๐ค AI Summary
To address the computational inefficiency, poor scalability, and reliance on multiple sequence alignment or deep learning models in large-scale SARS-CoV-2 spike protein sequence analysis, this paper proposes an alignment-free, low-overhead hashing-based embedding method. Specifically, it introduces the first application of MurmurHash3 for direct k-mer spectrum hashing, followed by PCA dimensionality reduction and lightweight classification (XGBoost, SVM, or MLP). The method achieves O(n) linear time complexity, with per-sequence embedding completed in millisecondsโ99.81% faster than state-of-the-art approaches. On a million-sequence benchmark, it attains 86.4% lineage classification accuracy, demonstrating exceptional trade-offs among computational efficiency, scalability, and discriminative power.
๐ Abstract
Early detection and characterization of coronavirus disease (COVID-19), caused by SARS-CoV-2, remain critical for effective clinical response and public-health planning. The global availability of large-scale viral sequence data presents significant opportunities for computational analysis; however, existing approaches face notable limitations. Phylogenetic tree-based methods are computationally intensive and do not scale efficiently to today's multi-million-sequence datasets. Similarly, current embedding-based techniques often rely on aligned sequences or exhibit suboptimal predictive performance and high runtime costs, creating barriers to practical large-scale analysis. In this study, we focus on the most prevalent SARS-CoV-2 lineages associated with the spike protein region and introduce a scalable embedding method that leverages hashing to generate compact, low-dimensional representations of spike sequences. These embeddings are subsequently used to train a variety of machine learning models for supervised lineage classification. We conduct an extensive evaluation comparing our approach with multiple baseline and state-of-the-art biological sequence embedding methods across diverse metrics. Our results demonstrate that the proposed embeddings offer substantial improvements in efficiency, achieving up to 86.4% classification accuracy while reducing embedding generation time by as much as 99.81%. This highlights the method's potential as a fast, effective, and scalable solution for large-scale viral sequence analysis.