title: PrEMeR-CG: inferring nucleotide level DNA methylation values from MethylCap-seq data.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Frankhouser
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Murphy
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Blachly
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jincheol
authors.initials: J
authors.lastname: Park
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mike W
authors.initials: MW
authors.lastname: Zoller
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Javkhlan-Ochir
authors.initials: JO
authors.lastname: Ganbat
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: John
authors.initials: J
authors.lastname: Curfman
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Shili
authors.initials: S
authors.lastname: Lin
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Pearlly
authors.initials: P
authors.lastname: Yan
authors.affiliation: College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA College of Medicine, Biomedical Sciences Graduate Program, Department of Internal Medicine, Division of Hematology, Department of Statistics, Mathematical Biosciences Institute, Department of Physics, Department of Chemistry & Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bundschuh
mesh_terms: D000465:Algorithms; D018899:CpG Islands; D019175:DNA Methylation; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D009711:Nucleotides / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D013447:Sulfites
chemical_list: D009711:Nucleotides; D013447:Sulfites; C042345:hydrogen sulfite