Introduction

The ability to assay genome-scale methylation patterns using high-throughput sequencing makes it possible to carry out association studies to determine the relationship between epigenetic variation and phenotype. While bisulfite sequencing can determine a methylome at high resolution, cost inhibits its use in comparative and population studies. MethylSeq, based on sequencing of fragment ends produced by a methylation-sensitive restriction enzyme, is a method for methyltyping (survey of methylation states) and is a site-specific and cost-effective alternative to whole-genome bisulfite sequencing. Despite its advantages, the use of MethylSeq has been restricted by biases in MethylSeq data that complicate the determination of methyltypes. Here we introduce a statistical method, MetMap, that produces corrected site-specific methylation states from MethylSeq experiments and annotates unmethylated islands across the genome. MetMap integrates genome sequence information with experimental data, in a statistically sound and cohesive Bayesian Network. It infers the extent of methylation at individual CGs and across regions, and serves as a framework for comparative methylation analysis within and among species. We validated MetMap's inferences with direct bisulfite sequencing, showing that the methylation status of sites and islands is accurately inferred. We used MetMap to analyze MethylSeq data from four human neutrophil samples, identifying novel, highly unmethylated islands that are invisible to sequence-based annotation strategies. The combination of MethylSeq and MetMap is a powerful and cost-effective tool for determining genome-scale methyltypes suitable for comparative and association studies.

Publications

  1. MetMap enables genome-scale Methyltyping for determining methylation states in populations.
    Cite this
    Singer M, Boffelli D, Dhahbi J, Schönhuth A, Schroth GP, Martin DI, Pachter L, 2010-08-01 - PLoS computational biology

Credits

  1. Meromit Singer
    Developer

    Computer Science Division, University of California at Berkeley, United States of America

  2. Dario Boffelli
    Developer

  3. Joseph Dhahbi
    Developer

  4. Alexander Schönhuth
    Developer

  5. Gary P Schroth
    Developer

  6. David I K Martin
    Developer

  7. Lior Pachter
    Investigator

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Summary
AccessionBT006465
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByLior Pachter