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, ther...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54365-0 |
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| _version_ | 1841544486095683584 |
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| author | Wenhui Li Xianyue Jiang Wuke Wang Liya Hou Runze Cai Yongqian Li Qiuxi Gu Qinchang Chen Peixiang Ma Jin Tang Menghao Guo Guohui Chuai Xingxu Huang Jun Zhang Qi Liu |
| author_facet | Wenhui Li Xianyue Jiang Wuke Wang Liya Hou Runze Cai Yongqian Li Qiuxi Gu Qinchang Chen Peixiang Ma Jin Tang Menghao Guo Guohui Chuai Xingxu Huang Jun Zhang Qi Liu |
| author_sort | Wenhui Li |
| collection | DOAJ |
| description | 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, showing promise for CRISPR-based pathogen detection. This study highlights an innovative approach for discovering CRISPR-Cas systems with specific functions, emphasizing their potential in gene editing. |
| format | Article |
| id | doaj-art-06e347abdbb6496da2cdeead59091ae6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-06e347abdbb6496da2cdeead59091ae62025-01-12T12:29:30ZengNature PortfolioNature Communications2041-17232024-11-0115111410.1038/s41467-024-54365-0Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation modelsWenhui Li0Xianyue Jiang1Wuke Wang2Liya Hou3Runze Cai4Yongqian Li5Qiuxi Gu6Qinchang Chen7Peixiang Ma8Jin Tang9Menghao Guo10Guohui Chuai11Xingxu Huang12Jun Zhang13Qi Liu14State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Bioinformatics Department, School of Life Sciences and Technology, Tongji UniversityResearch Center for Life Sciences Computing, Zhejiang LabResearch Center for Life Sciences Computing, Zhejiang LabResearch Center for Life Sciences Computing, Zhejiang LabResearch Center for Life Sciences Computing, Zhejiang LabResearch Center for Life Sciences Computing, Zhejiang LabState Key Laboratory of Reproductive Medicine and Offspring Health, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical UniversityResearch Center for Life Sciences Computing, Zhejiang LabShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineResearch Center for Life Sciences Computing, Zhejiang LabResearch Center for Life Sciences Computing, Zhejiang LabState Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Bioinformatics Department, School of Life Sciences and Technology, Tongji UniversityResearch Center for Life Sciences Computing, Zhejiang LabState Key Laboratory of Reproductive Medicine and Offspring Health, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical UniversityState Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Bioinformatics Department, School of Life Sciences and Technology, Tongji UniversityAbstract 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, showing promise for CRISPR-based pathogen detection. This study highlights an innovative approach for discovering CRISPR-Cas systems with specific functions, emphasizing their potential in gene editing.https://doi.org/10.1038/s41467-024-54365-0 |
| spellingShingle | Wenhui Li Xianyue Jiang Wuke Wang Liya Hou Runze Cai Yongqian Li Qiuxi Gu Qinchang Chen Peixiang Ma Jin Tang Menghao Guo Guohui Chuai Xingxu Huang Jun Zhang Qi Liu Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models Nature Communications |
| title | Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models |
| title_full | Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models |
| title_fullStr | Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models |
| title_full_unstemmed | Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models |
| title_short | Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models |
| title_sort | discovering crispr cas system with self processing pre crrna capability by foundation models |
| url | https://doi.org/10.1038/s41467-024-54365-0 |
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