{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:18Z","timestamp":1792790418358,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Microbiology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Centers for Disease Control and Prevention","award":["75D301-22-C-14717"],"award-info":[{"award-number":["75D301-22-C-14717"]}]},{"name":"Minderoo Foundation","award":["CLB-3502"],"award-info":[{"award-number":["CLB-3502"]}],"id":[{"id":"https:\/\/ror.org\/0289t9g81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH\/NIAID","award":["R24AI118629"],"award-info":[{"award-number":["R24AI118629"]}]},{"name":"NIH\/NIGMS","award":["T32GM007198"],"award-info":[{"award-number":["T32GM007198"]}]},{"name":"NIH\/NIA","award":["F30AG094275"],"award-info":[{"award-number":["F30AG094275"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>Standard metagenomics resolves microbial communities only in relative terms and at coarse taxonomic resolution, obscuring how individual strains change in absolute abundance and evolve within a host. We present long-read quantiomics (LRQ), a quantitative metagenomics platform coupling long-read sequencing with plasmid-based internal standards to recover high-quality genomes, including from degraded or low-input stool, and measure absolute, genome-resolved strain abundances. We validate LRQ using large plasmid standards and bacterial spike-ins, then apply it to eight years of dense sampling from an individual with colonic Crohn's disease. LRQ resolves co-resident strains of the same species following opposing trajectories with inflammation. Escherichia coli, long treated as a single pathobiont, separates into two sub-populations with opposing inflammation responses; the inflammation-associated lineage carries an immune-evasion module of virulence-associated metal-acquisition, biofilm, capsule and toxin genes. We observe genome-wide adaptive sweeps on timescales matched to disease incidence. LRQ therefore converts long-read metagenomics from a genome-recovery tool into a quantitative framework providing absolute, strain-level measurement of microbial ecology and evolution.<\/jats:p>","DOI":"10.64898\/2026.09.28.754546","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:25:14Z","timestamp":1790745914000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics"],"prefix":"10.64898","author":[{"given":"M. Omar","family":"Din","sequence":"first","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitriona","family":"Brennan","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshu","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Oles","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Patel","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Birmingham","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilara M.","family":"Sevilir","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Hansen","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian M.","family":"Wright","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Ambre","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meika","family":"Tomita","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Boyer","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Ackermann","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McDonald","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kralicek","sequence":"additional","affiliation":[{"name":"Midwestern University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Hecht","sequence":"additional","affiliation":[{"name":"Loyola University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Hasty","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Smarr","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Knight","sequence":"additional","affiliation":[{"name":"University of California San Diego;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.28.754546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:25:14Z","timestamp":1790745914000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.28.754546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.09.28.754546","relation":{},"subject":[],"published":{"date-parts":[[2026,9,29]]},"subtype":"preprint"}}