HyperTaxa: Multiscale Genome Representations for Generalized Microbial Taxonomic Inference

Akash Rao, Sushim Gupta, Vishalini Ramnath, Akhilesh Ramachandran, Sathyanarayanan Aakur

Reliable microbial taxonomic inference is challenged by the rapid growth of newly sequenced organisms and incomplete reference coverage. While alignment- and database-driven tools remain essential for reference-backed identification, they are not designed for learned inference over species absent from genome-level training. We introduce HyperTaxa, a taxonomy-aligned representation learning framework for open-set microbial taxonomic inference. HyperTaxa encodes whole genomes as multiscale hyperspectral k-mer transition fields and aligns these representations to a taxonomy-derived semantic space using a two-stage Node2Vec-to-MDS procedure that combines local graph structure with global hierarchical distance preservation. The resulting space supports zero-shot inference over species excluded from genome-level training but represented in the taxonomy, generalized zero-shot inference over seen and unseen species, and cascaded genus-to-species prediction. Across benchmark and large-scale disjoint-species evaluations, HyperTaxa improves taxonomic prediction over pseudo-image and transformer-graph baselines, with the strongest gains at higher taxonomic ranks. Ablations further show that…