RT Journal Article
SR Electronic
T1 Accurate viral genome reconstruction and host assignment with proximity-ligation sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.14.448389
DO 10.1101/2021.06.14.448389
A1 Gherman Uritskiy
A1 Maximillian Press
A1 Christine Sun
A1 Guillermo Domínguez Huerta
A1 Ahmed A. Zayed
A1 Andrew Wiser
A1 Jonas Grove
A1 Benjamin Auch
A1 Stephen M. Eacker
A1 Shawn Sullivan
A1 Derek M. Bickhart
A1 Timothy P. L. Smith
A1 Matthew B. Sullivan
A1 Ivan Liachko
YR 2021
UL http://biorxiv.org/content/early/2021/06/14/2021.06.14.448389.abstract
AB Viruses play crucial roles in the ecology of microbial communities, yet they remain relatively understudied in their native environments. Despite many advancements in high-throughput whole-genome sequencing (WGS), sequence assembly, and annotation of viruses, the reconstruction of full-length viral genomes directly from metagenomic sequencing is possible only for the most abundant phages and requires long-read sequencing technologies. Additionally, the prediction of their cellular hosts remains difficult from conventional metagenomic sequencing alone. To address these gaps in the field and to accelerate the study of viruses directly in their native microbiomes, we developed an end-to-end bioinformatics platform for viral genome reconstruction and host attribution from metagenomic data using proximity-ligation sequencing (i.e., Hi-C). We demonstrate the capabilities of the platform by recovering and characterizing the metavirome of a variety of metagenomes, including a fecal microbiome that has also been sequenced with accurate long reads, allowing for the assessment and benchmarking of the new methods. The platform can accurately extract numerous near-complete viral genomes even from highly fragmented short-read assemblies and can reliably predict their cellular hosts with minimal false positives. To our knowledge, this is the first software for performing these tasks. Being significantly cheaper than long-read sequencing of comparable depth, the incorporation of proximity-ligation sequencing in microbiome research shows promise to greatly accelerate future advancements in the field.Competing Interest StatementGU, MP, SE, AW, JG, BA, SS, and IL are past or present employees of Phase Genomics. MP is an employee of Inscripta. All other authors have no competing interests.