GraphTGI: an attention-based graph embedding model for predicting TF-target gene interactions.

MOTIVATION: Interaction between transcription factor (TF) and its target genes establishes the knowledge foundation for biological researches in transcriptional regulation, the number of which is, however, still limited by biological techniques. Existing computational methods relevant to the prediction of TF-target interactions are mostly proposed for predicting binding sites, rather than directly predicting the interactions. To this end, we propose here a graph attention-based autoencoder model to predict TF-target gene interactions using the information of the known TF-target gene interaction network combined with two sequential and chemical gene characters, considering that the unobserved interactions between transcription factors and target genes can be predicted by learning the pattern of the known ones. To the best of our knowledge, the proposed model is the first attempt to solve this problem by learning patterns from the known TF-target gene interaction network. RESULTS: In this paper, we formulate the prediction task of TF-target gene interactions as a link prediction problem on a complex knowledge graph and propose a deep learning model called GraphTGI, which is composed of a graph attention-based encoder and a bilinear decoder. We evaluated the prediction performance of the proposed method on a real dataset, and the experimental results show that the proposed model yields outstanding performance with an average AUC value of 0.8864 +/- 0.0057 in the 5-fold cross-validation. It is anticipated that the GraphTGI model can effectively and efficiently predict TF-target gene interactions on a large scale. AVAILABILITY: Python code and the datasets used in our studies are made available at https://github.com/YanghanWu/GraphTGI.

Heterogeneous graph embedding model for predicting interactions between TF and target gene.

MOTIVATION: Identifying the target genes of transcription factors (TFs) is of great significance for biomedical researches. However, using biological experiments to identify TF-target gene interactions is still time consuming, expensive and limited to small scale. Existing computational methods for predicting underlying genes for TF to target is mainly proposed for their binding sites rather than the direct interaction. To bridge this gap, we in this work proposed a deep learning prediction model, named HGETGI, to identify the new TF-target gene interaction. Specifically, the proposed HGETGI model learns the patterns of the known interaction between TF and target gene complemented with their involvement in different human disease mechanisms. It performs prediction based on random walk for meta-path sampling and node embedding in a skip-gram manner. RESULTS: We evaluated the prediction performance of the proposed method on a real dataset and the experimental results show that it can achieve the average area under the curve of 0.8519 ± 0.0731 in fivefold cross validation. Besides, we conducted case studies on the prediction of two important kinds of TF, NFKB1 and TP53. As a result, 33 and 32 in the top-40 ranking lists of NFKB1 and TP53 were successfully confirmed by looking up another public database (hTftarget). It is envisioned that the proposed HGETGI method is feasible and effective for predicting TF-target gene interactions on a large scale. AVAILABILITY AND IMPLEMENTATION: The source code and dataset are available at https://github.com/PGTSING/HGETGI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.