deepTAD: an approach for identifying topologically associated domains based on convolutional neural network and transformer model.

Motivation: Topologically associated domains (TADs) play a key role in the 3D organization and function of genomes, and accurate detection of TADs is essential for revealing the relationship between genomic structure and function. Most current methods are developed to extract features in Hi-C interaction matrix to identify TADs. However, due to complexities in Hi-C contact matrices, it is difficult to directly extract features associated with TADs, which prevents current methods from identifying accurate TADs.

Results: In this paper, a novel method is proposed, deepTAD, which is developed based on a convolutional neural network (CNN) and transformer model. First, based on Hi-C contact matrix, deepTAD utilizes CNN to directly extract features associated with TAD boundaries. Next, deepTAD takes advantage of the transformer model to analyze the variation features around TAD boundaries and determines the TAD boundaries. Second, deepTAD uses the Wilcoxon rank-sum test to further identify false-positive boundaries. Finally, deepTAD computes cosine similarity among identified TAD boundaries and assembles TAD boundaries to obtain hierarchical TADs. The experimental results show that TAD boundaries identified by deepTAD have a significant enrichment of biological features, including structural proteins, histone modifications, and transcription start site loci. Additionally, when evaluating the completeness and accuracy of identified TADs, deepTAD has a good performance compared with other methods. The source code of deepTAD is available at https://github.com/xiaoyan-wang99/deepTAD.