used to gauge the impact of strain genetic diversity and lineage on cgMLST clustering.

Results

The optimal threshold for cgMLST to define genomic clustering was determined to be ≤ 10 allelic differences between strains. The overall sensitivity and specificity of cgMLST averaged 99.6% and 96.3%, respectively; the concordance of clustering between two methods averaged 97.1%. Concordance was significantly correlated with strain genetic diversity and was 3.99 times (95% CI, 2.94–5.42) higher in regions with high genetic diversity (π > 1.55 × 10–4) compared to regions with low genetic diversity. The difference missed statistical significance, while concordance for lineage 2 strains (96.8%) was less than that for lineage 4 strains (98.3%).

Conclusion 

cgMLST showed a discriminatory power comparable to whole-genome SNP typing and could be used to genotype clinical M.tuberculosis strains in different regions of China. The discriminative power of cgMLST was significantly correlated with strain genetic diversity and was slightly lower with strains from regions with low genetic diversity.

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Data availability

Whole-genome sequencing (WGS) data used in this study have been previously published and are cited in the Methods section of the paper. These WGS data also are available in the Genome Sequence Archive (https://bigd.big.ac.cn/gsa) under BioProject CRA003250, PRJCA010372, PRJCA008815, and PRJCA008816, and the Europen Nucleotide Archive (https://www.ebi.ac.uk/ena/browser/home) under BioProject PRJEB23157.

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Funding

This study was made possible by the generous support of the Shanghai Municipal Science and Technology Major Project (ZD2021CY001) and National Natural Science Foundation of China (82272376).

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Authors and Affiliations

  1. Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Fudan University, 131 Dongan Road, Shanghai, 200032, China

    Zhuo Quan, Meng Li, Yiwang Chen, Jialei Liang & Qian Gao

  2. Laboratorio de Genética Molecular, CMBC, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, Venezuela

    Howard Takiff

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  1. Zhuo Quan
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  2. Meng Li
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Contributions

All authors contributed to the study conception and design. Z.Q. and M.L. performed the material preparation, data collection, and data analysis. The first draft of the manuscript was written by Z.Q. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qian Gao.

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Quan, Z., Li, M., Chen, Y. et al. Performance evaluation of core genome multilocus sequence typing for genotyping of Mycobacterium tuberculosis strains in China: based on multicenter, population-based collection. Eur J Clin Microbiol Infect Dis 43, 297–304 (2024). https://doi.org/10.1007/s10096-023-04720-8

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