{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:02:33Z","timestamp":1780329753359,"version":"3.54.1"},"reference-count":42,"publisher":"Microbiology Society","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant No. 82373649"],"award-info":[{"award-number":["Grant No. 82373649"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background.<\/jats:bold>\n                    The\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    H37Rv reference genome (Lineage 4), sequenced in 1998, may be incomplete and inaccurate due to earlier technology. Moreover, its use is problematic in regions like East Asia where the dominant Beijing lineage (Lineage 2) is prevalent, as it may introduce biases due to lineage-specific genetic differences.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods.<\/jats:bold>\n                    We performed hybrid sequencing to generate high-quality assemblies of a clinically isolated Beijing family strain (A2018772) and a Chinese laboratory-adapted H37Rv strain (H37Rv_CN). Comparative genomic analysis was conducted against the standard H37Rv reference. The impact of reference genome choice on transmission clustering was evaluated using a dataset of 3,359\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    Lineage 2 strains from China.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results.<\/jats:bold>\n                    Comprehensive genomic analysis revealed substantial differences between both studied strains and H37Rv_ref. The Chinese laboratory-adapted H37Rv_CN strain differed by 145 SNPs, 49 InDels and 14 structural variants from the reference genome. The Beijing family clinical isolated strain A2018772 showed even greater divergence with 2,277 SNPs, 373 InDels and 219 structural variants compared to H37Rv_ref, with particular enrichment in PE\/PPE genes and metabolic pathways. Among these variations, a 9.2\u2009kb deletion was prevalent in 89.7% of 78 publicly available Lineage 2 genomes. When applied to transmission analysis of 3,359 Chinese Lineage 2 strains, the A2018772 as a reference genome demonstrated superior performance with higher mapping rates (99.52% vs. 98.72%) and coverage (99.73% vs. 98.50%) compared to H37Rv_ref. This improved resolution resulted in fewer transmission clusters (273 vs. 285) at the 5-SNP threshold, indicating that H37Rv_ref consistently overestimates transmission events in Lineage 2-dominated populations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion.<\/jats:bold>\n                    Our study demonstrates the incompleteness of the H37Rv reference genome and also finds that using a lineage-specific reference genome could significantly improve transmission inference accuracy for Lineage 2 strains, highlighting the need for region-specific genomic references to enhance tuberculosis control strategies in high-burden areas.\n                  <\/jats:p>","DOI":"10.1099\/mgen.0.001688","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:15:31Z","timestamp":1780326931000},"source":"Crossref","is-referenced-by-count":0,"title":["Hybrid sequencing reveals incompleteness of the H37Rv reference genome and highlights lineage-specific genomic divergence in Mycobacterium tuberculosis"],"prefix":"10.1099","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7577-7754","authenticated-orcid":false,"given":"Haiting","family":"Chen","sequence":"first","affiliation":[{"name":"School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou 310016, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, PR 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