# Aligning LLMs with Biomedical Knowledge using Balanced Fine-Tuning

arXiv: https://arxiv.org/abs/2511.21075 · HTML: https://mlsanity.com/paper/2511.21075/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 33 of its 80 references that are in the map.
- First posted on arXiv 26 Nov 2025.

## Builds on (most cited first, 30 of 33)

- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [Measuring Massive Multitask Language Understanding](https://mlsanity.com/paper/2009.03300/) (2020)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Measuring Mathematical Problem Solving With the MATH Dataset](https://mlsanity.com/paper/2103.03874/) (2021)
- [Deep reinforcement learning from human preferences](https://mlsanity.com/paper/1706.03741/) (2017)
- [Qwen2 Technical Report](https://mlsanity.com/paper/2407.10671/) (2024)
- [HybridFlow: A Flexible and Efficient RLHF Framework](https://mlsanity.com/paper/2409.19256/) (2024)
- [BioBERT: a pre-trained biomedical language representation model for biomedical text mining](https://mlsanity.com/paper/1901.08746/) (2019)
- [LlamaFactory: Unified Efficient Fine-Tuning of 100+ Language Models](https://mlsanity.com/paper/2403.13372/) (2024)
- [Solving Quantitative Reasoning Problems with Language Models](https://mlsanity.com/paper/2206.14858/) (2022)
- [gpt-oss-120b & gpt-oss-20b Model Card](https://mlsanity.com/paper/2508.10925/) (2025)
- [PubMedQA: A Dataset for Biomedical Research Question Answering](https://mlsanity.com/paper/1909.06146/) (2019)
- [OlympiadBench: A Challenging Benchmark for Promoting AGI with Olympiad-Level Bilingual Multimodal Scientific Problems](https://mlsanity.com/paper/2402.14008/) (2024)
- [Enhancing Chat Language Models by Scaling High-quality Instructional Conversations](https://mlsanity.com/paper/2305.14233/) (2023)
- [RAFT: Reward rAnked FineTuning for Generative Foundation Model Alignment](https://mlsanity.com/paper/2304.06767/) (2023)
- [CMMLU: Measuring massive multitask language understanding in Chinese](https://mlsanity.com/paper/2306.09212/) (2023)
- [HealthBench: Evaluating Large Language Models Towards Improved Human Health](https://mlsanity.com/paper/2505.08775/) (2025)
- [Text and Code Embeddings by Contrastive Pre-Training](https://mlsanity.com/paper/2201.10005/) (2022)
- [ScispaCy: Fast and Robust Models for Biomedical Natural Language Processing](https://mlsanity.com/paper/1902.07669/) (2019)
- [Deep Think with Confidence](https://mlsanity.com/paper/2508.15260/) (2025)
- [A Survey of Reinforcement Learning for Large Reasoning Models](https://mlsanity.com/paper/2509.08827/) (2025)
- [On the Generalization of SFT: A Reinforcement Learning Perspective with Reward Rectification](https://mlsanity.com/paper/2508.05629/) (2025)
- [All Roads Lead to Likelihood: The Value of Reinforcement Learning in Fine-Tuning](https://mlsanity.com/paper/2503.01067/) (2025)
- [UFT: Unifying Supervised and Reinforcement Fine-Tuning](https://mlsanity.com/paper/2505.16984/) (2025)
- [CRISPR-GPT for Agentic Automation of Gene-editing Experiments](https://mlsanity.com/paper/2404.18021/) (2024)
- [How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities](https://mlsanity.com/paper/2409.11654/) (2024)
- [Learning from models beyond fine-tuning](https://mlsanity.com/paper/2310.08184/) (2023)
- [Supervised Fine Tuning on Curated Data is Reinforcement Learning (and can be improved)](https://mlsanity.com/paper/2507.12856/) (2025)
- [Reinforcement Learning Meets Large Language Models: A Survey of Advancements and Applications Across the LLM Lifecycle](https://mlsanity.com/paper/2509.16679/) (2025)
- [Large Language Models as Biomedical Hypothesis Generators: A Comprehensive Evaluation](https://mlsanity.com/paper/2407.08940/) (2024)

## Built on by (most cited first, 3 of 3)

- [From Tokens to Regions: CUDA-Sensitive Instruction Tuning for GPU Kernel Generation](https://mlsanity.com/paper/2606.16231/) (2026)
- [PertMind: Eliciting Emergent Biological Reasoning in LLM via Reinforcement Learning on Cellular Perturbation Data](https://mlsanity.com/paper/2608.16419/) (2026)
- [Conditional Rank Allocation for Taxonomy-Aware Medical Language Model Adaptation](https://mlsanity.com/paper/2610.06765/) (2026)

## Abstract (arXiv)

Engineering LLMs to accelerate life sciences research requires a robust alignment with biomedical knowledge. We observe that biomedical text exhibits a fundamentally different uncertainty structure from general text: dense low-confidence runs encode epistemic knowledge gaps (dense causal chains, rare entities) rather than the sparse aleatoric stylistic variation typical of general text. Based on this discovery, we propose Balanced Fine-Tuning (BFT), a dual-scale post-training method that combines group-normalized token reweighting with sequence-level reallocation toward knowledge-dense samples exhibiting dense epistemic uncertainty. Across medical evaluation, biological reasoning, sparse-reward RL, and biological representation tasks, BFT provides more consistent gains than SFT and DFT under a shared training setup. When replacing the default closed-source backbones in GeneAgent (GPT-4o) and VCWorld (Gemini-2.5-Flash), the BFT-aligned 70B model delivers stronger performance across biological process reasoning and chemical perturbation prediction. Critically, all BFT variants further improve after subsequent GRPO with sparse rewards, while SFT and DFT degrade, suggesting that epistemic-aware post-training provides a more robust policy initialization. Beyond text generation, BFT-aligned LLMs produce more accurate and professional biomedical profile texts; after encoding these profiles with a text embedding model, the resulting representations support gene-level, cell-level, and perturbation-response tasks, suggesting that BFT-enhanced generation can facilitate biological representation and, in turn, broader biomedical downstream tasks.