A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis.
DNA methylation is an indispensible epigenetic modification required for regulating the expression of mammalian genomes. Immunoprecipitation-based methods for DNA methylome analysis are rapidly shifting the bottleneck in this field from data generation to data analysis, necessitating the development of better analytical tools. In particular, an inability to estimate absolute methylation levels remains a major analytical difficulty associated with immunoprecipitation-based DNA methylation profiling. To address this issue, we developed a cross-platform algorithm-Bayesian tool for methylation analysis (Batman)-for analyzing methylated DNA immunoprecipitation (MeDIP) profiles generated using oligonucleotide arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). We developed the latter approach to provide a high-resolution whole-genome DNA methylation profile (DNA methylome) of a mammalian genome. Strong correlation of our data, obtained using mature human spermatozoa, with those obtained using bisulfite sequencing suggest that combining MeDIP-seq or MeDIP-chip with Batman provides a robust, quantitative and cost-effective functional genomic strategy for elucidating the function of DNA methylation.
Down
Thomas A
TA
Wellcome Trust Cancer Research UK Gurdon Institute, and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. thomas.down@gurdon.cam.ac.uk
Rakyan
Vardhman K
VK
Turner
Daniel J
DJ
Flicek
Paul
P
Li
Heng
H
Kulesha
Eugene
E
Gräf
Stefan
S
Johnson
Nathan
N
Herrero
Javier
J
Tomazou
Eleni M
EM
Thorne
Natalie P
NP
Bäckdahl
Liselotte
L
Herberth
Marlis
M
Howe
Kevin L
KL
Jackson
David K
DK
Miretti
Marcos M
MM
Marioni
John C
JC
Birney
Ewan
E
Hubbard
Tim J P
TJ
Durbin
Richard
R
Tavaré
Simon
S
Beck
Stephan
S
D000465:Algorithms; D001483:Base Sequence; D001499:Bayes Theorem; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*
D004247:DNA