MetaTrass: A high-quality metagenome assembler of the human gut microbiome by cobarcoding sequencing reads.

Abstract

Metagenomic evidence of great genetic diversity within the nonconserved regions of the human gut microbial genomes appeals for new methods to elucidate the species-level variability at high resolution. However, current approaches cannot satisfy this methodologically challenge. In this study, we proposed an efficient binning-first-and-assembly-later strategy, named MetaTrass, to recover high-quality species-resolved genomes based on public reference genomes and the single-tube long fragment read (stLFR) technology, which enables cobarcoding. MetaTrass can generate genomes with longer contiguity, higher completeness, and lower contamination than those produced by conventional assembly-first-and-binning-later strategies. From a simulation study on a mock microbial community, MetaTrass showed the potential to improve the contiguity of assembly from kb to Mb without accuracy loss, as compared to other methods based on the next-generation sequencing technology. From four human fecal samples, MetaTrass successfully retrieved 178 high-quality genomes, whereas only 58 ones were provided by the optimal performance of other conventional strategies. Most importantly, these high-quality genomes confirmed the high level of genetic diversity among different samples and unveiled much more. MetaTrass was designed to work with metagenomic reads sequenced by stLFR technology, but is also applicable to other types of cobarcoding libraries. With the high capability of assembling high-quality genomes of metagenomic data sets, MetaTrass seeks to facilitate the study of spatial characters and dynamics of complex microbial communities at enhanced resolution. The open-source code of MetaTrass is available at https://github.com/BGI-Qingdao/MetaTrass.