Automated high-throughput genome editing platform with an AI learning in situ prediction model.
Siwei LiJingjing AnYaqiu LiXiagu ZhuDongdong ZhaoLixian WangYonghui SunYuanzhao YangZaiqiang WuXueli ZhangMeng WangPublished in: Nature communications (2022)
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.
Keyphrases
- crispr cas
- high throughput
- genome editing
- single cell
- high efficiency
- genome wide
- dna damage
- gene expression
- cell therapy
- induced apoptosis
- transcription factor
- artificial intelligence
- machine learning
- deep learning
- stem cells
- small molecule
- cell cycle arrest
- clinical trial
- randomized controlled trial
- electronic health record
- dna methylation
- oxidative stress
- signaling pathway
- mesenchymal stem cells
- study protocol
- pi k akt