Automated high-throughput genome editing platform with an AI learning in situ prediction model
Siwei Li, Jingjing An, Yaqiu Li, Xiagu Zhu, Dongdong Zhao, Lixian Wang, Yonghui Sun, Yuanzhao Yang, Changhao Bi, Xueli Zhang, Meng Wang
Abstract
A great number of cell disease models with pathogenic SNVs are needed for the development of genome editing based therapeutics or broadly basic scientific research. However, the generation of traditional cell disease models is heavily dependent on large-scale manual operations, which is not only time-consuming, but also costly and error-prone. In this study, we devise an automated high-throughput platform, through which thousands of samples are automatically edited within a week, providing edited cells with high efficiency. Based on the large in situ genome editing data obtained by the automatic high-throughput platform, we develop a Chromatin Accessibility Enabled Learning Model (CAELM) to predict the performance of cytosine base editors (CBEs), both chromatin accessibility and the context-sequence are utilized to build the model, which accurately predicts the result of in situ base editing. This work is expected to accelerate the development of BE-based genetic therapies.