Generation of lineage-resolved complete metagenome-assembled genomes by precision phasing

• Published in: bioRxiv
• Main Authors: Bickhart, Derek M., Kolmogorov, Mikhail, Tseng, Elizabeth, Portik, Daniel M., Korobeynikov, Anton, Tolstoganov, Ivan, Uritskiy, Gherman, Liachko, Ivan, Sullivan, Shawn T., Shin, Sung Bong, Zorea, Alvah, Andreu, Victòria Pascal, Panke-Buisse, Kevin, Medema, Marnix H., Mizrahi, Itzik, Pevzner, Pavel A., Smith, Timothy P.L.
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 04.05.2021
• Edition: 1.1
• Subjects: Microbiology
• ISSN: 2692-8205
• DOI: 10.1101/2021.05.04.442591

Microbial communities in many environments include distinct lineages of closely related organisms which have proved challenging to separate in metagenomic assembly, preventing generation of complete metagenome-assembled genomes (MAGs). The advent of long and accurate HiFi reads presents a possible means to address this challenge by generating complete MAGs for nearly all sufficiently abundant bacterial genomes in a microbial community. We present a metagenomic HiFi assembly of a complex microbial community from sheep fecal material that resulted in 428 high-quality MAGs from a single sample, the highest resolution achieved with metagenomic deconvolution to date. We applied a computational approach to separate distinct haplotype lineages and identified haplotypes of hundreds of variants across hundreds of kilobases of genomic sequence. Analysis of these haplotypes revealed 220 lineage-resolved complete MAGs, including 44 in single circular contigs, and demonstrated improvement in overall assembly compared to error-prone long reads. We report the characterization of multiple, closely-related microbes within a sample with potential to improve precision in assigning mobile genetic elements to host genomes within complex microbial communities.