Reference-guided Assembly of Metagenomic Sequences

Metagenomic studies have primarily relied on de novo approaches for reconstructing genes and genomes from microbial mixtures. While database driven approaches have been employed in certain analyses, they have not been used in the assembly of metagenomic data. This is in part due to the small size and biased coverage of public genome databases, but also due to the inherent computational cost of mapping tens of millions of reads to thousands of full genome sequences. Here we describe the first effective approach for reference-guided metagenomic assembly that can complement and improve upon de novo metagenomic assembly methods. Combined with de novo assembly approaches, we show that MetaCompass is able to generate significantly better results than can be obtained by either comparative or de novo assembly independently. Using this approach we report improved assemblies for 688 metagenomic samples from the Human Microbiome Project.