An ensemble strategy that significantly improves de novo assembly of microbial genomes from metagenomic next-generation sequencing data

作者:Deng Xutao*; Naccache Samia N; Ng Terry; Federman Scot; Li Linlin; Chiu Charles Y; Delwart Eric L
来源:Nucleic Acids Research, 2015, 43(7): e46.
DOI:10.1093/nar/gkv002

摘要

Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free (de novo) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.

  • 出版日期2015-4-20