MATL: A deep neural network using multi-scale convolutions and transformer for transcription factor binding site prediction

Transcription factors bind to specific sequences of DNA known as transcription factor binding sites (TFBSs) in order to regulate gene expression. Identifying TFBSs is crucial for deciphering gene expression mechanisms, understanding in vitro life characteristics, and drug design. In recent years, many deep learning methods that utilize only the sequence features or a combination of sequence and shape features have been developed to predict TFBSs. However, these methods have not fully considered the characteristics of TFBSs, and their encoding strategies are relatively simplistic, thereby failing to capture the complex dependencies hidden within TFBSs. To address these issues, we propose a novel deep neural network model called MATL, which integrates sequence and shape features for TFBSs prediction. The model employs techniques such as multi-scale convolution and Transformer, and combines different modules for feature extraction based on the distribution patterns of different feature matrices. Additionally, we introduce transfer learning to address the issue of unsatisfactory prediction results due to insufficient training data in some datasets. As the results indicate, MATL exhibits excellent predictive performance on 165 validated ChIP-seq datasets, surpassing state-of-the-art methods. We also conducted ablation experiments on sequence encoding, feature extraction, and shape modules used in this study, and demonstrated that these modules play a positive role in predicting TFBSs. Moreover, the results also indicated that transfer learning can improve prediction accuracy for some TFBSs datasets with small amounts of data. The source code of MATL is available at https://github.com/LittleWhiteKing/MATL.