Tree Search-Based Evolutionary Bandits for Protein Sequence Optimization

Jiahao Qiu, Hui Yuan, Jinghong Zhang, Wentao Chen, Huazheng Wang, Mengdi Wang

Research output: Contribution to journalConference articlepeer-review


While modern biotechnologies allow synthesizing new proteins and function measurements at scale, efficiently exploring a protein sequence space and engineering it remains a daunting task due to the vast sequence space of any given protein. Protein engineering is typically conducted through an iterative process of adding mutations to the wild-type or lead sequences, recombination of mutations, and running new rounds of screening. To enhance the efficiency of such a process, we propose a tree search-based bandit learning method, which expands a tree starting from the initial sequence with the guidance of a bandit machine learning model. Under simplified assumptions and a Gaussian Process prior, we provide theoretical analysis and a Bayesian regret bound, demonstrating that the method can efficiently discover a near-optimal design. The full algorithm is compatible with a suite of randomized tree search heuristics, machine learning models, pre-trained embeddings, and bandit techniques. We test various instances of the algorithm across benchmark protein datasets using simulated screens. Experiment results demonstrate that the algorithm is both sample-efficient, diversity-promoting, and able to find top designs using reasonably small mutation counts.

Original languageEnglish (US)
Pages (from-to)14686-14694
Number of pages9
JournalProceedings of the AAAI Conference on Artificial Intelligence
Issue number13
StatePublished - Mar 25 2024
Event38th AAAI Conference on Artificial Intelligence, AAAI 2024 - Vancouver, Canada
Duration: Feb 20 2024Feb 27 2024

All Science Journal Classification (ASJC) codes

  • Artificial Intelligence


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