metaFlye: scalable long-read metagenome assembly using repeat graphs

• Published in: Nature methods Vol. 17; no. 11; pp. 1103 - 1110
• Main Authors: Kolmogorov, Mikhail, Bickhart, Derek M., Behsaz, Bahar, Gurevich, Alexey, Rayko, Mikhail, Shin, Sung Bong, Kuhn, Kristen, Yuan, Jeffrey, Polevikov, Evgeny, Smith, Timothy P. L., Pevzner, Pavel A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2020; Nature Publishing Group
• Subjects: 631/114/2785/2302; 631/326/2565/2142; Algorithms; Animals; Assemblies; Assembling; Assembly; Bacteria; Benchmarking; Bioinformatics; Biological Microscopy; Biological Techniques; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; DNA sequencing; Gastrointestinal Microbiome - genetics; Gene clusters; Genetic aspects; Genome, Bacterial - genetics; Genome, Human - genetics; Genomes; Genomics; Heterogeneity; Humans; Life Sciences; Metagenome - genetics; Metagenomics; Metagenomics - methods; Methods; Microbial colonies; Microbiomes; Microbiota - genetics; Natural products; Nucleotide sequencing; Proteomics; Sequence Analysis, DNA - methods; Sheep; Software; Species Specificity; United States
• ISSN: 1548-7091; 1548-7105; 1548-7105
• DOI: 10.1038/s41592-020-00971-x

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. Long-read metagenomics offers a valuable approach for profiling bacterial communities. This work presents a long-read assembler, metaFlye, that specifically addresses the challenges of assembling metagenomes.