Genome-wide enhancer prediction from epigenetic signatures using genetic algorithm-optimized support vector machines.

Nucleic Acids Research
Michael Fernández, Diego Miranda-Saavedra

Abstract

The chemical modification of histones at specific DNA regulatory elements is linked to the activation, inactivation and poising of genes. A number of tools exist to predict enhancers from chromatin modification maps, but their practical application is limited because they either (i) consider a smaller number of marks than those necessary to define the various enhancer classes or (ii) work with an excessive number of marks, which is experimentally unviable. We have developed a method for chromatin state detection using support vector machines in combination with genetic algorithm optimization, called ChromaGenSVM. ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. In an independent test, ChromaGenSVM recovered 88% of the experimentally supported enhancers in the pilot ENCODE region of interferon gamma-treated HeLa cells. Furthermore, ChromaGenSVM successfully combined the profiles of only five distinct methylation and acetylation marks from ChIP-seq libraries done in human CD4(+) T cells to predict ∼21,000 experimentally supported enhancers within 1.0 kb regions and with a precision of ∼90%, thereby improving previous predictions on the same dataset by 21%. The combined results i...Continue Reading

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Methods Mentioned

BETA
electrophoretic mobility shift
ChIP-chip
acetylation
ChIP-seq
acetylations
histone acetylation
chemical modification
feature extraction
histone acetylations

Software Mentioned

GA
PReMod
HMM
ChromaGenSVM
SHOGUN
SICER
GREAT
PhastCons
Pyevolve
ANN

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