Asking the Right Questions: Ontology-Grounded Interpretable Embeddings for Biomedical Text

We introduce OntologyBench, a tiered biomedical retrieval benchmark comprising 471,854 training and 125,744 evaluation query-document relevance pairs across concept grounding, relational retrieval, and compositional phenotype-based retrieval. Although these tasks can be tractable using ontology-aware reference methods, across task tiers, embedding performance is generally lower on relational and compositional tasks than on concept-grounding tasks. Fine-tuning on ontology-derived supervision improves performance on several relational and compositional tasks, whereas the evaluated reranking and LLM-based candidate-scoring methods provide little or no end-to-end improvement. Errors frequently reflect diseases matching only subsets of the phenotype evidence. These findings indicate that the evaluated embedding and reranking configurations do not reliably recover the compatibility encoded by the selected ontology relations and phenotype combinations and motivate retrieval systems that better integrate learned representations with structured biomedical knowledge.

Effective biomedical information retrieval requires modeling domain semantics and hierarchical relationships among biomedical texts. Existing biomedical generative retrievers build on coarse binary relevance signals, limiting their ability to capture semantic overlap. We propose BioHiCL (Biomedical Retrieval with Hierarchical Multi-Label Contrastive Learning), which leverages hierarchical MeSH annotations to provide structured supervision for multi-label contrastive learning. Our models, BioHiCL-Base (0.1B) and BioHiCL-Large (0.3B), achieve promising performance on biomedical retrieval, sentence similarity, and question answering tasks, while remaining computationally efficient for deployment.

Biomedical question answering with large language models is commonly evaluated using answer accuracy, but answer accuracy alone does not indicate whether a model can produce parseable outputs, follow structured reliability instructions, recognize weak answer spaces, or avoid confident incorrect commitments. This paper presents HypothesisMed, an inference-time reliability pipeline for biomedical multiple-choice question answering. It combines direct, chain-of-thought, HypothesisMed-v3 prompting, and answer fusion. The final answer is selected by fusion, while HypothesisMed-v3 supplies SPACE labels and confidence information. SPACE labels mark the answer space as VALID, INCOMPLETE, or CONTRADICTED. We evaluate Qwen2.5-7B, Phi-4-mini, DeepSeek-R1-32B, and BioMistral-7B on MedQA, MedMCQA, and PubMedQA using 1,000 examples per dataset. The pipeline improves weighted accuracy over each model's best direct or chain-of-thought baseline while increasing parse and SPACE coverage. We also scale evaluation to Qwen2.5-7B and Phi-4-mini using 10,183 examples per model. Fusion improves Phi-4-mini accuracy from 0.4296 to 0.5192, while Qwen2.5-7B chain-of-thought remains slightly higher in answer accuracy. However, Qwen2.5-7B fusion achieves complete parse and SPACE coverage with much lower false commitment. A 12,000-example SPACE stress test shows answer-space diagnosis remains difficult, with SPACE accuracy of 0.3074 for Qwen2.5-7B and 0.4168 for Phi-4-mini. These results show that answer accuracy, parseability, structured reliability reporting, calibration behavior, and false-commitment behavior are separable capabilities. The main contribution is not a universal state-of-the-art claim, but a reproducible inference-time framework for evaluating biomedical question answering models as auditable workflow components under structured reliability constraints.