Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics
- 1University of California San Diego
Abstract
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.
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BibTeX
@misc{din2026genomeresolved,
title = {{Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics}},
author = {M. O. Din and C. Brennan and J. Zhao and R. Oles and L. Patel and A. Birmingham and D. M. Sevilir and L. Hansen and G. M. Wright and M. Ambre and M. Tomita and T. Boyer and A. Gonzalez and G. Ackermann and D. McDonald and S. Kralicek and G. Hecht and J. Hasty and L. Smarr and R. Knight},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.754546},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.754546v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics
AU - M. O. Din
AU - C. Brennan
AU - J. Zhao
AU - R. Oles
AU - L. Patel
AU - A. Birmingham
AU - D. M. Sevilir
AU - L. Hansen
AU - G. M. Wright
AU - M. Ambre
AU - M. Tomita
AU - T. Boyer
AU - A. Gonzalez
AU - G. Ackermann
AU - D. McDonald
AU - S. Kralicek
AU - G. Hecht
AU - J. Hasty
AU - L. Smarr
AU - R. Knight
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.754546
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.754546v1
AB - 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.
ER -