{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:58:54Z","timestamp":1791647934951,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI152087"],"award-info":[{"award-number":["U01AI152087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL139717"],"award-info":[{"award-number":["R01HL139717"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI176295"],"award-info":[{"award-number":["R21AI176295"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM147512"],"award-info":[{"award-number":["R35GM147512"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23HL153581"],"award-info":[{"award-number":["K23HL153581"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"NSF GRFP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010336","name":"Hellman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001212","name":"Koret Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001212","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stool-based molecular tests provide noninvasive options for pediatric tuberculosis (TB) diagnosis but have lower sensitivity compared to sputum-based tests. Untargeted metagenomic next-generation sequencing (mNGS) on stool could improve sensitivity and identify new gene targets for molecular testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed shotgun mNGS on DNA isolated from stool samples of children undergoing assessment for pulmonary TB in Uganda. We defined the performance of mNGS to identify Mycobacterium tuberculosis (Mtb) against a microbiological reference standard (MRS, TB if sputum Xpert Ultra or culture positive) and a composite reference standard (TB if confirmed or unconfirmed TB). We also compared the accuracy of mNGS against stool-based Xpert Ultra. Finally, we identified enriched genomic loci among Mtb-classified reads.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 176 stool samples of children with a median age of 3.6 years (interquartile range [IQR], 1\u20136 years). Against the MRS, the sensitivities of mNGS with positive TB defined as \u22651, 2, or 5 sequence fragments were 35.5% (95% confidence interval [CI] 19%\u201355%), 25.7% (12%\u201345%), and 19.4% (7%\u201337%), respectively, and specificities 92.6% (87%\u201396%), 97% (93%\u201399%), and 99.3% (96%\u2013100%). Stool Xpert Ultra had similar sensitivity (22.6%) to stool mNGS considering all samples tested. In a head-to-head comparison, stool mNGS had lower sensitivity than stool Xpert Ultra (38.5% vs 53.8%, difference \u221215.3%, 95% CI 14\u201368 vs 25\u201381). mNGS utilized genes encoding rRNA, virulence proteins, and membrane proteins not targeted in current PCR-based platforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metagenomic sequencing of stool DNA did not increase sensitivity of TB detection, but identified novel targets for molecular testing that may support development of more sensitive tests.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag573","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:24:41Z","timestamp":1789673081000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluating Metagenomic Sequencing as a Stool-based Diagnostic in Children With Presumptive Tuberculosis in Uganda"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-3551","authenticated-orcid":false,"given":"Carolina","family":"Agudelo","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California , Berkeley, Berkeley, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Nsereko","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aggrey","family":"Ainebyona","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Andama","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Castro","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, University of California , San Francisco, San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarrah Rose","family":"Mikhail Leung","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California , Berkeley, Berkeley, California ,","place":["USA"]},{"name":"Center for Computational Biology, University of California , Berkeley, Berkeley, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jascent","family":"Nakafeero","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrude","family":"Nanyonga","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5540-879X","authenticated-orcid":false,"given":"Kevin","family":"Nolan","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, University of California , San Francisco, San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3166-3670","authenticated-orcid":false,"given":"Lucas","family":"Teran","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California , Berkeley, Berkeley, California ,","place":["USA"]},{"name":"Joint Medical Program, University of California, Berkeley and University of California, San Francisco , Berkeley, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wambi","sequence":"additional","affiliation":[{"name":"World Alliance for Lung and Intensive Care Medicine in Uganda , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4111-9329","authenticated-orcid":false,"given":"Mark G","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California , Berkeley, Berkeley, California ,","place":["USA"]},{"name":"Center for Computational Biology, University of California , Berkeley, Berkeley, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-2472","authenticated-orcid":false,"given":"Midori","family":"Kato-Maeda","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, University of California , San Francisco, San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-2601","authenticated-orcid":false,"given":"Adithya","family":"Cattamanchi","sequence":"additional","affiliation":[{"name":"Pulmonary Diseases and Critical Care, University of California Irvine , Orange, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8555-5667","authenticated-orcid":false,"given":"Devan","family":"Jaganath","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Disease, University of California , San Francisco, San 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