Title
High-resolution transcription factor binding sites prediction improved performance and interpretability by deep learning method
Abstract
Transcription factors (TFs) are essential proteins in regulating the spatiotemporal expression of genes. It is crucial to infer the potential transcription factor binding sites (TFBSs) with high resolution to promote biology and realize precision medicine. Recently, deep learning-based models have shown exemplary performance in the prediction of TFBSs at the base-pair level. However, the previous models fail to integrate nucleotide position information and semantic information without noisy responses. Thus, there is still room for improvement. Moreover, both the inner mechanism and prediction results of these models are challenging to interpret. To this end, the Deep Attentive Encoder-Decoder Neural Network (D-AEDNet) is developed to identify the location of TFs-DNA binding sites in DNA sequences. In particular, our model adopts Skip Architecture to leverage the nucleotide position information in the encoder and removes noisy responses in the information fusion process by Attention Gate. Simultaneously, the Transcription Factor Motif Discovery based on Sliding Window (TF-MoDSW), an approach to discover TFs-DNA binding motifs by utilizing the output of neural networks, is proposed to understand the biological meaning of the predicted result. On ChIP-exo datasets, experimental results show that D-AEDNet has better performance than competing methods. Besides, we authenticate that Attention Gate can improve the interpretability of our model by ways of visualization analysis. Furthermore, we confirm that ability of D-AEDNet to learn TFs-DNA binding motifs outperform the state-of-the-art methods and availability of TF-MoDSW to discover biological sequence motifs in TFs-DNA interaction by conducting experiment on ChIP-seq datasets.
Year
DOI
Venue
2021
10.1093/bib/bbab273
BRIEFINGS IN BIOINFORMATICS
Keywords
DocType
Volume
transcription factor binding sites, Attention Gate, interpretability, motif discovery
Journal
22
Issue
ISSN
Citations 
6
1467-5463
0
PageRank 
References 
Authors
0.34
0
5
Name
Order
Citations
PageRank
Yongqing Zhang143.79
Zixuan Wang2912.65
Yuanqi Zeng300.34
Jiliu Zhou445058.21
quan zou555867.61