Identification and Characterization of Novel Metagenome Assembled Uncultivated Virus Genomes from Human Gut

Abstract

Metagenomics has revealed an unprecedented viral diversity in human gut although, most of the sequence data remains to be characterized. In this study, we mined a collection of 1090 metagenome assembled "high quality" genomes of human gut viruses. Sequence analysis has revealed eight new species from seven genera of the class, Caudoviricetes and nineteen new species from fourteen genera of the ssDNA virus family, Microviridae. In addition, four "high quality" genomes were identified, which do not show similarity to sequences present in any of the four major viral databases, NCBI viral RefSeq, IMG-VR, Gut Phage Database (GPD) and Gut Virome Database (GVD). Further, annotation of the "high-quality" genomes and KEGG pathway analysis has identified antB, dnaB, DNMT1, DUT, xlyAB, xtmB and xtmA as the most widespread viral and Auxiliary Metabolic Genes (AMGs). Genes for virulence, host-takeover, drug resistance, tRNA, tmRNA and CRISPR elements were also found. Bacterial hosts are predicted for around 40% of the analyzed genomes. Overall, we report identification of new viral genomes and genome analyses of human gut viruses, which will be useful for biological characterization to establish their significance in physiology. IMPORTANCEMultiple studies have found that dysbiosis of gut virome is associated with conditions such as metabolic syndromes, autoimmune disorders and infectious diseases. In the interest of its therapeutic and diagnostic potential, intestinal virome warrants detailed investigation. However, limited ability to culture gut viruses becomes one of the challenges for their biological characterization and fully understanding their role in physiology. Sequence analysis and host prediction methods provide opportunities to understand gut viruses, their functional potential and devise ways for further characterization.