OntologyAligner: Ontology-Aligned Retrieval and Hierarchy-Guided Large Language Model Reranking for Biomedical Ontology Normalization

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.

Knowledge Organization Systems like Ontologies and taxonomies are fundamental for structuring scientific knowledge, yet their manual curation presents a persistent bottleneck in knowledge management. While Large Language Models (LLMs) offer a scalable mechanism for automated ontology generation, their capacity to classify complex, domain-specific semantics requires systematic evaluation. In this paper, we assess the performance of five small, open-source LLMs (up to 9 billion parameters) in identifying semantic relationships between biomedical concepts. To support this evaluation, we introduce MeSH-Rel-4K, a dataset comprising 4K semantic relationships extracted from the Medical Subject Headings (MeSH). We analyse three adaptation strategies: standard prompting, Chain-of-Thought prompting, and fine-tuning. While parameter-constrained models traditionally struggle with the nuances of in-context logic, our results reveal that targeted fine-tuning increases the average F1-score by 34.1 percentage points. These results confirm that direct fine-tuning effectively exceeds the reasoning bottlenecks of smaller LLMs, providing an accurate, automated methodology for the construction and evolution of specialised biomedical ontologies.

Linking free-text phenotype descriptions to ontology terms, typically referred to as phenotype annotation, is essential for the cross-study integration of comparative morphological data. This labor intensive process has heavily relied on highly trained human experts, which makes it challenging to scale and thus a key bottleneck. Dahdul et al. (2018) established a Gold Standard (GS) of Entity-Quality (EQ) annotations across seven phylogenetic studies and used it to evaluate three human curators and the Semantic CharaParser NLP tool with ontology-based semantic similarity metrics; they reported that machine-human consistency was significantly lower than inter-curator (human-human) consistency. Here we revisit that benchmark with five frontier hosted LLMs from Anthropic and OpenAI, each operating as an "agentic curator" within a self-contained workspace that supplies the source publication PDF, the same annotation guide used by the original human curators, the four project ontologies (UBERON, PATO, BSPO, GO), and a validation script. Evaluated against the same Gold Standard, every agent fell within the range of inter-curator variability of the three trained human biocurators of the original study; the best performing agents approached but did not reach the best performing human curator. Agents substantially outperformed Semantic CharaParser on all four metrics.