CRISPR/Cas9 is a powerful genome-editing tool in biology, but its wide applications are challenged by a lack of knowledge governing single-guide RNA (sgRNA) activity. Several deep-learning-based methods have been developed for the prediction of on-target activity. However, there is still room for improvement. Here, we proposed a hybrid neural network named CrnnCrispr, which integrates a convolutional neural network and a recurrent neural network for on-target activity prediction. We performed unbiased experiments with four mainstream methods on nine public datasets with varying sample sizes. Additionally, we incorporated a transfer learning strategy to boost the prediction power on small-scale datasets. Our results showed that CrnnCrispr outperformed existing methods in terms of accuracy and generalizability. Finally, we applied a visualization approach to investigate the generalizable nucleotide-position-dependent patterns of sgRNAs for on-target activity, which shows potential in terms of model interpretability and further helps in understanding the principles of sgRNA design.
Keywords: CRISPR/Cas9; DeepSHAP; deep learning; on-target; sgRNA.