IEEE/ACM Trans Comput Biol Bioinform. 2024 May-Jun;21(3):480-491. doi: 10.1109/TCBB.2024.3374430. Epub 2024 Jun 5.
Transcription factors (TFs) regulation is required for the vast majority of biological processes in living organisms. Some diseases may be caused by improper transcriptional regulation. Identifying the target genes of TFs is thus critical for understanding cellular processes and analyzing disease molecular mechanisms. Computational approaches can be challenging to employ when attempting to predict potential interactions between TFs and target genes. In this paper, we present a novel graph model (PPRTGI) for detecting TF-target gene interactions using DNA sequence features. Feature representations of TFs and target genes are extracted from sequence embeddings and biological associations. Then, by combining the aggregated node feature with graph structure, PPRTGI uses a graph neural network with personalized PageRank to learn interaction patterns. Finally, a bilinear decoder is applied to predict interaction scores between TF and target gene nodes. We designed experiments on six datasets from different species. The experimental results show that PPRTGI is effective in regulatory interaction inference, with our proposed model achieving an area under receiver operating characteristic score of 93.87% and an area under precision-recall curves score of 88.79% on the human dataset. This paper proposes a new method for predicting TF-target gene interactions, which provides new insights into modeling molecular networks and can thus be used to gain a better understanding of complex biological systems.
转录因子(TFs)的调控对于生物体的绝大多数生物过程都是必需的。一些疾病可能是由于转录调控不当引起的。因此,鉴定 TF 的靶基因对于理解细胞过程和分析疾病分子机制至关重要。当试图预测 TF 和靶基因之间的潜在相互作用时,计算方法可能具有挑战性。在本文中,我们提出了一种新的图模型(PPRTGI),用于使用 DNA 序列特征检测 TF-靶基因相互作用。TF 和靶基因的特征表示从序列嵌入和生物学关联中提取。然后,PPRTGI 通过结合聚合节点特征和图结构,使用具有个性化 PageRank 的图神经网络来学习相互作用模式。最后,应用双线性解码器预测 TF 和靶基因节点之间的相互作用得分。我们在来自不同物种的六个数据集上设计了实验。实验结果表明,PPRTGI 在调控相互作用推断中是有效的,我们提出的模型在人类数据集上的接收器操作特性曲线下面积得分为 93.87%,精度-召回曲线下面积得分为 88.79%。本文提出了一种新的预测 TF-靶基因相互作用的方法,为建模分子网络提供了新的思路,从而可以更好地理解复杂的生物系统。