title: A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data.
abstract: Aging is characterized by a profound remodeling of the epigenetic architecture in terms of DNA methylation patterns. To date the most effective tool to study genome wide DNA methylation changes is Infinium HumanMethylation450 BeadChip (Infinium 450k). Despite the wealth of tools for Infinium 450k analysis, the identification of the most biologically relevant DNA methylation changes is still challenging. Here we propose an analytical pipeline to select differentially methylated regions (DMRs), tailored on microarray architecture, which is highly effective in highlighting biologically relevant results. The pipeline groups microarray probes on the basis of their localization respect to CpG islands and genic sequences and, depending on probes density, identifies DMRs through a single-probe or a region-centric approach that considers the concomitant variation of multiple adjacent CpG probes. We successfully applied this analytical pipeline on 3 independent Infinium 450k datasets that investigated age-associated changes in blood DNA methylation. We provide a consensus list of genes that systematically vary in DNA methylation levels from 0 to 100 years and that have a potentially relevant role in the aging process.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|Personal Genomics S.r.l., Verona 37134, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Boattini
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan 20095, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Giampieri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pirazzini
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fontanesi
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan 20095, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.|Geriatric Unit, IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.affiliation: Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy.
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.affiliation: Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Milan 20095, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Blasio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna 40138, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, Bologna 40126, Italy.|Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
mesh_terms: D000375:Aging / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis