Predicting CRISPR Cas9 Off-Target Activities With a Two-Stage Deep Learning Framework

The CRISPR-Cas9 system, found across bacteria and archaea, enables efficient genome engineering in eukaryotic cells. There is a challenge that Cas9 guide RNA may cause off-target activities. Although numbers of methods have been proposed to predict off-target activities in guide RNA designing, this procedure involves numerous potential off-target sites, which causes label imbalance problem. To address this problem, we developed a deep learning framework, named CAF-Net (Cas9 Augmentation and Finetune Network), for predicting off-target activities of CRISPR-Cas9. First, we pretrain an embedding model to extract features from target and guide sequence pairs. Subsequently, data augmentation is applied to these features. And finally, the model is finetuned with synthetic samples. Evaluation results demonstrate its performance on published datasets.