Joint learning of multiple gene networks from single-cell gene expression data

Abstract

Inferring gene networks from gene expression data is important for understanding functional organizations within cells. With the accumulation of single-cell RNA sequencing (scRNA-seq) data, it is possible to infer gene networks at single cell level. However, due to the characteristics of scRNA-seq data, such as cellular heterogeneity and high sparsity caused by dropout events, traditional network inference methods may not be suitable for scRNA-seq data. In this study, we introduce a novel joint Gaussian copula graphical model (JGCGM) to jointly estimate multiple gene networks for multiple cell subgroups from scRNA-seq data. Our model can deal with non-Gaussian data with missing values, and identify the common and unique network structures of multiple cell subgroups, which is suitable for scRNA-seq data. Extensive experiments on synthetic data demonstrate that our proposed model outperforms other compared state-of-the-art network inference models. We apply our model to real scRNA-seq data sets to infer gene networks of different cell subgroups. Hub genes in the estimated gene networks are found to be biological significance.