Virology Journal · 12 authors, 6 centres
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The authors developed MRF (Missing Regions Finder), a bioinformatics tool that identifies missing genome regions and coding sequences in WSSV genomes compared to a reference, addressing annotation inconsistencies across isolates. Using MRF, they cataloged missing coding sequences in WSSV and linked certain genomic features to virulence through phylogenomics, machine learning, and homologous gene analysis.
This study presents MRF, a tool combining the mummer alignment tool with custom scripts to identify missing genome regions and coding sequences (CDS) in virus genomes relative to a reference. Implemented as both a web tool and command-line interface, MRF was applied to WSSV, the largest known animal DNA virus, which has variable genome lengths and inconsistent annotation nomenclature across isolates. Using WSSV-CN (AF332093) as the reference, the authors documented missing CDS, deletion hotspots, and linked findings to virulence using phylogenomics, machine learning models, and homologous gene analysis. They found that ubiquitination, transcription regulation, and nucleotide metabolism may be important for WSSV pathogenesis, while structural proteins VP19, VP26, and VP28 are essential for virus assembly. The average nucleotide identity between any two WSSV isolates exceeds 98%, yet genome length varies considerably. A noted limitation is that MRF may report inflated missing genome lengths for genomic regions shorter than the exact match length. The tool complements similarity-based approaches like BLAST for comparative genomics of large, highly similar, length-varying viral genomes.
