FLAVi: An Enhanced Annotator for Viral Genomes of Flaviviridae

Abstract

Responding to the ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and Zika, demands a greater understanding of how these viruses emerge and spread. Updated phylogenies are central to this understanding. Most cladograms of Flaviviridae focus on specific lineages and ignore outgroups, hampering the efficacy of the analysis to test ingroup monophyly and relationships. This is due to the lack of annotated Flaviviridae genomes, which has gene content variation among genera. This variation makes analysis without partitioning difficult. Therefore, we developed an annotation pipeline for the genera of Flaviviridae (Flavirirus, Hepacivirus, Pegivirus, and Pestivirus, named “Fast Loci Annotation of Viruses” (FLAVi; http://flavi-web.com/), that combines ab initio and homology-based strategies. FLAVi recovered 100% of the genes in Flavivirus and Hepacivirus genomes. In Pegivirus and Pestivirus, annotation efficiency was 100% except for one partition each. There were no false positives. The combined phylogenetic analysis of multiple genes made possible by annotation has clear impacts over the tree topology compared to phylogenies that we inferred without outgroups or data partitioning. The final tree is largely congruent with previous hypotheses and adds evidence supporting the close phylogenetic relationship between dengue and Zika.

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

“…We found that the three fluoroquinolones used in this study, enoxacin, ciprofloxacin and difloxacin, all suppressed replication of the six flaviviruses tested at low micromolar concentrations, with the exception that difloxacin lacked potency for MODV. These six flaviviruses, DENV-1, DENV-2, DENV-4, ZIKV, LGTV, and MODV, span the diversity of human pathogenic flaviviruses [68,69]. Enoxacin consistently demonstrated the lowest EC 50 values.…”

Fundamental evolution of all Orthocoronavirinae including three deadly lineages descendent from Chiroptera‐hosted coronaviruses: SARS‐CoV, MERS‐CoV and SARS‐CoV‐2

“…Lam et al, 2020;Xiao et al, 2020; coronaviruses as the sister group of SARS-COV-2. These papers often suffer from the lack of diversity of genes and hosts sampled, both of which can impact the estimation of ingroup relationships (Schneider et al, 2020;Wenzel, 2020). In our manuscript, we overcome these shortcomings in phylogenetic analyses of coronaviruses by including as much data from the coronaviruses as possible to determine orthology and performing simultaneous analysis of a comprehensive sample of the Orthocoronavirinae subfamily including its four genera (i.e.…”

“…The mixed results from TREETIME experiments underscore the importance of more research and development into gene annotation and data partitioning for phylogenetic systematics and translational work that depends on phylogenetics. For additional discussion on the importance of gene annotation and outgroup sampling in viral phylogenomics, see Schneider et al (2020).…”

Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype

“…“ The SH-aLRT is an approximation of the likelihood ratio, a direct measure of how much the evidence supports the hypothesis. SH-aLRT is an approximation of the ratio of the log-likelihood of the optimal hypothesis and the best contradictory hypothesis ” (Schneider et al, 2020 ).…”