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

被引:18
作者
Bocci, Federico [1 ,2 ]
Zhou, Peijie [1 ]
Nie, Qing [1 ,2 ,3 ]
机构
[1] Univ Calif Irvine, Dept Math, Irvine, CA 92717 USA
[2] Univ Calif Irvine, NSF Simons Ctr Multiscale Cell Fate Res, Irvine, CA 92717 USA
[3] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
attractor linear stability; cell state transition; gene regulatory network; mRNA splicing; single-cell RNA sequencing; INFERENCE; NETWORKS; EMT; LANDSCAPE; TIME;
D O I
10.15252/msb.202211176
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:15
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