Dataset Information

Probe signal correction for differential methylation hybridization experiments.

ABSTRACT:

Background

Non-biological signal (or noise) has been the bane of microarray analysis. Hybridization effects related to probe-sequence composition and DNA dye-probe interactions have been observed in differential methylation hybridization (DMH) microarray experiments as well as other effects inherent to the DMH protocol.

Results

We suggest two models to correct for non-biologically relevant probe signal with an overarching focus on probe-sequence composition. The estimated effects are evaluated and the strengths of the models are considered in the context of DMH analyses.

Conclusion

The majority of estimated parameters were statistically significant in all considered models. Model selection for signal correction is based on interpretation of the estimated values and their biological significance.

SUBMITTER: Potter DP

PROVIDER: S-EPMC2603337 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Publications

Probe signal correction for differential methylation hybridization experiments.

Potter Dustin P DP Yan Pearlly P Huang Tim H M TH Lin Shili S

BMC bioinformatics 20081023

<h4>Background</h4>Non-biological signal (or noise) has been the bane of microarray analysis. Hybridization effects related to probe-sequence composition and DNA dye-probe interactions have been observed in differential methylation hybridization (DMH) microarray experiments as well as other effects inherent to the DMH protocol.<h4>Results</h4>We suggest two models to correct for non-biologically relevant probe signal with an overarching focus on probe-sequence composition. The estimated effects ...[more]

PMID: 18947421

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Project description:Cytosine methylation is an important DNA epigenetic modification. In vertebrates, methylation occurs at CpG sites, which are dinucleotides where a cytosine is immediately followed by a guanine in the DNA sequence from 5' to 3'. When located in the promoter region of a gene, DNA methylation is often associated with transcriptional silencing of the gene. Aberrant DNA methylation is associated with the development of various diseases such as cancer. Bisulfite sequencing (BS-seq) is the current "gold-standard" technology for high-resolution profiling of DNA methylation. Reduced representation bisulfite sequencing (RRBS) is an efficient form of BS-seq that targets CpG-rich DNA regions in order to save sequencing costs. A typical bioinformatics aim is to identify CpGs that are differentially methylated (DM) between experimental conditions. This workflow demonstrates that differential methylation analysis of RRBS data can be conducted using software and methodology originally developed for RNA-seq data. The RNA-seq pipeline is adapted to methylation by adding extra columns to the design matrix to account for read coverage at each CpG, after which the RRBS and RNA-seq pipelines are almost identical. This approach is statistically natural and gives analysts access to a rich collection of analysis tools including generalized linear models, gene set testing and pathway analysis. The article presents a complete start to finish case study analysis of RRBS profiles of different cell populations from the mouse mammary gland using the Bioconductor package edgeR. We show that lineage-committed cells are typically hyper-methylated compared to progenitor cells and this is true on all the autosomes but not the sex chromosomes. We demonstrate a strong negative correlation between methylation of promoter regions and gene expression as measured by RNA-seq for the same cell types, showing that methylation is a regulatory mechanism involved in epithelial linear commitment.

Dataset Information

Probe signal correction for differential methylation hybridization experiments.

Background

Results

Conclusion

Publications

Probe signal correction for differential methylation hybridization experiments.

Similar Datasets

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