An Empirical Analysis of Fine-Tuning Large Language Models on Bioinformatics Literature: PRSGPT and BioStarsGPT

Large language models (LLMs) often lack specialized knowledge for complex bioinformatics applications. We present a reproducible pipeline for fine-tuning LLMs on specialized bioinformatics data, demonstrated through two use cases: PRSGPT, focused on polygenic risk score (PRS) tools, and BioStarsGPT, trained on community forum discussions. The nine-step pipeline integrates diverse data sources, structured preprocessing, prompt-based question-answer (QA) generation (via Google Gemini), natural language inference (NLI) for quality control, semantic deduplication, clustering-based data splitting, and parameter-efficient fine-tuning using LoRA. We fine-tuned three LLMs (LLaMA-3.2-3B, Qwen2.5-7B, Gemma) and benchmarked them on over 14 lexical and semantic metrics. Qwen2.5-7B emerged as the best performer, with BLEU-4 and ROUGE-1 improvements of 82% and 70% for PRSGPT and 6% and 18% for BioStarsGPT, respectively. The open-source datasets produced include over 28,000 QA pairs for PRSGPT and 154,282 for BioStarsGPT. Human evaluation of PRSGPT yielded 61.9% accuracy on the PRS tools comparison task, comparable to Google Gemini (61.4%), but with richer methodological detail and accurate citations. BioStarsGPT demonstrated 59% conceptual accuracy across 142 curated bioinformatics questions. Our pipeline enables scalable, domain-specific fine-tuning of LLMs. It enables privacy-preserving, locally deployable bioinformatics assistants, explores their practical applications, and addresses the challenges, limitations, and mitigation strategies associated with their development and use. Key PointsO_LIWe present a comprehensive 9-step pipeline for fine-tuning large language models on bioinformatics data, demonstrated through PRSGPT (PRS tools) and BioStarsGPT (forum discussions). C_LIO_LIThe pipeline generated over 28,000 QA pairs for PRSGPT from diverse sources (PDFs, GitHub repositories, research articles) and 154,282 QA pairs for BioStarsGPT from community forum discussions. C_LIO_LIQwen2.5-7B emerged as the best-performing model, achieving BLEU-4 improvements of 82% for PRSGPT and 6% for BioStarsGPT, with ROUGE-1 improvements of 70% and 18% respectively. C_LIO_LIThe methodology integrates automated QA generation via Google Gemini, NLI for quality control, semantic deduplication, and parameter-efficient fine-tuning using LoRA, providing a scalable framework for domain-specific LLM adaptation. C_LI