Revealing dynamics of gene expression variability in cell state space

被引:51
作者
Gruen, Dominic [1 ,2 ]
机构
[1] Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany
[2] Univ Freiburg, Ctr Integrat Biol Signaling Studies, Freiburg, Germany
基金
欧洲研究理事会;
关键词
NOISE;
D O I
10.1038/s41592-019-0632-3
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
VarID is a computational method that quantifies the dynamics of transcriptional variability with the goal of identifying the role of highly variable genes, such as weakly expressed transcription factors, in cell differentiation or state transitions. To decipher cell state transitions from single-cell transcriptomes it is crucial to quantify weak expression of lineage-determining factors, which requires computational methods that are sensitive to the variability of weakly expressed genes. Here, I introduce VarID, a computational method that identifies locally homogenous neighborhoods in cell state space, permitting the quantification of local variability in gene expression. VarID delineates neighborhoods with differential gene expression variability and reveals pseudo-temporal dynamics of variability during differentiation.
引用
收藏
页码:45 / +
页数:7
相关论文
共 24 条
  • [1] Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/NMETH.4463, 10.1038/nmeth.4463]
  • [2] Differential expression analysis for sequence count data
    Anders, Simon
    Huber, Wolfgang
    [J]. GENOME BIOLOGY, 2010, 11 (10):
  • [3] Brennecke P, 2013, NAT METHODS, V10, P1093, DOI [10.1038/NMETH.2645, 10.1038/nmeth.2645]
  • [4] Doi Y, 2015, BLOOD, V126
  • [5] Correcting the Mean-Variance Dependency for Differential Variability Testing Using Single-Cell RNA Sequencing Data
    Eling, Nils
    Richard, Arianne C.
    Richardson, Sylvia
    Marioni, John C.
    Vallejos, Catalina A.
    [J]. CELL SYSTEMS, 2018, 7 (03) : 284 - +
  • [6] Grun Dominic, 2018, Current Opinion in Systems Biology, V11, P9, DOI 10.1016/j.coisb.2018.07.006
  • [7] Single-cell messenger RNA sequencing reveals rare intestinal cell types
    Grun, Dominic
    Lyubimova, Anna
    Kester, Lennart
    Wiebrands, Kay
    Basak, Onur
    Sasaki, Nobuo
    Clevers, Hans
    van Oudenaarden, Alexander
    [J]. NATURE, 2015, 525 (7568) : 251 - +
  • [8] Grün D, 2014, NAT METHODS, V11, P637, DOI [10.1038/NMETH.2930, 10.1038/nmeth.2930]
  • [9] A single-cell survey of the small intestinal epithelium
    Haber, Adam L.
    Biton, Moshe
    Rogel, Noga
    Herbst, Rebecca H.
    Shekhar, Karthik
    Smillie, Christopher
    Burgin, Grace
    Delorey, Toni M.
    Howitt, Michael R.
    Katz, Yarden
    Tirosh, Itay
    Beyaz, Semir
    Dionne, Danielle
    Zhang, Mei
    Raychowdhury, Raktima
    Garrett, Wendy S.
    Rozenblatt-Rosen, Orit
    Shi, Hai Ning
    Yilmaz, Omer
    Xavier, Ramnik J.
    Regev, Aviv
    [J]. NATURE, 2017, 551 (7680) : 333 - +
  • [10] Hafemeister C, 2019, Genome biology