FLAVi‐Web: A Web Annotator for Viral Genomes of Flaviviridae with a Revised Phylogeny of the Family

Abstract

The ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and zika, demand a greater understanding of how these viruses evolve, emerge and spread in order to respond. Central to this understanding is an updated phylogeny of the entire family. Accurate gene annotations are pivotal to allow researchers to question how the fundamental genetic elements for these viruses evolve and function knowing they are comparing homologous genomic regions. To tackle these problems, our team has published a pipeline called FLAVi ("Fast Loci Annotation of Viruses"), an annotation pipeline for Flaviviridae that uses a combination of ab initio and homology‐based strategies. The pipeline recovered 100% of the genes in reference genomes and annotated over 97% of the expected genes in the remaining noncurated sequences. It was also further demonstrated that the combined analysis of genomes of all genera of Flaviviridae (Flavivirus, Hepacivirus, Pegivirus, and Pestivirus), as made possible by this annotation strategy, improves the phylogenetic analyses of these viruses for all optimality criteria that were tested (parsimony, maximum likelihood, and posterior probability). Here, we propose a user‐friendly web‐based application version of FLAVi, FLAVi‐Web (available at flavi‐web.com). FLAVi‐Web was created using Flask (Grinberg, 2018), a Python‐based application for the creation of web interfaces. Flask uses HTML and JavaScript to create the aesthetic properties of the web interface. The web application takes as input a FASTA file with the pathogen genomic information and outputs a compressed file with the main annotation results in a GFF3 file format. This novel web implementation enhances our ability to maintain and improve the FLAVi pipeline over time, ultimately promoting its usage among the virology community. Left ‐ Homepage of flavi‐web. com, Right ‐ Flowchart describing the application pipeline.