# TCR-GPT: Integrating Autoregressive Model and Reinforcement Learning for T-Cell Receptor Repertoires Generation

arXiv: https://arxiv.org/abs/2408.01156 · HTML: https://mlsanity.com/paper/2408.01156/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 10 of its 27 references that are in the map.
- First posted on arXiv 2 Aug 2024.

## Builds on (most cited first, 10 of 10)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [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)
- [Empirical Evaluation of Gated Recurrent Neural Networks on Sequence Modeling](https://mlsanity.com/paper/1412.3555/) (2014)
- [An Introduction to Convolutional Neural Networks](https://mlsanity.com/paper/1511.08458/) (2015)
- [MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Design](https://mlsanity.com/paper/2203.14500/) (2022)
- [Toward Diverse Text Generation with Inverse Reinforcement Learning](https://mlsanity.com/paper/1804.11258/) (2018)
- [Computer-Aided Multi-Objective Optimization in Small Molecule Discovery](https://mlsanity.com/paper/2210.07209/) (2022)
- [Offline Reinforcement Learning from Human Feedback in Real-World Sequence-to-Sequence Tasks](https://mlsanity.com/paper/2011.02511/) (2020)
- [Preference-based Interactive Multi-Document Summarisation](https://mlsanity.com/paper/1906.02923/) (2019)

## Abstract (arXiv)

T-cell receptors (TCRs) play a crucial role in the immune system by recognizing and binding to specific antigens presented by infected or cancerous cells. Understanding the sequence patterns of TCRs is essential for developing targeted immune therapies and designing effective vaccines. Language models, such as auto-regressive transformers, offer a powerful solution to this problem by learning the probability distributions of TCR repertoires, enabling the generation of new TCR sequences that inherit the underlying patterns of the repertoire. We introduce TCR-GPT, a probabilistic model built on a decoder-only transformer architecture, designed to uncover and replicate sequence patterns in TCR repertoires. TCR-GPT demonstrates an accuracy of 0.953 in inferring sequence probability distributions measured by Pearson correlation coefficient. Furthermore, by leveraging Reinforcement Learning(RL), we adapted the distribution of TCR sequences to generate TCRs capable of recognizing specific peptides, offering significant potential for advancing targeted immune therapies and vaccine development. With the efficacy of RL, fine-tuned pretrained TCR-GPT models demonstrated the ability to produce TCR repertoires likely to bind specific peptides, illustrating RL's efficiency in enhancing the model's adaptability to the probability distributions of biologically relevant TCR sequences.