Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

Zheng, W.; Zhao, S.; Yin, Y.; Zhang, H.; Needham, D. M.; Evans, E. D.; Dai, C. L.; Lu, P. J.; Alm, E. J.; Weitz, D. A.

doi:10.1101/2020.12.14.422699

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bioRxiv · 10.1101/2020.12.14.422699

Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

Zheng, W.·Zhao, S.·Yin, Y.·Zhang, H.·Needham, D. M.·Evans, E. D.·Dai, C. L.·Lu, P. J.·Alm, E. J.·Weitz, D. A.

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Abstract

We present Microbe-seq, a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

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Zheng, W., Zhao, S., Yin, Y., Zhang, H., Needham, D. M., Evans, E. D., Dai, C. L., Lu, P. J., Alm, E. J., Weitz, D. A.. 2020-12-14. Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome. https://doi.org/10.1101/2020.12.14.422699

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