Craft: a machine learning approach to dengue subtyping.

Motivation: The dengue virus poses a major global health threat, with nearly 390 million infections annually. A recently proposed hierarchical dengue nomenclature system enhances spatial resolution by defining major and minor lineages within genotypes, aiding efforts to track viral evolution. While current subtyping tools-Genome Detective, GLUE, and Nextclade-rely on computationally intensive sequence alignment and phylogenetic inference, machine learning presents a promising alternative for achieving accurate and rapid classification. Results: We present Craft (Chaos Random Forest), a machine learning framework for dengue subtyping. We demonstrate that Craft is capable of faster classification speeds while matching or surpassing the accuracy of existing tools. Craft achieves 99.5% accuracy on a hold-out test set formed from a consensus of predictions from existing tools and processes over 140 000 sequences per minute. Notably, Craft maintains remarkably high accuracy even when classifying sequence segments as short as 700 nucleotides. Availability and implementation: Source code is available at: https://github.com/INFORM-Africa/AI-viral-lineage-classification.