133: Culture-Independent Meta‑Pangenomics Reveals Gut Genome Links to Child Growth

️ Episode 133: Culture-Independent Meta‑Pangenomics Reveals Gut Genome Links to Child Growth In this episode of PaperCast Base by Base, we explore how long‑read metagenomics enables recovery of complete metagenome‑assembled genomes directly from fecal samples of Malawian toddlers and applies meta‑pangenomics and microbial GWAS to connect microbial genetics with pediatric linear growth and breastfeeding status. Study Highlights:Long‑read sequencing with PacBio and Oxford Nanopore generated 44–64 times more complete genomes per gigabase than short‑read approaches, with PacBio yielding the most accurate and cost‑effective assemblies. A longitudinal cohort produced 986 complete genomes, 839 circular, across 47 samples from eight children and markedly improved taxonomic classification in both resequenced and naive samples. Meta‑pangenome and microbial genome‑wide association analyses across Prevotella, Faecalibacterium, Megasphaera, Bifidobacterium and others identified gene‑level signatures linked to linear growth trajectories and breastfeeding. Temporal analyses showed greater microbial genome instability in children with declining length‑for‑age Z scores and prophage integrations varied by genus and phenotype. Cross‑platform comparisons established robust methods, recommended assembler choices, and modeled data‑to‑genome recovery to guide study design. Conclusion:This work establishes a culture‑independent, strain‑resolved framework for linking the infant gut microbiome to growth outcomes and sets a new standard for microbiome association studies and future intervention design. Reference:Minich, J.J., Allsing, N., Din, M.O., Tisza, M.J., Maleta, K., McDonald, D., Hartwick, N., Mamerto, A., Brennan, C., Hansen, L., Shaffer, J., Murray, E.R., Duong, T., Knight, R., Stephenson, K., Manary, M.J., & Michael, T.P. (2025). Culture‑independent meta‑pangenomics enabled by long‑read metagenomics reveals associations with pediatric undernutrition. Cell, 188, 1–21. https://doi.org/10.1016/j.cell.2025.08.020 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.castos.com/

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