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Few-Shot Classification of C. elegans Developmental Stages via Explainable Hierarchical Hyperbolic Graph Embeddings

Khalid, N.; Elliott, L.; Obafemi-Ajayi, T.; Wunsch, D.; Scharf, A.

2026-06-22 bioinformatics
10.64898/2026.06.21.733631 bioRxiv
Show abstract

Automated, accurate, and fast developmental-stage classification of C. elegans from microscopy-based morphological images is essential for aging research, drug screening, and disease modeling. However, it remains challenging due to morphological similarities between stages and the limited annotated data. In this work, we propose HyperDev, a hyperbolic few-shot learning framework that addresses these limitations by directly encoding developmental hierarchies in the embedding space, unlike conventional Euclidean approaches that treat stages as independent classes. HyperDev uses Poincare ball geometry, combined with a biologically informed developmental prior, to naturally represent stage relationships. We introduce our self-curated C. elegans dataset spanning seven developmental stages (Egg, L1-L4, Adult, Dauer) with extreme class imbalance (6-8 samples per minority class). HyperDev achieves competitive classification accuracy (76.9-88.3%) while providing intrinsic explainability across nine 7-way few-shot evaluation settings. The learned embeddings exhibited strong biological alignment (Pearson r = 0.669, p < 0.001), while significantly outperforming ProtoNet (r = 0.187), MatchingNet (r = 0.235), and RelationNet (r = 0.464). These results establish hyperbolic geometry as a principled approach to explainable few-shot learning in biological imaging, where understanding learned representations is as critical as predictive performance. Clinical RelevanceBy enabling explainable, data-efficient developmental staging from scarce samples, HyperDev supports improved phenotype quantification for aging research, disease modeling, and drug screening.

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