DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning

被引:304
作者
Angermueller, Christof [1 ]
Lee, Heather J. [2 ,3 ]
Reik, Wolf [2 ,3 ]
Stegle, Oliver [1 ]
机构
[1] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England
[2] Babraham Inst, Epigenet Programme, Cambridge, England
[3] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England
来源
GENOME BIOLOGY | 2017年 / 18卷
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
Deep learning; Artificial neural network; Machine learning; Single-cell genomics; DNA methylation; Epigenetics; EMBRYONIC STEM-CELLS; SEQUENCE; SITES; DIFFERENTIATION; HEXANUCLEOTIDE; VERTEBRATE; LANDSCAPES; INFERENCE; CHROMATIN; VARIANTS;
D O I
10.1186/s13059-017-1189-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Recent technological advances have enabled DNA methylation to be assayed at single-cell resolution. However, current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. We report DeepCpG, a computational approach based on deep neural networks to predict methylation states in single cells. We evaluate DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols. DeepCpG yields substantially more accurate predictions than previous methods. Additionally, we show that the model parameters can be interpreted, thereby providing insights into how sequence composition affects methylation variability.
引用
收藏
页数:13
相关论文
共 72 条
[51]   In Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control Regions [J].
Quenneville, Simon ;
Verde, Gaetano ;
Corsinotti, Andrea ;
Kapopoulou, Adamandia ;
Jakobsson, Johan ;
Offner, Sandra ;
Baglivo, Ilaria ;
Pedone, Paolo V. ;
Grimaldi, Giovanna ;
Riccio, Andrea ;
Trono, Didier .
MOLECULAR CELL, 2011, 44 (03) :361-372
[52]   DNA methylation and human disease [J].
Robertson, KD .
NATURE REVIEWS GENETICS, 2005, 6 (08) :597-610
[53]   Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes [J].
Siepel, A ;
Bejerano, G ;
Pedersen, JS ;
Hinrichs, AS ;
Hou, MM ;
Rosenbloom, K ;
Clawson, H ;
Spieth, J ;
Hillier, LW ;
Richards, S ;
Weinstock, GM ;
Wilson, RK ;
Gibbs, RA ;
Kent, WJ ;
Miller, W ;
Haussler, D .
GENOME RESEARCH, 2005, 15 (08) :1034-1050
[54]  
Simonyan K., 2014, INT C LEARN REPR WOR
[55]   On counting position weight matrix matches in a sequence, with application to discriminative motif finding [J].
Sinha, Saurabh .
BIOINFORMATICS, 2006, 22 (14) :E454-E463
[56]  
Smallwood SA, 2014, NAT METHODS, V11, P817, DOI [10.1038/NMETH.3035, 10.1038/nmeth.3035]
[57]  
Srivastava N, 2014, J MACH LEARN RES, V15, P1929
[58]   Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods [J].
Stevens, Michael ;
Cheng, Jeffrey B. ;
Li, Daofeng ;
Xie, Mingchao ;
Hong, Chibo ;
Maire, Cecile L. ;
Ligon, Keith L. ;
Hirst, Martin ;
Marra, Marco A. ;
Costello, Joseph F. ;
Wang, Ting .
GENOME RESEARCH, 2013, 23 (09) :1541-1553
[59]   USE OF THE PERCEPTRON ALGORITHM TO DISTINGUISH TRANSLATIONAL INITIATION SITES IN ESCHERICHIA-COLI [J].
STORMO, GD ;
SCHNEIDER, TD ;
GOLD, L ;
EHRENFEUCHT, A .
NUCLEIC ACIDS RESEARCH, 1982, 10 (09) :2997-3011
[60]   HMG20A and HMG20B map to human chromosomes 15q24 and 19p13.3 and constitute a distinct class of HMG-box genes with ubiquitous expression [J].
Sumoy, L ;
Carim, L ;
Escarceller, M ;
Nadal, M ;
Gratacòs, M ;
Pujana, MA ;
Estivill, X ;
Peral, B .
CYTOGENETICS AND CELL GENETICS, 2000, 88 (1-2) :62-67