A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data

作者:Bacalini Maria Giulia; Boattini Alessio; Gentilini Davide; Giampieri Enrico; Pirazzini Chiara; Giuliani Cristina; Fontanesi Elisa; Remondini Daniel; Capri Miriam; Del Rio Alberto; Luiselli Donata; Vitale Giovanni; Mari Daniela; Castellani Gastone; Di Blasio Anna Maria; Salvioli Stefano; Franceschi Claudio*; Garagnani Paolo
来源:Aging-US, 2015, 7(2): 97-109.
DOI:10.18632/aging.100718

摘要

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.

  • 出版日期2015-2