Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System
Abstract The CRISPR‐Cas12a system has gained significant attention as a rapid nucleic acid diagnostic tool due to its crRNA‐guided trans‐cleavage activity. Accurately predicting the activity of different targets is significant to facilitate the crRNA availability but remains challenging. In this stu...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202501269 |
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| author | Zhihao Yao Wanglu Li Kaiyu He Hongmei Wang Yan Xu Qun Wu Liu Wang Yao Nie |
| author_facet | Zhihao Yao Wanglu Li Kaiyu He Hongmei Wang Yan Xu Qun Wu Liu Wang Yao Nie |
| author_sort | Zhihao Yao |
| collection | DOAJ |
| description | Abstract The CRISPR‐Cas12a system has gained significant attention as a rapid nucleic acid diagnostic tool due to its crRNA‐guided trans‐cleavage activity. Accurately predicting the activity of different targets is significant to facilitate the crRNA availability but remains challenging. In this study, a novel approach is presented that combines molecular dynamics simulations and neural network modeling to predict the trans‐cleavage activity. Unlike conventional tools that rely solely on the base sequences, our method integrated sequence features and molecular interaction features of DNA in the CRISPR‐Cas12a system, significantly improving prediction accuracy. Through feature importance analysis, key sequence features that influence Cas12a trans‐cleavage activity are identified. Additionally, a crRNA‐DNA library with over 23 456 feature sequences from representative viruses and bacteria is established, and validated the high predictive accuracy of the model (Pearson's r = 0.9328) by screening crRNAs from reference targets. This study offers new insights into the molecular interactions of Cas12a/crRNA‐DNA and provides a reliable framework for optimizing crRNA design, facilitating the application of the CRISPR‐Cas12a in rapid nucleic acid diagnostics. |
| format | Article |
| id | doaj-art-6b7a53c4e398438eaa948fee55284442 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-6b7a53c4e398438eaa948fee552844422025-08-20T03:28:58ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202501269Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a SystemZhihao Yao0Wanglu Li1Kaiyu He2Hongmei Wang3Yan Xu4Qun Wu5Liu Wang6Yao Nie7The Key Laboratory of Industrial Biotechnology Ministry of Education State Key Laboratory of Food Science and Resources School of Biotechnology Jiangnan University Wuxi Jiangsu 214122 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐products Institute of Agro‐product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐products Institute of Agro‐product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐products Institute of Agro‐product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaThe Key Laboratory of Industrial Biotechnology Ministry of Education State Key Laboratory of Food Science and Resources School of Biotechnology Jiangnan University Wuxi Jiangsu 214122 ChinaThe Key Laboratory of Industrial Biotechnology Ministry of Education State Key Laboratory of Food Science and Resources School of Biotechnology Jiangnan University Wuxi Jiangsu 214122 ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐products Institute of Agro‐product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou 310021 ChinaThe Key Laboratory of Industrial Biotechnology Ministry of Education State Key Laboratory of Food Science and Resources School of Biotechnology Jiangnan University Wuxi Jiangsu 214122 ChinaAbstract The CRISPR‐Cas12a system has gained significant attention as a rapid nucleic acid diagnostic tool due to its crRNA‐guided trans‐cleavage activity. Accurately predicting the activity of different targets is significant to facilitate the crRNA availability but remains challenging. In this study, a novel approach is presented that combines molecular dynamics simulations and neural network modeling to predict the trans‐cleavage activity. Unlike conventional tools that rely solely on the base sequences, our method integrated sequence features and molecular interaction features of DNA in the CRISPR‐Cas12a system, significantly improving prediction accuracy. Through feature importance analysis, key sequence features that influence Cas12a trans‐cleavage activity are identified. Additionally, a crRNA‐DNA library with over 23 456 feature sequences from representative viruses and bacteria is established, and validated the high predictive accuracy of the model (Pearson's r = 0.9328) by screening crRNAs from reference targets. This study offers new insights into the molecular interactions of Cas12a/crRNA‐DNA and provides a reliable framework for optimizing crRNA design, facilitating the application of the CRISPR‐Cas12a in rapid nucleic acid diagnostics.https://doi.org/10.1002/advs.202501269activity predictionCRISPR‐Cas12adeep learningmolecular dynamics simulationtrans‐cleavage |
| spellingShingle | Zhihao Yao Wanglu Li Kaiyu He Hongmei Wang Yan Xu Qun Wu Liu Wang Yao Nie Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System Advanced Science activity prediction CRISPR‐Cas12a deep learning molecular dynamics simulation trans‐cleavage |
| title | Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System |
| title_full | Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System |
| title_fullStr | Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System |
| title_full_unstemmed | Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System |
| title_short | Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR‐Cas12a System |
| title_sort | facilitating crrna design by integrating dna interaction features of crispr cas12a system |
| topic | activity prediction CRISPR‐Cas12a deep learning molecular dynamics simulation trans‐cleavage |
| url | https://doi.org/10.1002/advs.202501269 |
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