Key Laboratory of Intelligent Computing & Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, 111 Jiulong Road, Hefei, 230601, Anhui, China.
Key Laboratory of Intelligent Computing & Signal Processing of Ministry of Education, School of Computer Science and Technology, Anhui University, 111 Jiulong Road, Hefei, 230601, Anhui, China.
Comput Biol Med. 2024 Sep;179:108835. doi: 10.1016/j.compbiomed.2024.108835. Epub 2024 Jul 11.
Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships.
基因调控网络(GRNs)对于理解生物分子机制和过程至关重要。通过鲤鱼疱疹病毒(SVCV)感染构建鲤鱼上皮瘤细胞(EPC)中的 GRN,有助于理解增强鲤鱼生存能力的免疫调节机制。尽管已经使用了许多计算方法来推断 GRN,但缺乏专门用于预测 SVCV 感染后 EPC 细胞 GRN 的方法。此外,大多数现有方法主要侧重于基因表达特征,而忽略了已知 GRN 中宝贵的网络结构信息。在这项研究中,我们提出了一种新的有监督深度神经网络,称为 MEFFGRN(基于矩阵增强和特征融合的基因调控网络推断方法),用于准确预测 SVCV 感染后 EPC 细胞的 GRN。MEFFGRN 同时考虑了基因表达数据和已知 GRN 的网络结构信息,并引入了矩阵增强方法来解决已知 GRN 的稀疏性问题,提取更丰富的网络结构信息。为了优化卷积神经网络(CNN)在图像处理中的优势,基因表达和增强的 GRN 数据分别转换为每个基因对的直方图图像。随后,分别将这些直方图输入 CNN 进行训练,以获得相应的基因表达和网络结构特征。此外,引入了特征融合机制,以全面整合基因表达和网络结构特征。这种集成考虑了每个特征的特异性及其交互信息,从而在融合过程中产生更全面和精确的特征表示。来自真实世界和基准数据集的实验结果表明,MEFFGRN 与最先进的计算方法相比具有竞争力的性能。此外,来自 SVCV 感染的 EPC 细胞的研究结果表明,MEFFGRN 可以预测新的基因调控关系。