Few-Shot Biomedical Relation Extraction with Large Language Models: A Viable Alternative to Supervised Learning?

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.

Automatic prompt optimization is still underexplored for episodic few-shot relation extraction with smaller language models. We propose a two-stage framework that combines reasoning-based prompt optimization with gradient-based prompt optimization. The first stage can use any reasoning-based optimizer to make broadprompt improvements in natural language. The second stage applies our GradPO, which uses loss and gradient signals to identify high-impact prompt spans and refine them with local edits. Experiments on FS-TACRED and FS-FewRel show that local refinement usually improves prompts found by the first stage, and GradPO is the most consistent refiner. Our framework achieves state-of-the-art performance on FS-TACRED with Qwen3-4B and remains competitive on FS-FewRel.

Relation extraction (RE) for low-resource languages is typically constrained by the lack of annotated corpora. We investigate the feasibility of cross-lingual RE for Romanian by combining automatic dataset translation with large language model (LLM) inference. We translate the SemEval-2010 Task 8 benchmark from English to Romanian using an LLM-based translation pipeline and evaluate Gemma 4 31B under zero-shot, few-shot, and QLoRA fine-tuned configurations, against four encoder baselines spanning 125M to 560M parameters: XLM- RoBERTa (base and large), Romanian BERT, and RoBERT- large. We assess two task formulations: relation classification with marked entities and end-to-end extraction. Our results show that Romanian incurs a 3 to 5 percentage point (pp) drop relative to English in prompt-only settings, that few-shot prompting provides marginal gains over zero-shot, and that QLoRA fine-tuning improves macro F1-Score by more than 22 percentage points in both languages while reducing the cross-lingual gap from 3.3 to 1.4pp. The encoder baselines come within 1-4pp of QLoRA Gemma on Romanian despite being 50-250 times smaller, with monolingual Romanian BERT at 125M parameters matching multilingual XLM-R at 278M. The case for using a 31B model for single-task RE on Romanian is therefore weak in deployment scenarios where compute matters. We release the translated dataset, evaluation code, and trained models.