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Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
Published on: February 24, 2015
FadE: whole genome methylation analysis for multiple sequencing platforms
Tade Souaiaia1, Zheng Zhang, Ting Chen
1Program in Computational Biology and Bioinformatics, University of Southern California, 1050 Childs Way, RRI 201, Los Angeles, CA 90089, USA.
Nucleic Acids Research
|September 12, 2012
Summary
FadE accurately determines genome-wide DNA methylation rates from sequencing data, even with errors. This new algorithm improves analysis of methylation patterns in genomic regulation and disease research.
Area of Science:
- Genomics
- Epigenetics
- Bioinformatics
Background:
- DNA methylation is crucial for genomic regulation and disease.
- Sodium bisulfite treatment (SBT) is a standard method to assess DNA methylation.
- SOLiD sequencer color reads present challenges for accurate methylation analysis due to sequencing errors.
Purpose of the Study:
- To develop an algorithm (FadE) for accurate genome-wide DNA methylation rate determination.
- To enable reliable methylation analysis directly from SOLiD sequencer color or nucleotide reads.
- To investigate genome-wide methylation levels in human fibroblasts.
Main Methods:
- Developed FadE algorithm incorporating background error rates from SBT untreated data.
- Utilized Newton-Raphson optimization to estimate methylation rates and credible intervals.
- Sequenced human fibroblast cell-line bisulfite-converted fragment libraries using SOLiD sequencer.
Main Results:
- FadE accurately estimates genome-wide methylation rates from color or nucleotide reads.
- Identified widespread differences in methylation across CpG islands.
- Detected numerous differentially methylated regions adjacent to genes.
Conclusions:
- FadE provides an accurate method for genome-wide methylation estimation.
- The algorithm performs favorably compared to nucleotide-space analysis at higher coverage.
- FadE enhances the study of genomic regulation and disease through improved methylation analysis.
