Introduction

DNA methylation is an epigenetic change occurring in genomic CpG sequences that contribute to the regulation of gene transcription both in normal and malignant cells. Next-generation sequencing has been used to characterize DNA methylation status at the genome scale, but suffers from high sequencing cost in the case of whole-genome bisulfite sequencing, or from reduced resolution (inability to precisely define which of the CpGs are methylated) with capture-based techniques.Here we present a computational method that computes nucleotide-resolution methylation values from capture-based data by incorporating fragment length profiles into a model of methylation analysis. We demonstrate that it compares favorably with nucleotide-resolution bisulfite sequencing and has better predictive power with respect to a reference than window-based methods, often used for enrichment data. The described method was used to produce the methylation data used in tandem with gene expression to produce a novel and clinically significant gene signature in acute myeloid leukemia. In addition, we introduce a complementary statistical method that uses this nucleotide-resolution methylation data for detection of differentially methylated features.

Publications

  1. PrEMeR-CG: inferring nucleotide level DNA methylation values from MethylCap-seq data.
    Cite this
    Frankhouser DE, Murphy M, Blachly JS, Park J, Zoller MW, Ganbat JO, Curfman J, Byrd JC, Lin S, Marcucci G, Yan P, Bundschuh R, 2014-12-01 - Bioinformatics (Oxford, England)

Credits

  1. David E Frankhouser
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  2. Mark Murphy
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  3. James S Blachly
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  4. Jincheol Park
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  5. Mike W Zoller
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  6. Javkhlan-Ochir Ganbat
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  7. John Curfman
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  8. John C Byrd
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  9. Shili Lin
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  10. Guido Marcucci
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  11. Pearlly Yan
    Developer

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

  12. Ralf Bundschuh
    Investigator

    College of Medicine, Biomedical Sciences Graduate Program, United States of America

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Summary
AccessionBT000110
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesR
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByRalf Bundschuh