Organizations: School of Information Sciences, University of Illinois Urbana-Champaign, 501 E Daniel St., Champaign, 61820, IL, USA · Division of Computational Health Sciences, Department of Surgery, University of Minnesota, 516 Delaware St SE, Minneapolis, 55455, MN, USA
Abstract
Biomedical relation extraction (BioRE) extracts structured knowledge from biomedical literature for applications such as knowledge base construction and hypothesis generation. Traditional symbolic systems such as SemRep provide high precision but limited recall, while large language models (LLMs) offer stronger contextual reasoning but remain prone to false-positive predictions. We developed ANCHOR-RE, a framework that integrates ontology-guided reasoning, external knowledge grounding, and data-driven verification rules into LLM inference. We evaluated it on three BioRE benchmarks (SemRepGS, DDI, and ChemProt) using both proprietary and open-weight LLMs. To assess generalizability beyond benchmark datasets while reducing potential evaluation bias from LLM pretraining contamination, we conducted a temporal evaluation using 100 biomedical articles published in 2026. With the proprietary backbone, ANCHOR-RE outperformed direct LLM prompting, improving micro-F1 from 0.654 to 0.676 on SemRepGS, from 0.769 to 0.872 on DDI, and from 0.939 to 0.941 on ChemProt. On DDI and ChemProt, it also outperformed previously reported inference-only methods and approached fine-tuned or instruction-tuned systems without parameter updates. Similar performance gains observed with open-weight LLMs indicate that the benefits were not limited to the proprietary backbone. On the post-cutoff set, manual assessment of 500 randomly sampled predictions yielded a precision of 69%, maintaining consistent precision on previously unseen biomedical literature. Neuro-symbolic reasoning can improve the reliability of LLM-based BioRE without fine-tuning. Results across multiple benchmarks, model families, and post-cutoff literature support ANCHOR-RE as a practical training-free approach to biomedical literature mining.
Biomedical relation extraction (BioRE) is a key step in transforming biomedical literature into structured knowledge. However, most existing approaches rely on supervised models trained on costly annotated datasets, limiting their scalability and adaptability across relation types and domains. We investigate few-shot BioRE using prompt-based learning with large language models (LLMs) and compare two task formulations: pairwise classification, which predicts relations for individual entity pairs, and joint generation, which extracts multiple relations in a single model call. Experiments on the BioREDirect dataset reveal a clear precision-recall trade-off. Pairwise classification achieves higher recall, whereas joint generation is more precise and computationally efficient. The best-performing model achieves a micro-F1 score of 0.44, substantially outperforming previous few-shot results (0.34) while remaining below the supervised baseline (0.56). Much of this gap is attributable to a single ambiguously defined relation type. When evaluated using macro-F1, which better captures performance across relation types in an imbalanced setting, prompt-based approaches outperform the supervised baseline (0.45 vs. 0.38), particularly on rare relation types. These findings highlight the potential of LLMs for BioRE in low-resource settings and underscore the importance of well-defined relation schemas.
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.