# Meta-Learning for Cross-Task Generalization in Protein Mutation Property Prediction

arXiv: https://arxiv.org/abs/2510.20943 · HTML: https://mlsanity.com/paper/2510.20943/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 48 references that are in the map.
- First posted on arXiv 23 Oct 2025.

## Builds on (most cited first, 12 of 12)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Model-Agnostic Meta-Learning for Fast Adaptation of Deep Networks](https://mlsanity.com/paper/1703.03400/) (2017)
- [Overcoming catastrophic forgetting in neural networks](https://mlsanity.com/paper/1612.00796/) (2016)
- [PeptideBERT: A Language Model based on Transformers for Peptide Property Prediction](https://mlsanity.com/paper/2309.03099/) (2023)
- [Multimodal Language and Graph Learning of Adsorption Configuration in Catalysis](https://mlsanity.com/paper/2401.07408/) (2024)
- [Large Language Model Agent for Modular Task Execution in Drug Discovery](https://mlsanity.com/paper/2507.02925/) (2025)
- [LLM-guided Chemical Process Optimization with a Multi-Agent Approach](https://mlsanity.com/paper/2506.20921/) (2025)
- [Automating MD simulations for Proteins using Large language Models: NAMD-Agent](https://mlsanity.com/paper/2507.07887/) (2025)
- [MOFGPT: Generative Design of Metal-Organic Frameworks using Language Models](https://mlsanity.com/paper/2506.00198/) (2025)
- [Multi-Peptide: Multimodality Leveraged Language-Graph Learning of Peptide Properties](https://mlsanity.com/paper/2407.03380/) (2024)

## Abstract (arXiv)

Protein mutations can have profound effects on biological function, making accurate prediction of property changes critical for drug discovery, protein engineering, and precision medicine. Current approaches rely on fine-tuning protein-specific transformers for individual datasets, but struggle with cross-dataset generalization due to heterogeneous experimental conditions and limited target domain data. We introduce two key innovations: (1) the first application of Model-Agnostic Meta-Learning (MAML) to protein mutation property prediction, and (2) a novel mutation encoding strategy using separator tokens to directly incorporate mutations into sequence context. We build upon transformer architectures integrating them with MAML to enable rapid adaptation to new tasks through minimal gradient steps rather than learning dataset-specific patterns. Our mutation encoding addresses the critical limitation where standard transformers treat mutation positions as unknown tokens, significantly degrading performance. Evaluation across three diverse protein mutation datasets (functional fitness, thermal stability, and solubility) demonstrates significant advantages over traditional fine-tuning. In cross-task evaluation, our meta-learning approach achieves 29% better accuracy for functional fitness with 65% less training time, and 94% better accuracy for solubility with 55% faster training. The framework maintains consistent training efficiency regardless of dataset size, making it particularly valuable for industrial applications and early-stage protein design where experimental data is limited. This work establishes a systematic application of meta-learning to protein mutation analysis and introduces an effective mutation encoding strategy, offering transformative methodology for cross-domain generalization in protein engineering.