Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models.

ABSTRACT: The discovery of CRISPR-Cas systems has paved the way for advanced gene editing tools. However, traditional Cas discovery methods relying on sequence similarity may miss distant homologs and aren't suitable for functional recognition. With protein large language models (LLMs) evolving, there is potential for Cas system modeling without extensive training data. Here, we introduce CHOOSER (Cas HOmlog Observing and SElf-processing scReening), an AI framework for alignment-free discovery of CRISPR-Cas systems with self-processing pre-crRNA capability using protein foundation models. By using CHOOSER, we identify 11 Casλ homologs, nearly doubling the known catalog. Notably, one homolog, EphcCasλ, is experimentally validated for self-processing pre-crRNA, DNA cleavage, and trans-cleavage, showin

SUBMITTER: Li W 

PROVIDER: S-EPMC11576732 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature