Journal Article

spliceJAC: transition genes and state‐specific gene regulation from single‐cell transcriptome data

Zhou, Peijie, Bocci, Federico, Nie, Qing

2022

Overview

Extracting dynamical information from single‐cell transcriptomics is a novel task with the promise to advance our understanding of cell state transition and interactions between genes. Yet, theory‐oriented, bottom‐up approaches that consider differences among cell states are largely lacking. Here, we present spliceJAC, a method to quantify the multivariate mRNA splicing from single‐cell RNA sequencing (scRNA‐seq). spliceJAC utilizes the unspliced and spliced mRNA count matrices to constructs cell state‐specific gene–gene regulatory interactions and applies stability analysis to predict putative driver genes critical to the transitions between cell states. By applying spliceJAC to biological systems including pancreas endothelium development and epithelial–mesenchymal transition (EMT) in A549 lung cancer cells, we predict genes that serve specific signaling roles in different cell states, recover important differentially expressed genes in agreement with pre‐existing analysis, and predict new transition genes that are either exclusive or shared between different cell state transitions. Synopsis spliceJAC builds a multivariate mRNA splicing model from single‐cell transcriptome data to infer the context‐specific gene regulation and the key driver genes that guide the transition between cell states. spliceJAC constructs cell state‐specific gene regulatory networks and quantifies changes in signaling roles between cell states. spliceJAC employs stability analysis to identify driver genes that guide transitions between cell states. Context‐specific gene regulation and transition genes are identified using spliceJAC during pancreas endothelium development and epithelial–mesenchymal transition (EMT) in A549 lung cancer cells. Graphical Abstract spliceJAC builds a multivariate mRNA splicing model from single‐cell transcriptome data to infer the context‐specific gene regulation and the key driver genes that guide the transition between cell states.

• Publisher: Nature Publishing Group UK,EMBO Press,John Wiley and Sons Inc,Springer Nature
• Subject: A549 Cells / attractor linear stability / cell state transition / EMBO10 / EMBO22 / Endothelium / Epithelial-Mesenchymal Transition - genetics / Gene expression / Gene Expression Regulation / Gene regulation / gene regulatory network / Gene sequencing / Genes / Humans / Lung cancer / Mesenchyme / mRNA splicing / Neurogenesis / Ordinary differential equations / RNA, Messenger - genetics / single‐cell RNA sequencing / Splicing / Stability analysis / Transcriptome / Transcriptomes / Transcriptomics