Interpretable single-cell transcription factor prediction based on deep learning with attention mechanism

Abstract

Predicting the transcription factor binding site (TFBS) in the whole genome range is essential in exploring the rule of gene transcription control. Although many deep learning methods to predict TFBS have been proposed, predicting TFBS using single-cell ATAC-seq data and embedding attention mechanisms needs to be improved. To this end, we present IscPAM, an interpretable method based on deep learning with an attention mechanism to predict single-cell transcription factors. Our model adopts the convolution neural network to extract the data feature and optimize the pre-trained model. In particular, the model obtains faster training and prediction due to the embedded attention mechanism. For datasets, we take ATAC-seq, ChIP-seq, and DNA sequences data for the pre-trained model, and single-cell ATAC-seq data is used to predict the TF binding graph in the given cell. We verify the interpretability of the model through ablation experiments and sensitivity analysis. IscPAM can efficiently predict the combination of whole genome transcription factors in single cells and study cellular heterogeneity through chromatin accessibility of related diseases.

Keywords: Attention mechanism; Interpretable model; Single-cell; Transcription factor prediction.