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ZipStrain Enables Rapid and Precise Strain-Resolved Metagenomics

Ghadermazi, P.; Emerson, J. B.; Olm, M. R.

2026-05-22 bioinformatics
10.64898/2026.05.20.726564 bioRxiv
Show abstract

Strain-resolved metagenomics characterizes microbial communities at nucleotide-level resolution, enabling researchers to differentiate identical from closely related organisms and characterize population structure and gene content variation. Here we introduce ZipStrain, a program that performs highly accurate strain-resolved metagenomics over 500x faster than available methods while offering superior RAM management. Applied to a dataset of 2,754 samples spanning human populations, we identify a strain-sharing gradient across social relationships, reveal striking variation in clonal structure across bacteria and bacteriophage, and pinpoint genes whose nucleotide identity deviates from genome-wide expectations. ZipStrain is distributed as an open-source Python package and accompanying Nextflow pipeline at https://github.com/OlmLab/ZipStrain.

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