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2015 ; 16
(1
): 14
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Predicting genome-wide DNA methylation using methylation marks, genomic position,
and DNA regulatory elements
#MMPMID25616342
Zhang W
; Spector TD
; Deloukas P
; Bell JT
; Engelhardt BE
Genome Biol
2015[Jan]; 16
(1
): 14
PMID25616342
show ga
BACKGROUND: Recent assays for individual-specific genome-wide DNA methylation
profiles have enabled epigenome-wide association studies to identify specific CpG
sites associated with a phenotype. Computational prediction of CpG site-specific
methylation levels is critical to enable genome-wide analyses, but current
approaches tackle average methylation within a locus and are often limited to
specific genomic regions. RESULTS: We characterize genome-wide DNA methylation
patterns, and show that correlation among CpG sites decays rapidly, making
predictions solely based on neighboring sites challenging. We built a random
forest classifier to predict methylation levels at CpG site resolution using
features including neighboring CpG site methylation levels and genomic distance,
co-localization with coding regions, CpG islands (CGIs), and regulatory elements
from the ENCODE project. Our approach achieves 92% prediction accuracy of
genome-wide methylation levels at single-CpG-site precision. The accuracy
increases to 98% when restricted to CpG sites within CGIs and is robust across
platform and cell-type heterogeneity. Our classifier outperforms other types of
classifiers and identifies features that contribute to prediction accuracy:
neighboring CpG site methylation, CGIs, co-localized DNase I hypersensitive
sites, transcription factor binding sites, and histone modifications were found
to be most predictive of methylation levels. CONCLUSIONS: Our observations of DNA
methylation patterns led us to develop a classifier to predict DNA methylation
levels at CpG site resolution with high accuracy. Furthermore, our method
identified genomic features that interact with DNA methylation, suggesting
mechanisms involved in DNA methylation modification and regulation, and linking
diverse epigenetic processes.