- Kolmogorov, Mikhail;
- Bickhart, Derek;
- Behsaz, Bahar;
- Gurevich, Alexey;
- Rayko, Mikhail;
- Shin, Sung;
- Kuhn, Kristen;
- Yuan, Jeffrey;
- Polevikov, Evgeny;
- Smith, Timothy;
- Pevzner, Pavel
Long-read sequencing technologies have substantially improved the assemblies of many isolate bacterial genomes as compared to fragmented short-read assemblies. However, assembling complex metagenomic datasets remains difficult even for state-of-the-art long-read assemblers. Here we present metaFlye, which addresses important long-read metagenomic assembly challenges, such as uneven bacterial composition and intra-species heterogeneity. First, we benchmarked metaFlye using simulated and mock bacterial communities and show that it consistently produces assemblies with better completeness and contiguity than state-of-the-art long-read assemblers. Second, we performed long-read sequencing of the sheep microbiome and applied metaFlye to reconstruct 63 complete or nearly complete bacterial genomes within single contigs. Finally, we show that long-read assembly of human microbiomes enables the discovery of full-length biosynthetic gene clusters that encode biomedically important natural products.