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

Fernández M, Miranda-Saavedra D - Nucleic Acids Res. (2012)

Bottom Line: 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 indicate that ChromaGenSVM comfortably outperforms previously published methods and that enhancers are best predicted by specific combinations of histone methylation and acetylation marks.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Genomics Laboratory, WPI-Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita 565-0871, Osaka, Japan.

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 indicate that ChromaGenSVM comfortably outperforms previously published methods and that enhancers are best predicted by specific combinations of histone methylation and acetylation marks.

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Cross-validation ROC plot of the optimum SVM model to predict enhancers in human CD4+ T cells using the histone modification maps H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac.
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gks149-F7: Cross-validation ROC plot of the optimum SVM model to predict enhancers in human CD4+ T cells using the histone modification maps H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac.

Mentions: Figure 7 depicts the ROC of the optimum SVM model generated by ChromaGenSVM that recognizes enhancers in human CD4+ T cells with an AUC, specificity and sensitivity of 0.975, 0.935 and 0.966, respectively, and a maximum F-score of 0.950. This predictor was trained with three methylations and two acetylations marks computed at 1.0 kb windows: H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac. The optimum Gaussian kernel has a shift parameter of 400 bp. This optimum combination of methylation and acetylation marks includes two of the most frequent marks (H2BK5Ac, H3K4Me3) accompanied by two other methylation marks (H3K4Me1, H3R2Me2) that complement the epigenetic landscape at TSS distal regulatory regions along with another acetylation mark (H4K8Ac).Figure 7.


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

Fernández M, Miranda-Saavedra D - Nucleic Acids Res. (2012)

Cross-validation ROC plot of the optimum SVM model to predict enhancers in human CD4+ T cells using the histone modification maps H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378905&req=5

gks149-F7: Cross-validation ROC plot of the optimum SVM model to predict enhancers in human CD4+ T cells using the histone modification maps H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac.
Mentions: Figure 7 depicts the ROC of the optimum SVM model generated by ChromaGenSVM that recognizes enhancers in human CD4+ T cells with an AUC, specificity and sensitivity of 0.975, 0.935 and 0.966, respectively, and a maximum F-score of 0.950. This predictor was trained with three methylations and two acetylations marks computed at 1.0 kb windows: H3K4Me1, H3K4Me3, H3R2Me2, H4K8Ac and H2BK5Ac. The optimum Gaussian kernel has a shift parameter of 400 bp. This optimum combination of methylation and acetylation marks includes two of the most frequent marks (H2BK5Ac, H3K4Me3) accompanied by two other methylation marks (H3K4Me1, H3R2Me2) that complement the epigenetic landscape at TSS distal regulatory regions along with another acetylation mark (H4K8Ac).Figure 7.

Bottom Line: 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 indicate that ChromaGenSVM comfortably outperforms previously published methods and that enhancers are best predicted by specific combinations of histone methylation and acetylation marks.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Genomics Laboratory, WPI-Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita 565-0871, Osaka, Japan.

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 indicate that ChromaGenSVM comfortably outperforms previously published methods and that enhancers are best predicted by specific combinations of histone methylation and acetylation marks.

Show MeSH
Related in: MedlinePlus