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Benchmarking large language models for biomedical natural language processing applications and recommendations
Open accessAbstract
The rapid growth of biomedical literature poses challenges for manual knowledge curation and synthesis. Biomedical Natural Language Processing (BioNLP) automates the process. While Large Language Models (LLMs) have shown promise in general domains, their effectiveness in BioNLP tasks remains unclear due to limited benchmarks and practical guidelines. We perform a systematic evaluation of four LLMs—GPT and LLaMA representatives—on 12 BioNLP benchmarks across six applications. We compare their zero-shot, few-shot, and fine-tuning performance with the traditional fine-tuning of BERT or BART models. We examine inconsistencies, missing information, hallucinations, and perform cost analysis. Here, we show that traditional fine-tuning outperforms zero- or few-shot LLMs in most tasks. However, closed-source LLMs like GPT-4 excel in reasoning-related tasks such as medical question answering. Open-source LLMs still require fine-tuning to close performance gaps. We find issues like missing information and hallucinations in LLM outputs. These results offer practical insights for applying LLMs in BioNLP.
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“Our extensive prior work comparing zero/few-shot and fine-tuned LLaMA models have demonstrated the superior performance of fine-tuned models51–54.”
From Social determinants of health extraction from clinical notes across institutions using large language models (2025) · cites this paper as [54]
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Mesinovic, M., Buhlan, M., & Zhu, T. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01742-3 · Cited by 8
“…biomedical natural language processing tasks demonstrates that while LLMs excel at reasoning-intensive question answering, they under-perform fine-tuned domain-specific models in information extraction, with qualitative analyses revealing prevalent missing information and inconsistent outputs [84].”
Syahputri, I. W., Budiardjo, E. K., & Putra, P. H. H. (2025) · Applied Informatics · doi:10.3390/ai6090206 · Cited by 9
Entry-level guide to the use of large language models for medical researchPreprint
Jin, Q., Wan, N., Leaman, R., Tian, S., Wang, Z.-Z., Yang, Y.-F., Wang, Z., Xiong, G.-Z., Lai, P.-T., Zhu, Q.-Q., et al. (2024) · PubMed · doi:10.48550/arxiv.2410.18856 · Cited by 9
“For example, LLMs are better for tasks that require medical knowledge and clinical reasoning, but do not often outperform fine-tuned BERT models 63 in simpler tasks such as structurization 64 .”
Self-citationEnhancing Large Language Models with Domain-specific Retrieval Augment Generation
Gilson, A., Ai, X.-G., Arunachalam, T., Chen, Z., Cheong, K. X., Dave, A. D., Duic, C., Kibe, M., Kaminaka, A., Prasad, M., et al. (2024) · arXiv.org · doi:10.48550/arxiv.2409.13902 · Cited by 9
Self-citationDong, Y., Zhang, Z., Zhi, Y., Li, X., Guo, T., He, L., Zhao, S., Yang, X., Tang, J. T., Zhong, W., et al. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101579 · Cited by 12
Multi-Modal Topology-Aware Graph Neural Network for Robust Chemical–Protein Interaction Prediction
Wang, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178666 · Cited by 11
Shao, C., Snyder, D., Li, C., Gu, B., Ngan, K., Yang, C.-T., Wu, J., Wyss, R., Lin, K., & Yang, J. (2025) · Journal of Clinical Epidemiology · doi:10.48550/arxiv.2506.11137 · Cited by 8
“- Macro Precision - Macro Recall - Macro F1”
OpenAI ChatGPT: A Potential Medical Application
Chaddad, A., Jiang, Y., & He, C. (2023) · IEEE International Conference on e-Health Networking, Applications and Services (Healthcom) · doi:10.1109/healthcom56612.2023.10472387 · Cited by 9
“…American College of Gastroenterology Self-Assessment Tests [18] 65.1% 62.4% PSITE 2021 Exam [19] 51.2% 75.3% PubMedQA [20] 51.6% 80.4% NCBI-disease [16] 24.05% 56.73% MedMCQA [13] 50.08% 73.42% SANS ABNS Self-Assessment Exam [21] 73.4% 83.4% BC5CDR: BioCreative V CDR; SCE: Specialty Certificate…”
InfluentialEmerging trends of recommender system for e-commerce: a comprehensive review
Rajpoot, C. S., Tiwari, V., & Vishwakarma, S. K. (2026) · Discover Computing · doi:10.1007/s10791-026-09923-z · Cited by 7
“Text summarization techniques–both extractive and abstractive address this issue by condensing large volumes of textual data into concise, meaningful summaries that retain essential semantic information [119].”
Ghosh, A., Jain, R., Jhangra, A., Saha, S., & Jatowt, A. (2025) · Wiley Interdisciplinary Reviews Data Mining and Knowledge Discovery · doi:10.1002/widm.70045 · Cited by 5
“…RoBERTa for entailment and CUI linking was reported, which propagates into higher downstream ROUGE when these representations seed the summarizer (Chen et al. 2025 (Sundrelingam et al. 2025) processes each note in about 0.5 s and posts an F1 of 0.90 on both Canadian and n2c2 discharge-summary…”
InfluentialSholehrasa, H., Ghanaatian, A., Caragea, D., Tell, L. A., Riviere, J. E., & Jaberi-Douraki, M. (2025) · IEEE International Conference on Tools with Artificial Intelligence · doi:10.1109/ictai66417.2025.00051 · Cited by 7
“1, Step 8) using a 5-shot prompting [33] (Fig.”
Benchmarking GPT-5 for biomedical natural language processingPreprint
Hou, Y., Zhan, Z.-F., Zeng, M., Wu, Y.-F., Zhou, S., & Zhang, R. (2025) · arXiv.org · doi:10.48550/arxiv.2509.04462 · Cited by 7
“5, and LLaMA-2-13B across five text-based task families originally benchmarked by Chen et al. 16 : named entity recognition (NER), relation extraction (RE), multi-label document classification, text summarization, and text simplification.”
InfluentialSelf-citationChen, H., Alfred, M. C., & Cohen, E. (2025) · JMIR Medical Informatics · doi:10.2196/68955 · Cited by 13
“While our findings highlight the promise of open-source LLMs in data-scarce settings, the exclusion of proprietary models limits the generalizability of our findings.”
Adam, T. J., Abosabie, S. A., Dittmer, M., Wolf, E., Abosabie, S. A., Behnke, C., Baier, F., Weickmann, A., Köser, L., Correll, C. U., et al. (2026) · Research Synthesis Methods · doi:10.1017/rsm.2026.10093 · Cited by 8
Huang, X., Xiao, M., Qin, C., Long, Q., Chen, J., Zhou, Y., & Zhu, H. (2026) · ACM SIGKDD Conference on Knowledge Discovery and Data Mining (KDD) · doi:10.1145/3770855.3817489 · Cited by 3
Latency-Aware Benchmarking of Large Language Models for Natural-Language Robot Navigation in ROS 2
Das, M., Hussain, Z., & Nawaz, M. (2026) · Sensors · doi:10.3390/s26020608 · Cited by 5
“This metric is relevant for large-scale or cost-sensitive deployments [21]. https://doi.org/10.3390/s26020608 2.7.”
InfluentialApplication and Prospects of Large Language Models in Small-Molecule Drug Discovery
Ma, J., Liu, J., Xu, D., Song, X., & Zhang, Z. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c04083 · Cited by 9
Zhan, Z.-F., Zhou, S., Zeng, M., Yu, K., Song, M.-J., Chen, X., Wang, J., Hou, Y., & Zhang, R. (2025) · arXiv.org · doi:10.48550/arxiv.2509.04534 · Cited by 6
Self-citationLi, X., Zhao, D., Meng, J., & Lin, H. (2025) · Expert Systems with Applications · doi:10.1016/j.eswa.2025.128342 · Cited by 5
LLM-Based Agents for Competitive Landscape Mapping in Drug Asset Due Diligence
Vinogradova, A., Vinogradov, V., Radkevich, D., Yasny, I., Kobyzev, D., Izmailov, I., Yanchanka, K., Doronin, R., & Doronichev, A. (2025) · arXiv.org · doi:10.48550/arxiv.2508.16571 · Cited by 6
“Moreover, recent studies report that general-purpose, frontier LLMs can be competitive with—or even outperform—task-specific fine-tuned models on certain pharma-adjacent evaluations (Chen et al. 2025; McDuff et al. 2025).”
Yu, J., Tang, Y., Feng, K., Liang, L., Zhang, Q., Ding, K., & Chen, H. (2026) · Scientific Data · doi:10.1038/s41597-026-06594-9 · Cited by 6
“Existing LLM benchmarks in scientific domains (Chen et al., 2025; Sun et al., 2024; Feng et al., 2024; Saikh et al., 2022; Pedersen et al., 2020; Rubungo et al., 2024; Jiang et al., 2025) primarily focus on direct question-answering tasks, offering limited insight into how well LLMs perform in…”
Sarol, M. J., Hong, G., Guerra, E., & Halil Kilicoglu, B. (2024) · Database · doi:10.1093/database/baae079 · Cited by 6
Liu, Z., Liu, S., Yan, W., Song, P., Song, Y., & Gao, R. (2026) · International World Wide Web Conference (WWW) · doi:10.1145/3774904.3792577 · Cited by 2
Yu, S., Cho, E.-J., Kim, S., Park, K., Kim, M.-S., Oh, Y., & Ryu, H. (2026) · Int. J. Medical Informatics · doi:10.1016/j.ijmedinf.2026.106270 · Cited by 5
Zeng, H., Liu, G., Liu, W., Zou, S.-Y., Chen, B., Yang, R., Lin, F., Peng, J., Gao, Y., & Hao, L. (2025) · Public Health · doi:10.1016/j.puhe.2025.106042 · Cited by 5
Self-citationDual-LLM Adversarial Framework for Information Extraction from Research Literature
Li, Z., Yu, Y., Gu, W.-H., Zhu, T.-T., Song, H., Guo, W.-B., Yang, X., & Zhu, Z.-X. (2025) · bioRxiv · doi:10.1101/2025.09.11.675507 · Cited by 5
Li, W., Tang, F., Zhao, M., Omachi, M., & Kato, N. (2025) · IEEE Transactions on Network Science and Engineering · doi:10.1109/tnse.2025.3644352 · Cited by 3
“Inrecentyears,largelanguagemodels(LLMs)havedemon- stratedextraordinarycapabilitiesinnaturallanguageprocess-ing(NLP),includingconversation,reasoning,andtextgener-ation[28],[29],[30].”
Yin, L., Xue, X., Pan, S., Liu, X., Zhou, Y., Nahar, L., Chen, Y., Zhao, J., Zeng, S., & Xu, T. (2025) · Acta Materia Medica · doi:10.15212/amm-2025-0045 · Cited by 6
“These practices establish a robust foundation for applying LLMs in complex, individualized TCM contexts [159].”
Freeman, J., Millikin, R. J., Xu, L., Sharma, I., Moore, B., Lock, C., Shine George, K., Bal, A., Mohanty, C., & Stewart, R. (2025) · BMC Bioinformatics · doi:10.1186/s12859-025-06350-7 · Cited by 4
“General-purpose LLMs [2, 9, 24] achieve state-of-the-art scores on biomedical reasoning and question-answering benchmarks [7, 17, 28].”
SynNER: syntax-infused named entity recognition in the biomedical domain
Imran, M., Zamaraeva, O., & Gómez‐Rodríguez, C. (2025) · JAMIA Open · doi:10.1093/jamiaopen/ooaf149 · Cited by 2
“In this study, we use five biomedical benchmark datasets described in Chen et al. 24 (Table 1).”
Chen, Z., Gao, Y., Gu, S., Yong, Z., Li, L., Wang, R., Lei, Q., & Zeng, S. (2026) · Anesthesiology and Perioperative Science · doi:10.1007/s44254-025-00140-3 · Cited by 4
“However, since its training data spans a wide array of general domains rather than medical-specific datasets, its performance in specialized tasks such as medical reasoning and anesthesia plan generation may encounter limitations [19].”
Assessing Large Language Models for Medical QA: Zero-Shot and LLM-as-a-Judge Evaluation
Adib, S. E. S., Sani, A. A., Esham, E. A., Abrar, A., & Chowdhury, T. M. (2025) · 2025 28th International Conference on Computer and Information Technology (ICCIT) · doi:10.1109/iccit68739.2025.11491589 · Cited by 4
“We employed standardized automatic evaluation metrics commonly used in medical NLP research to assess model performance across multiple dimensions [2], [15]: • BLEU Scores: Measures n-gram overlap between generated and reference answers, providing insights into lexical similarity and content…”
InfluentialHySim-LLM: Embedding-Weighted Fine-Tuning Bounds and Manifold Denoising for Domain-Adapted LLMs
Jaberi-Douraki, M., Sholehrasa, H., Xu, X., & Ramachandran, R. (2025) · arXiv.org · doi:10.48550/arxiv.2510.07796 · Cited by 4
“Recent advances in large language models (LLMs) have revolutionized natural language processing, enabling state-of-the-art performance in text summarization, retrieval, and reasoning [4].”
The application of large language models in qualitative nursing research: A scoping review
Zhou, T., Xing, M., Hu, Y., Liang, J., Ren, Q., Yang, Y., & Ye, L. (2025) · Nursing Outlook · doi:10.1016/j.outlook.2025.102544 · Cited by 6
Self-citationA review on recent advancements of ChatGPT and datafication in healthcare applications
Jagatheesaperumal, S. K., Pandiyarajan, A., Prabadevi, B., Deepa, N., Barreto, A. G., & de Albuquerque, V. H. C. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110885 · Cited by 6
Community-based biomedical context to unlock agentic systems
Kuehl, M., Schaub, D. P., Carli, F., Heumos, L., Fernández-Zapata, C., Kaiser, N., Schaul, J., Panzer, U., Bonn, S., Lobentanzer, S., et al. (2025) · bioRxiv · doi:10.1101/2025.07.21.665729 · Cited by 4
“Despite their potential applications, LLMs have significant limitations in biomedicine as they often generate hallucinations [4], cannot access specialized databases, and lack the necessary domain knowledge and functional capabilities [5], which are crucial for providing reliable scientific outputs.”
An In-Depth Evaluation of Federated Learning on Biomedical Natural Language ProcessingPreprint
Peng, L., Luo, G., Zhou, S.-C., Chen, J., Zhang, R., Xu, Z.-C., & Sun, J. (2023) · medRxiv · doi:10.1101/2023.11.24.23299002 · Cited by 4
“We followed the experimental protocol outlined in a recent study 32 and evaluated all the models on two NER datasets (2018 n2c2 and NCBI-disease) and two RE datasets (2018 n2c2, and GAD).”
MethodSelf-citationBenchmarking zero-shot biomedical relation triplet extraction across language model architectures
Gade, F. S., Lund, O., & Mendoza, M. L. (2025) · Workshop on Biomedical Language Processing (BioNLP) · doi:10.18653/v1/2025.bionlp-1.9
“Multiple papers have benchmarked LLMs for IE tasks on biomedical texts (Dai et al., 2024; Jahan et al., 2024; Chen et al., 2025), and there are multiple established combined benchmark datasets (e.g. BLURB (Gu et al., 2021)) and LLM instruction datasets (e.g. SciRIFF (Wadden et al., 2024)), but two…”
Tutorial: guidance on the use of large language models for medical research
Jin, Q., Wan, N., Leaman, R., Tian, S., Wang, Z., Yang, Y., Wang, Z., Xiong, G., Lai, P.-T., Zhu, Q. L., et al. (2026) · Nature Protocols · doi:10.1038/s41596-026-01408-z · Cited by 15
Self-citationMedMisBench: Measuring Epistemic Resilience of LLMs Under Misleading Medical ContextPreprint
Zhou, H., Zou, X., Wu, J., Wu, S., Yu, J., Segal, B., Niebuhr, T. E., Amro, S., Petrus, M., Momin, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.25.727671 · Cited by 2
Wang, R.-D., Ba, W., Li, Y., Zhou, Y., Liu, B.-W., Wang, B.-Z., Wang, Y.-H., Yang, Z.-D., Zhang, K., Yan, R., et al. (2026) · International Conference on Medical Image Computing and Computer-Assisted Intervention · doi:10.48550/arxiv.2603.01647 · Cited by 3
“Crucially, we introduce a quality control module that utilizes advanced LLMs [6,27,1] to simulate a pathologist’s auditing behavior.”
Fodeh, S., Wang, Y., Ma, L.-H., Talakokkul, S., Alpert, J. M., & Schellhorn, S. (2026) · Artif. Intell. Medicine · doi:10.48550/arxiv.2603.00028 · Cited by 3
“Similarly, BLURB [19] and recent large-scale evaluations [20] target traditional biomedical tasks.”
Zhu, J., Li, J., Zhao, S., Deng, Y., Miao, Y., & Xu, J. (2026) · The Journal of Supercomputing · doi:10.1007/s11227-025-08182-x · Cited by 2
Building Trustworthy AI for Materials Discovery: From Autonomous Laboratories to Z-scores
Amirian, B., Dale, A. S., Kalinin, S. V., & Hattrick-Simpers, J. (2025) · arXiv.org · doi:10.48550/arxiv.2512.01080 · Cited by 3
“Errors should be analyzed to ensure the model meets reliability standards [32].”
Kumari, M., Chauhan, R., Jain, R., & Garg, P. (2025) · Information Fusion · doi:10.1016/j.inffus.2025.103902 · Cited by 2
Chen, D., Wei, Y., He, Z., Kuang, G., Ye, C., An, M., Peng, H. Y., Hu, Y. S., Tao, H., & Cheung, K. M. (2025) · arXiv (Cornell University) · doi:10.48550/arxiv.2511.00588 · Cited by 1
“On the other hand, currently reported evaluation metrics for LLM in health-care were based on question banks to benchmark LLM performance against medical knowledge mastery within specific disease domains or clinical subspecialties[25, 28, 23, 30, 19].”
InfluentialSelf-citation
Metadata
- Authors
- Chen, Q., Hu, Y., Peng, X., Xie, Q., Jin, Q., Gilson, A., Singer, M. B., Ai, X., Lai, P.-T., Wang, Z., Keloth, V. K., Raja, K., Huang, J., He, H., Lin, F., Du, J., Zhang, R., Zheng, W. J., Adelman, R. A., Lu, Z., & Xu, H.
- Affiliations
- National Institutes of Health (US)
- The University of Texas Health Science Center at Houston (US)
- Yale University (US)
- University of Minnesota (US)
- Corresponding author
- Lu, Zhiyong
- Xu, Hua
- ORCID
- Venue
- Nature Communications
- Published
- 2025-04-06
- Volume
- 16
- Issue
- 1
- Pages
- 3280-3280
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11972378
- OpenAlex
- W4409190866
- Cited by
- 219
- References
- 103
- Citations by year
- 2026: 116 · 2025: 76
- FWCI
- 57.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion, cc-by)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- arXiv (Cornell University) (cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (1K99LM01402)
- Topics
- Health Sciences › Medicine › Health Informatics › Biomedical Text Mining and Ontologies
- Physical Sciences › Computer Science › Artificial Intelligence › Topic Modeling
- Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
- Keywords
- large language models, biomedical natural language processing, benchmarking, GPT-4, llamas, fine-tuning, zero-shot learning, few-shot learning, hallucinations, medical question answering, BERT, BART, cost analysis
- MeSH terms
- Large Language Models, Humans, Natural Language Processing, Benchmarking
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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