{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:37Z","timestamp":1788269017986,"version":"build-2803163510"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Large molecular inversions in the genome of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb) due to factors like the presence of insertion sequences and transposases are widely known. However, smaller inversions within coding sequences and non-coding control elements are rarely reported. The present study aims to identify inversions and their potential impact on Mtb biology in a lineage-specific manner. Structural variants (SVs) could only be detected by long reads. For this, we simulated long reads by\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      assembling the short-read sequencing data sets and subsequently aligned representative strains from each lineage using the Progressive Mauve algorithm. Independently, long-read sequencing from the Pacific Biosciences platform was acquired and analyzed using the structural variant identification method. Variants were merged, and Fisher\u2019s exact test was carried out to identify the inversion association with lineages. To visualize deoxyribonucleic acid (DNA) features, the DNA-features-viewer tool was used. Simulated reads from short-read sequencing gave indications of lineage (L)-specific inversions. The long-read sequencing approach led to the identification of seven unique inversions: two positively associated with L1, one positively associated with L3, two negatively associated with L4, and two positively associated with L3 but negatively associated with L4 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). The inversions encompassed primarily non-essential genes like\n                      <jats:italic toggle=\"yes\">sdaA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">dosT<\/jats:italic>\n                      , Rv2026c,\n                      <jats:italic toggle=\"yes\">dnaE2<\/jats:italic>\n                      , Rv1341, Rv1342, and\n                      <jats:italic toggle=\"yes\">lprD<\/jats:italic>\n                      . An interesting inversion was observed in the upstream control element of\n                      <jats:italic toggle=\"yes\">purB<\/jats:italic>\n                      and Rv0776c. The study sheds light on small inversions that may be causing alterations in expression, formation of fusion genes, and nonsense mutations that may have a role in lineage-specific phenotypic changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The role of mutations like SNPs and INDELs and their association with drug resistance is well known in\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb). However, structural variations, especially inversions, are largely overlooked and unreported. In this paper, publicly available whole-genome sequencing datasets from Illumina and Pacific Biosciences\u2013Oxford Nanopore Technologies platform have been used to detect inversions and report seven unreported Mtb lineage-specific small inversions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02469-25","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:01:12Z","timestamp":1786366872000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Lineage-associated small inversions disrupt\n                    <i>dosT<\/i>\n                    ,\n                    <i>dnaE2<\/i>\n                    , and a promoter-adjacent region in some\n                    <i>Mycobacterium tuberculosis<\/i>\n                    isolates"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0584-5726","authenticated-orcid":true,"given":"Nikhil","family":"Bhalla","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056d84691","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet","place":["Stockholm, Sweden"]},{"id":[{"id":"https:\/\/ror.org\/03j4rrt43","id-type":"ROR","asserted-by":"publisher"}],"name":"Translational Health Group, International Centre for Genetic Engineering and Biotechnology","place":["New Delhi, India"]},{"id":[{"id":"https:\/\/ror.org\/04gzb2213","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Delhi South Campus","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Goswami","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gzb2213","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry, University of Delhi South Campus","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08148-z"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.13917"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.102192"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00129"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2005.09.009"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092203"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/119.4.771"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007332"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau5238"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00687-09"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404172101"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005762"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4498-z"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00527-24"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000382"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084971"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv033"},{"key":"e_1_3_5_19_2","unstructured":"Seemann T. 2025. tseemann\/shovill [Internet]. Available from: https:\/\/github.com\/tseemann\/shovill. Retrieved 21 Jul 2025."},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0650-x"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae311"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011147"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v025.i01"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43588-021-00073-4"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz041"},{"key":"e_1_3_5_29_2","unstructured":"Sedlazeck F. 2025. Fritzsedlazeck\/SURVIVOR [Internet]. Available from: https:\/\/github.com\/fritzsedlazeck\/SURVIVOR. Retrieved 21 Jul 2025."},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-65779-9"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0640-8"},{"key":"e_1_3_5_32_2","first-page":"289","article-title":"Genes of Mycobacterium tuberculosis H37Rv downregulated in the attenuated strain H37Ra are restricted to M. tuberculosis complex species","volume":"24","author":"Rindi L","year":"2001","unstructured":"Rindi L, Lari N, Garzelli C. 2001. Genes of Mycobacterium tuberculosis H37Rv downregulated in the attenuated strain H37Ra are restricted to M. tuberculosis complex species. New Microbiol 24:289\u2013294.","journal-title":"New Microbiol"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01449-08"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705054104"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2010.03.013"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1707716"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftac046"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01773-21"}],"container-title":["Microbiology Spectrum"],"original-title":[],"contributor":[{"given":"Fairuz Hassan","family":"Abdullah Tawgozy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]},{"given":"Arijit","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]},{"given":"Shankar","family":"Manoharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"reviewer"}]}],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02469-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02469-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:08:57Z","timestamp":1788268137000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02469-25"}},"subtitle":[],"editor":[{"given":"Felix Ngosa","family":"Toka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1128\/spectrum.02469-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02469-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2025-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02469-25"}}