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CVGAE: A Self-Supervised Generative Method for Gene Regulatory Network Inference Using Single-Cell RNA Sequencing Data

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Abstract

Gene regulatory network (GRN) inference based on single-cell RNA sequencing data (scRNAseq) plays a crucial role in understanding the regulatory mechanisms between genes. Various computational methods have been employed for GRN inference, but their performance in terms of network accuracy and model generalization is not satisfactory, and their poor performance is caused by high-dimensional data and network sparsity. In this paper, we propose a self-supervised method for gene regulatory network inference using single-cell RNA sequencing data (CVGAE). CVGAE uses graph neural network for inductive representation learning, which merges gene expression data and observed topology into a low-dimensional vector space. The well-trained vectors will be used to calculate mathematical distance of each gene, and further predict interactions between genes. In overall framework, FastICA is implemented to relief computational complexity caused by high dimensional data, and CVGAE adopts multi-stacked GraphSAGE layers as an encoder and an improved decoder to overcome network sparsity. CVGAE is evaluated on several single cell datasets containing four related ground-truth networks, and the result shows that CVGAE achieve better performance than comparative methods. To validate learning and generalization capabilities, CVGAE is applied in few-shot environment by change the ratio of train set and test set. In condition of few-shot, CVGAE obtains comparable or superior performance.

Graphical Abstract

CVGAE utilizes a beta variational autoencoder framework in conjunction with graph neural networks to characterize the underlying gene regulatory networks in single-cell gene expression data. The model employs multiple stacked SAGE layers to produce embedding representations of domain nodes, ensuring that the vector representation adheres to a multivariate Gaussian distribution. CVGAE leverages further convolutional computation and multi-layer perceptrons to determine the strength of interactions between nodes.

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Funding

The Scientific Research Fund of Hunan Provincial Education Department, 22A0101, Wei Liu

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Authors and Affiliations

  1. School of Computer Science, Xiangtan University, Xiangtan, 411105, China

    Wei Liu & Zhijie Teng

  2. School of Computer Science and Engineering, Hunan Institute of Technology, Hengyang, 412002, China

    Zejun Li

  3. School of Electronic and Information Engineering, Suzhou University of Science and Technology, Suzhou, 215009, China

    Jing Chen

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  1. Wei Liu
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Correspondence to Wei Liu or Jing Chen.

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Liu, W., Teng, Z., Li, Z. et al. CVGAE: A Self-Supervised Generative Method for Gene Regulatory Network Inference Using Single-Cell RNA Sequencing Data. Interdiscip Sci Comput Life Sci (2024). https://doi.org/10.1007/s12539-024-00633-y

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