VICAST: An Integrated Toolkit for Viral Genome Annotation Curation and Low-Frequency Variant Analysis in Passage...

Area of Science:

• Virology
• Genomics
• Bioinformatics

Background:

• Cultured virus passage studies are crucial for understanding viral evolution and host adaptation.
• Analyzing genomic changes requires accurate genome annotation and sensitive detection of low-frequency variants.
• Existing tools often address annotation and variant calling separately, with limitations for novel or poorly annotated genomes.

Purpose of the Study:

• To develop an integrated software suite, VICAST, for comprehensive analysis of viral genomes in passage studies.
• To combine semi-automated genome annotation with manual curation and low-frequency variant calling.
• To provide a versatile tool capable of handling diverse viral genome structures and annotation qualities.

Main Methods:

• VICAST integrates semi-automated genome annotation with manual curation checkpoints and low-frequency variant calling.
• It offers four annotation pathways for polyproteins, unannotated, and multi-segmented genomes.
• The toolkit integrates with SnpEff for functional variant annotation and includes a module for haplotype validation.

Main Results:

• VICAST was validated on SARS-CoV-2, Dengue virus 2, and Influenza A H1N1 datasets, demonstrating its versatility.
• It produced novel, validated annotations for Chikungunya virus, incorporated into a custom SnpEff database.
• VICAST showed significant advantages over VADR, being 5.6-8.1 times faster and including contamination screening.

Conclusions:

• VICAST provides an integrated and efficient solution for analyzing viral genomic changes in passage studies.
• Its flexible annotation and sensitive variant detection capabilities advance the study of viral evolution.
• The software offers improved performance and novel annotation resources for the research community.