GenEx: A Graph-Based Representational Paradigm for SARS-CoV-2 Variant Detection via Codon Co-occurrence Networks

Abstract

Genomic analysis on viruses such as SARS-CoV-2 variants: Beta, Gamma, Delta, and Omicron is heavily dominated by classical bioinformatics methods, including Sequence Alignment, Phylogenetic Analysis, and Mutation Frequency Statistics. These approaches use pairwise codon or nucleotide distance matrices to analyze gene sequences, treating them as linear strings rather than capturing their complex contextual interdependencies. We proposed GenEx, a pipeline that converts raw gene sequences into codon co-occurrence graphs and extracts more than 25 graph features. Our two most prominent techniques for graph generation and feature extraction are MSCG (Multi-Scale Codon Co-occurrence Graph) and LAPCG (Linear-time Adjacency PMI Codon Graph). Using these algorithms, we treated codon sequences as structured symbolic vocabularies interpretable to codon co-occurrence graph analysis, a representational paradigm borrowed from computational linguistics. Another major contribution includes implementing a spectral graph feature extraction using Singular Value Decomposition (SVD), using the squared singular value ($\sigma^2$) instead of the traditionally used eigenvalue, which helped us to amplify the separation between dominant and subdominant spectral components, thereby enhancing inter-class separability in downstream classification. And to further demonstrate that our method works, we trained 23 benchmarked ML models against the latest SARS-CoV-2 variants, achieving remarkable results in detecting all SARS-CoV-2 variants.