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Benchmarking large language models for pathogen-disease classification in post-acute infection syndromes.
Syed Mohammed Khalid1, Tom Wölker1, Leidy-Alejandra G Molano1,2
1Clinical Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.
Briefings in Bioinformatics
|March 6, 2026
Summary
Large language models (LLMs) can identify pathogen-disease links in Post-Acute Infection Syndromes (PAIS) literature. Zero-shot prompting with models like Mistral-Small-Instruct-2409 proved most effective for this complex task.
Area of Science:
- Computational biology and bioinformatics
- Natural language processing in medicine
- Infectious disease research
Background:
- Post-Acute Infection Syndromes (PAIS) are persistent conditions following infections like SARS-CoV-2.
- Extracting pathogen-disease associations from vast biomedical literature is challenging due to data heterogeneity.
- Limited research specifically addresses PAIS within the broader scientific corpus.
Purpose of the Study:
- To evaluate the efficacy of large language models (LLMs) in extracting pathogen-disease associations for PAIS.
- To benchmark various open-source LLMs and prompting strategies for this classification task.
- To identify optimal LLM architectures and methods for PAIS literature analysis.
Main Methods:
- A binary classification task was performed on 1000 manually labeled PubMed abstracts.
- A diverse set of open-source LLMs (4B-70B parameters) were evaluated, including generalist, reasoning, and biomedical models.
- Prompting strategies including zero-shot, few-shot, and Chain of Thought (CoT) were tested.
Main Results:
- LLM performance varied significantly based on model size, architecture, and prompting technique.
- Zero-shot prompting yielded the best results, with Mistral-Small-Instruct-2409 and Llama-3.1-Nemotron-70B-Instruct achieving high balanced accuracy and macro-F1 scores.
- Reasoning models showed improved performance with few-shot and CoT prompting, unlike generalist models.
Conclusions:
- LLMs, particularly with zero-shot prompting, are effective tools for identifying pathogen-disease associations in PAIS literature.
- Model selection and prompting strategy are critical for optimizing performance in biomedical text mining.
- This approach can aid researchers in navigating complex biomedical data for PAIS research.