title: Base resolution methylome profiling: considerations in platform selection, data preprocessing and analysis.
abstract: Bisulfite treatment-based methylation microarray (mainly Illumina 450K Infinium array) and next-generation sequencing (reduced representation bisulfite sequencing, Agilent SureSelect Human Methyl-Seq, NimbleGen SeqCap Epi CpGiant or whole-genome bisulfite sequencing) are commonly used for base resolution DNA methylome research. Although multiple tools and methods have been developed and used for the data preprocessing and analysis, confusions remains for these platforms including how and whether the 450k array should be normalized; which platform should be used to better fit researchers' needs; and which statistical models would be more appropriate for differential methylation analysis. This review presents the commonly used platforms and compares the pros and cons of each in methylome profiling. We then discuss approaches to study design, data normalization, bias correction and model selection for differentially methylated individual CpGs and regions.
authors.affiliation: Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Medical Genome Facility, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Cunningham
authors.affiliation: Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Slager
authors.affiliation: Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kocher
mesh_terms: D000465:Algorithms; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics / Q000379:methods*; D015894:Genome, Human / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D013447:Sulfites
chemical_list: D013447:Sulfites; D004247:DNA; C042345:hydrogen sulfite
keywords: DNA methylation; bisulfite sequencing; differential methylation; methylation 450K array; normalization; reduced representation bisulfite sequencing; study design