Genome-resolved metagenomics using short-, long-read and metaHiC sequencing

Reference-quality metagenome-assembled genomes (MAGs) are the key to exploring microbial compositions and microbe-phenotype associations. They can be recovered by different sequencing technologies and computational tools, which need an unbiased and comprehensive assessment to identify best practices. This work systematically evaluates 40 distinct strategies to recover high-quality MAGs generated by eight assemblers, eight metagenomics binners, and four sequencing technologies, including short-, long-read and metaHiC sequencing. We notice that the hybrid assemblies of short- and long-reads outperform either short- or long-read assemblies and generate more contigs with high contiguity. When the hybrid assemblies are combined with metaHiC-based binning (Hybrid-HiC), more high-quality MAGs with higher taxonomic diversity are recovered, and more tRNA and rRNA genes, phages, plasmids and antibiotic resistance genes are identified in the mock, simulated and real datasets.