# AnnoDPO: Protein Functional Annotation Learning with Direct Preference Optimization

arXiv: https://arxiv.org/abs/2506.07035 · HTML: https://mlsanity.com/paper/2506.07035/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Preference optimization for molecular design, one of 10 directions in LLM alignment / RLHF / preference optimisation.
- Builds on 20 of its 45 references that are in the map.
- First posted on arXiv 8 Jun 2025.

## Placed in

- LLM alignment / RLHF / preference optimisation / [Preference optimization for molecular design](https://mlsanity.com/alignment/preference-optimization-for-molecular-design/)

## Builds on (most cited first, 20 of 20)

- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Proximal Policy Optimization Algorithms](https://mlsanity.com/paper/1707.06347/) (2017)
- [Direct Preference Optimization: Your Language Model is Secretly a Reward Model](https://mlsanity.com/paper/2305.18290/) (2023)
- [Deep reinforcement learning from human preferences](https://mlsanity.com/paper/1706.03741/) (2017)
- [Training a Helpful and Harmless Assistant with Reinforcement Learning from Human Feedback](https://mlsanity.com/paper/2204.05862/) (2022)
- [Learning to summarize from human feedback](https://mlsanity.com/paper/2009.01325/) (2020)
- [Fine-Tuning Language Models from Human Preferences](https://mlsanity.com/paper/1909.08593/) (2019)
- [RAFT: Reward rAnked FineTuning for Generative Foundation Model Alignment](https://mlsanity.com/paper/2304.06767/) (2023)
- [Improving alignment of dialogue agents via targeted human judgements](https://mlsanity.com/paper/2209.14375/) (2022)
- [RRHF: Rank Responses to Align Language Models with Human Feedback without tears](https://mlsanity.com/paper/2304.05302/) (2023)
- [Preference Ranking Optimization for Human Alignment](https://mlsanity.com/paper/2306.17492/) (2023)
- [Rewarding Progress: Scaling Automated Process Verifiers for LLM Reasoning](https://mlsanity.com/paper/2410.08146/) (2024)
- [Is DPO Superior to PPO for LLM Alignment? A Comprehensive Study](https://mlsanity.com/paper/2404.10719/) (2024)
- [ProGen: Language Modeling for Protein Generation](https://mlsanity.com/paper/2004.03497/) (2020)
- [GLoRe: When, Where, and How to Improve LLM Reasoning via Global and Local Refinements](https://mlsanity.com/paper/2402.10963/) (2024)
- [ProtST: Multi-Modality Learning of Protein Sequences and Biomedical Texts](https://mlsanity.com/paper/2301.12040/) (2023)
- [OntoProtein: Protein Pretraining With Gene Ontology Embedding](https://mlsanity.com/paper/2201.11147/) (2022)
- [Policy Optimization in RLHF: The Impact of Out-of-preference Data](https://mlsanity.com/paper/2312.10584/) (2023)
- [DeepGO: Predicting protein functions from sequence and interactions using a deep ontology-aware classifier](https://mlsanity.com/paper/1705.05919/) (2017)
- [Controllable Protein Sequence Generation with LLM Preference Optimization](https://mlsanity.com/paper/2501.15007/) (2025)

## Abstract (arXiv)

Deciphering protein function remains a fundamental challenge in protein representation learning. The task presents significant difficulties for protein language models (PLMs) due to the sheer volume of functional annotation categories and the highly imbalanced distribution of annotated instances across biological ontologies. Inspired by the remarkable success of reinforcement learning from human feedback (RLHF) in large language model (LLM) alignment, we propose AnnoDPO, a novel multi-modal framework for protein function prediction that leverages Direct Preference Optimization (DPO) to enhance annotation learning. Our methodology addresses the dual challenges of annotation scarcity and category imbalance through preference-aligned training objectives, establishing a new paradigm for biological knowledge integration in protein representation learning.