cisTopic: cis-regulatory topic modeling on single-cell ATAC-seq data

被引:239
作者
Gonzalez-Blas, Carmen Bravo [1 ,2 ]
Minnoye, Liesbeth [1 ,2 ]
Papasokrati, Dafni [1 ,2 ]
Aibar, Sara [1 ,2 ]
Hulselmans, Gert [1 ,2 ]
Christiaens, Valerie [1 ,2 ]
Davie, Kristofer [1 ,2 ]
Wouters, Jasper [1 ,2 ]
Aerts, Stein [1 ,2 ]
机构
[1] VIB Ctr Brain & Dis Res, Leuven, Belgium
[2] Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium
关键词
CHROMATIN ACCESSIBILITY; PACKAGE; INFERENCE; CLUSTERS; ELEMENTS; TOUCAN; MOUSE;
D O I
10.1038/s41592-019-0367-1
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We present cisTopic, a probabilistic framework used to simultaneously discover coaccessible enhancers and stable cell states from sparse single-cell epigenomics data (http://github.com/aertslab/cistopic). Using a compendium of single-cell ATAC-seq datasets from differentiating hematopoietic cells, brain and transcription factor perturbations, we demonstrate that topic modeling can be exploited for robust identification of cell types, enhancers and relevant transcription factors. cisTopic provides insight into the mechanisms underlying regulatory heterogeneity in cell populations.
引用
收藏
页码:397 / +
页数:8
相关论文
共 58 条
[1]   TOUCAN 2: the all-inclusive open source workbench for regulatory sequence analysis [J].
Aerts, S ;
Van Loo, P ;
Thijs, G ;
Mayer, H ;
de Martin, R ;
Moreau, Y ;
De Moor, B .
NUCLEIC ACIDS RESEARCH, 2005, 33 :W393-W396
[2]   Toucan:: deciphering the cis-regulatory logic of coregulated genes [J].
Aerts, S ;
Thijs, G ;
Coessens, B ;
Staes, M ;
Moreau, Y ;
Moor, BD .
NUCLEIC ACIDS RESEARCH, 2003, 31 (06) :1753-1764
[3]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/nmeth.4463, 10.1038/NMETH.4463]
[4]   destiny: diffusion maps for large-scale single cell data in R [J].
Angerer, Philipp ;
Haghverdi, Laleh ;
Buettner, Maren ;
Theis, Fabian J. ;
Marr, Carsten ;
Buettner, Florian .
BIOINFORMATICS, 2016, 32 (08) :1241-1243
[5]   LEVELS OF DOPACHROME TAUTOMERASE IN HUMAN MELANOCYTES CULTURED IN-VITRO [J].
BERND, A ;
RAMIREZBOSCA, A ;
KIPPENBERGER, S ;
MARTINEZLIARTE, JH ;
HOLZMANN, H ;
SOLANO, F .
MELANOMA RESEARCH, 1994, 4 (05) :287-291
[6]   Latent Dirichlet allocation [J].
Blei, DM ;
Ng, AY ;
Jordan, MI .
JOURNAL OF MACHINE LEARNING RESEARCH, 2003, 3 (4-5) :993-1022
[7]  
Buac K., 2011, PIGM CELL MELANOMA R, V22, P773
[8]   Single-cell chromatin accessibility reveals principles of regulatory variation [J].
Buenostro, Jason D. ;
Wu, Beijing ;
Litzenburger, Ulrike M. ;
Ruff, Dave ;
Gonzales, Michael L. ;
Snyder, Michael P. ;
Chang, Howard Y. ;
Greenleaf, William J. .
NATURE, 2015, 523 (7561) :486-U264
[9]   Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation [J].
Buenrostro, Jason D. ;
Corces, M. Ryan ;
Lareau, Caleb A. ;
Wu, Beijing ;
Schep, Alicia N. ;
Aryee, Martin J. ;
Majeti, Ravindra ;
Chang, Howard Y. ;
Greenleaf, William J. .
CELL, 2018, 173 (06) :1535-+
[10]  
Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]