HyperTaxa: Multiscale Genome Representations for Generalized Microbial Taxonomic Inference

Overview & Synopsis

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 multiscale transition encoding and taxonomy-aware alignment are key contributors to generalization. These results position HyperTaxa as a complementary taxonomy-aware representation and candidate-generation framework for microbial identification under incomplete reference coverage and open-set uncertainty.