Zheng Lujing, Liu Zhenhuan, Yang Yang, Shen Hong-Bin
Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
SJTU Paris Elite Institute of Technology (SPEIT), Shanghai Jiao Tong University, Shanghai 200240, China.
Bioinformatics. 2022 Jan 12;38(3):746-753. doi: 10.1093/bioinformatics/btab718.
Reverse engineering of gene regulatory networks (GRNs) has long been an attractive research topic in system biology. Computational prediction of gene regulatory interactions has remained a challenging problem due to the complexity of gene expression and scarce information resources. The high-throughput spatial gene expression data, like in situ hybridization images that exhibit temporal and spatial expression patterns, has provided abundant and reliable information for the inference of GRNs. However, computational tools for analyzing the spatial gene expression data are highly underdeveloped.
In this study, we develop a new method for identifying gene regulatory interactions from gene expression images, called ConGRI. The method is featured by a contrastive learning scheme and deep Siamese convolutional neural network architecture, which automatically learns high-level feature embeddings for the expression images and then feeds the embeddings to an artificial neural network to determine whether or not the interaction exists. We apply the method to a Drosophila embryogenesis dataset and identify GRNs of eye development and mesoderm development. Experimental results show that ConGRI outperforms previous traditional and deep learning methods by a large margin, which achieves accuracies of 76.7% and 68.7% for the GRNs of early eye development and mesoderm development, respectively. It also reveals some master regulators for Drosophila eye development.
https://github.com/lugimzheng/ConGRI.
Supplementary data are available at Bioinformatics online.
基因调控网络(GRN)的逆向工程长期以来一直是系统生物学中一个引人关注的研究课题。由于基因表达的复杂性和信息资源稀缺,基因调控相互作用的计算预测仍然是一个具有挑战性的问题。高通量空间基因表达数据,如展示时空表达模式的原位杂交图像,为GRN的推断提供了丰富且可靠的信息。然而,用于分析空间基因表达数据的计算工具却极不发达。
在本研究中,我们开发了一种从基因表达图像中识别基因调控相互作用的新方法,称为ConGRI。该方法的特点是采用对比学习方案和深度孪生卷积神经网络架构,它能自动为表达图像学习高级特征嵌入,然后将这些嵌入输入人工神经网络以确定相互作用是否存在。我们将该方法应用于果蝇胚胎发育数据集,并识别出眼睛发育和中胚层发育的GRN。实验结果表明,ConGRI大大优于先前的传统方法和深度学习方法,对于早期眼睛发育和中胚层发育的GRN,其准确率分别达到76.7%和68.7%。它还揭示了果蝇眼睛发育的一些主控调节因子。
https://github.com/lugimzheng/ConGRI。
补充数据可在《生物信息学》在线获取。