BioHiCL: Hierarchical Multi-Label Contrastive Learning for Biomedical Retrieval with MeSH Labels

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.

Retrieval-Augmented Generation (RAG) offers a well-established path to grounding large language model (LLM) outputs in external knowledge, yet the question of which retrieval strategy works best in a high-stakes domain such as biomedicine has not received the controlled, multi-metric treatment it deserves. This paper presents a systematic empirical comparison of five retrieval strategies -- Dense Vector Search, Hybrid BM25 + Dense retrieval, Cross-Encoder Reranking, Multi-Query Expansion, and Maximal Marginal Relevance (MMR) -- within a biomedical question-answering RAG pipeline. All strategies share a fixed generation model (GPT-4o-mini), a common vector store (ChromaDB), and OpenAI's text-embedding-3-small embeddings, ensuring that observed differences are attributable to retrieval alone. Evaluation is conducted on 250 question-answer pairs drawn from a preprocessed subset of the BioASQ benchmark (rag-mini-bioasq) using four DeepEval metrics: contextual precision, contextual recall, faithfulness, and answer relevancy, each reported with 95% confidence intervals. A no-context ablation is included as a lower bound. Cross-Encoder Reranking achieves the best composite score (0.827) and highest contextual precision (0.852), confirming that query-document interaction yields measurable retrieval gains. Multi-Query Expansion, despite its recall-oriented design, produces the weakest contextual precision (0.671), suggesting naive query diversification introduces retrieval noise. MMR sacrifices answer relevancy for diversity, while the Dense baseline (composite 0.822) falls within 0.005 points of the top strategy. All RAG conditions dramatically outperform the no-context ablation on answer relevancy (0.658-0.701 vs. 0.287), confirming the practical value of retrieval. The full pipeline, hyperparameters, and evaluation code are publicly available.

While dense biomedical embeddings achieve strong performance, their opaque dimensions limit transparency in biomedical NLP. Recent question-based interpretable embeddings represent text through binary answers to natural-language questions, but existing approaches rely primarily on corpus-driven signals, often capturing topical or stylistic differences rather than fine-grained biomedical distinctions. We propose QIME, an ontology-grounded framework for interpretable biomedical text embeddings in which each dimension corresponds to an explicit biomedical-domain yes/no question. QIME leverages a biomedical ontology to guide contrastive question generation from semantic clusters, producing atomic, domain-grounded questions. It constructs embeddings via similarity-based semantic activation with MMR-based diversity-aware dimension selection, yielding sparse representations efficiently. Experiments on biomedical clustering, STS and retrieval benchmarks show that QIME consistently outperforms prior interpretable embedding methods and substantially narrows the gap to strong black-box biomedical encoders. It also imposes substantially lower cognitive burden than existing methods, providing concise and domain-specific interpretations. The code is available at https://github.com/L1nzh/QIME.