Hecatomb: An End-to-End Research Platform for Viral Metagenomics

1 Background: Analysis of viral diversity using modern sequencing technologies offers 2 extraordinary opportunities for discovery. However, these analyses present a number of 3 bioinformatic challenges due to viral genetic diversity and virome complexity. Due to the 4 lack of conserved marker sequences, metagenomic detection of viral sequences requires 5 a non-targeted, random (shotgun) approach. Annotation and enumeration of viral 6 sequences relies on rigorous quality control and effective search strategies against 7 appropriate reference databases. Virome analysis also benefits from the analysis of both 8 individual metagenomic sequences as well as assembled contigs. Combined, virome 9 analysis results in large amounts of data requiring sophisticated visualization and 10 statistical tools. 11 Results: Here we introduce Hecatomb, a bioinformatics platform enabling both read and 12 contig based analysis. Hecatomb integrates query information from both amino acid and 13 nucleotide reference sequence databases. Hecatomb integrates data collected 14 throughout the workflow enabling analyst driven virome analysis and discovery. 15 Hecatomb is available on GitHub at https://github.com/shandley/hecatomb. 16 Conclusions: Hecatomb provides a single, modular software solution to the complex tasks required of many virome analysis. We demonstrate the value of the approach by applying Hecatomb to both a host-associated (enteric) and an environmental (marine) virome data set. Hecatomb provided data to determine true- or false-positive viral sequences in both data sets and revealed complex virome structure at distinct marine 21 reef sites.