High-resolution metagenome assembly for modern long reads with myloasm

Long-read metagenome assembly promises complete genomic recovery from microbiomes. However, the complexity of metagenomes poses challenges. Here we present myloasm, a metagenome assembler for modern long reads such as PacBio HiFi and Oxford Nanopore Technologies (ONT) R10.4 long reads. Myloasm uses polymorphic k-mers to construct a high-resolution string graph and then leverages differential abundance for graph simplification. On real-world ONT metagenomes, myloasm assembled three times more complete circular contigs than the next-best assembler. Myloasm can make ONT and HiFi assemblies comparable. For example, on a jointly sequenced gut metagenome, myloasm with ONT assembled more complete circular genomes than any assembler with HiFi. Myloasm also recovers previously inaccessible within-species diversity. Here, we recovered six complete Prevotella copri single-contig genomes from a gut metagenome and eight complete TM7 (Saccharibacteria) contigs with >93% similarity from an oral metagenome. Overall, we show that myloasm outperforms existing long-read metagenome assemblers across a range of environments and modern sequencing technologies.