{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:31:23Z","timestamp":1792647083122,"version":"4.5.0"},"reference-count":43,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI128344"],"award-info":[{"award-number":["R01AI128344"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Fellowship 152448"],"award-info":[{"award-number":["Fellowship 152448"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Foundation Award 148362"],"award-info":[{"award-number":["Foundation Award 148362"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether \u2018deep\u2019 sequencing can provide additional resolution compared to standard sequencing, using a well-characterized outbreak from the Arctic (2011\u20132012, 50 cases). Samples were sequenced to ~500\u20131000x and reads were aligned to a novel local reference genome generated with PacBio SMRT sequencing. Consensus and heterogeneous variants were identified and compared across genomes. In contrast with previous genomic analyses using ~50x depth, deep sequencing allowed us to identify a novel super-spreader who likely transmitted to up to 17 other cases during the outbreak (35% of the remaining cases that year). It is increasingly evident that within-host diversity should be incorporated into transmission analyses; deep sequencing may facilitate more accurate detection of super-spreaders and transmission clusters. This has implications not only for TB, but all genomic studies of transmission - regardless of pathogen.<\/jats:p>","DOI":"10.7554\/elife.53245","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T19:00:27Z","timestamp":1580756427000},"source":"Crossref","is-referenced-by-count":56,"title":["Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7120-9053","authenticated-orcid":true,"given":"Robyn S","family":"Lee","sequence":"first","affiliation":[{"name":"Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada"},{"name":"Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, Boston, United States"},{"name":"Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Proulx","sequence":"additional","affiliation":[{"name":"Nunavik Regional Board of Health and Social Services, Kuujjuaq, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"McIntosh","sequence":"additional","affiliation":[{"name":"The Research Institute of McGill University Health Centre, Montr\u00e9al, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel A","family":"Behr","sequence":"additional","affiliation":[{"name":"The Research Institute of McGill University Health Centre, Montr\u00e9al, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P","family":"Hanage","sequence":"additional","affiliation":[{"name":"Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, Boston, United States"},{"name":"Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,2,4]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08365","article-title":"RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes","volume":"5","author":"Brettin","year":"2015","journal-title":"Scientific Reports"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1128\/JCM.00486-15","article-title":"Rapid Whole-Genome sequencing of Mycobacterium tuberculosis isolates directly from clinical samples","volume":"53","author":"Brown","year":"2015","journal-title":"Journal of Clinical Microbiology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S2213-2600(13)70231-5","article-title":"Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study","volume":"1","author":"Bryant","year":"2013","journal-title":"The Lancet Respiratory Medicine"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1093\/molbev\/mst028","article-title":"Hierarchical and spatially explicit clustering of DNA sequences with BAPS software","volume":"30","author":"Cheng","year":"2013","journal-title":"Molecular Biology and Evolution"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single Nucleotide Polymorphisms, SnpEff: snps in the genome of Drosophila melanogaster strain w1118; 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