Cenote-Taker 2 Democratizes Virus Discovery and Sequence Annotation

Abstract

Viruses, despite their great abundance and significance in biological systems, remain largely mysterious. Indeed, the vast majority of the perhaps hundreds of millions of viral species on the planet remain undiscovered. Additionally, many viruses deposited in central databases like GenBank and RefSeq are littered with genes annotated as “hypothetical protein” or the equivalent. Cenote-Taker2, a virus discovery and annotation tool available on command line and with a graphical user interface with free high-performance computation access, utilizes highly sensitive models of hallmark virus genes to discover familiar or divergent viral sequences from user-input contigs. Additionally, Cenote-Taker2 uses a flexible set of modules to automatically annotate the sequence features of contigs, providing more gene information than comparable tools. The outputs include readable and interactive genome maps, virome summary tables, and files that can be directly submitted to GenBank. We expect Cenote-Taker2 to facilitate virus discovery, annotation, and expansion of the known virome.

A New Comprehensive Catalog of the Human Virome Reveals Hidden Associations with Chronic Diseases

“…Cenote-Taker 2 27 was used to check contigs for two common end-features of complete viral genomes: terminal direct repeats (suggesting a circular or LTR-bounded viral genome) or inverted terminal repeats (ITRs). Sequences with direct terminal repeats were arbitrarily assumed to represent circular DNA genomes.…”

“…The current study sought to overcome the traditional challenges of sparse viral databases and poor detection of highly divergent viral sequences by using Cenote-Taker 2, a new virus discovery and annotation tool 27 . The pipeline was applied to sequencing data from nearly 6,000 human metagenome samples.…”

A previously undescribed highly prevalent phage identified in a Danish enteric virome catalogue

“…These viral sequences were identi ed by using a combination of homology to known viruses at protein and/or nucleotide level, genome structure (kmer usage and gene content), the presence of viral-speci c genes and VirSorter category [19]. Completeness of viral genomes was assessed by CheckV (v0.6.0) [41] and viral sequences were annotated using CenoteTaker2 (v2.0.1, parameters: --prune_prophage False --enforce_start_codon False --hsuite_tool hhsearch) [35].…”

“…Identi cation and annotation of DEVoC genes CenoteTaker2 (v2.0.1) was used to predict and annotate open reading frames (ORFs) on the viral genomes of the DEVoC [35]. CenoteTaker2 predicts ORFs using a combination of Phanotate [47] and Prodigal [48] in metagenomic mode and annotates the predicted ORFs using HMMER [49], RPSBLAST [50] and HHSEARCH [51] searches against custom viral HMM, CDD, Pfam and PDB databases.…”

“…vConTACT2 [32] or GRAViTy [33]. Finally, the lack of host information and functional annotation of proteins complicates the characterization of the phages and their interactions with bacteria in the gut [34], [35]. The technical di culties of identifying and characterizing viruses are numerous, but nevertheless it is important to make progress in generating human gut virome catalogues and characterizing them to shed light on the viral dark matter.…”