SFINN: Inferring gene regulatory network from single-cell and spatial transcriptomic data with shared factor neighborhood and integrated neural network

Abstract

Motivation: The rise of single-cell RNA sequencing (scRNA-seq) technology presents new opportunities for constructing detailed cell type-specific gene regulatory networks (GRNs) to study cell heterogeneity. However, challenges caused by noises, technical errors, and dropout phenomena in scRNA-seq data pose significant obstacles to GRN inference, making the design of accurate GRN inference algorithms still essential. The recent growth of both single-cell and spatial transcriptomic sequencing data enables the development of supervised deep learning methods to infer GRNs on these diverse single-cell datasets. Results: In this study, we introduce a novel deep learning framework based on shared factor neighborhood and integrated neural network (SFINN) for inferring potential interactions and causalities between transcription factors and target genes from single-cell and spatial transcriptomic data. SFINN utilizes shared factor neighborhood to construct cellular neighborhood network based on gene expression data and additionally integrates cellular network generated from spatial location information. Subsequently, the cell adjacency matrix and gene pair expression are fed into an integrated neural network framework consisting of a graph convolutional neural network and a fully-connected neural network to determine whether the genes interact. Performance evaluation in the tasks of gene interaction and causality prediction against the existing GRN reconstruction algorithms demonstrates the usability and competitiveness of SFINN across different kinds of data. SFINN can be applied to infer GRNs from conventional single-cell sequencing data and spatial transcriptomic data.