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Nat Biotechnol. 2016 Jan;34(1):64-9. doi: 10.1038/nbt.3416. Epub 2015 Dec 14.

Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome.

Author information

1
Department of Computer Science, Stanford University, Stanford, California, USA.
2
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Abstract

Identifying bacterial strains in metagenome and microbiome samples using computational analyses of short-read sequences remains a difficult problem. Here, we present an analysis of a human gut microbiome using TruSeq synthetic long reads combined with computational tools for metagenomic long-read assembly, variant calling and haplotyping (Nanoscope and Lens). Our analysis identifies 178 bacterial species, of which 51 were not found using shotgun reads alone. We recover bacterial contigs that comprise multiple operons, including 22 contigs of >1 Mbp. Furthermore, we observe extensive intraspecies variation within microbial strains in the form of haplotypes that span up to hundreds of Kbp. Incorporation of synthetic long-read sequencing technology with standard short-read approaches enables more precise and comprehensive analyses of metagenomic samples.

PMID:
26655498
PMCID:
PMC4884093
DOI:
10.1038/nbt.3416
[Indexed for MEDLINE]
Free PMC Article

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