Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions.
BACKGROUND
Epigenetics is the study of heritable changes in gene function that cannot be explained by changes in DNA sequence. One of the most commonly studied epigenetic alterations is cytosine methylation, which is a well recognized mechanism of epigenetic gene silencing and often occurs at tumor suppressor gene loci in human cancer. Arrays are now being used to study DNA methylation at a large number of loci; for example, the Illumina GoldenGate platform assesses DNA methylation at 1505 loci associated with over 800 cancer-related genes. Model-based cluster analysis is often used to identify DNA methylation subgroups in data, but it is unclear how to cluster DNA methylation data from arrays in a scalable and reliable manner.


RESULTS
We propose a novel model-based recursive-partitioning algorithm to navigate clusters in a beta mixture model. We present simulations that show that the method is more reliable than competing nonparametric clustering approaches, and is at least as reliable as conventional mixture model methods. We also show that our proposed method is more computationally efficient than conventional mixture model approaches. We demonstrate our method on the normal tissue samples and show that the clusters are associated with tissue type as well as age.


CONCLUSIONS
Our proposed recursively-partitioned mixture model is an effective and computationally efficient method for clustering DNA methylation data.
Houseman
E Andres
EA
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, 02115, USA. ahousema@hsph.harvard.edu
Christensen
Brock C
BC
Yeh
Ru-Fang
RF
Marsit
Carmen J
CJ
Karagas
Margaret R
MR
Wrensch
Margaret
M
Nelson
Heather H
HH
Wiemels
Joseph
J
Zheng
Shichun
S
Wiencke
John K
JK
Kelsey
Karl T
KT
D000465:Algorithms; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods; D016000:Cluster Analysis; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated / Q000379:methods; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*
D004247:DNA
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