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

Maria Giulia Bacalini; Alessio Boattini; Davide Gentilini; Enrico Giampieri; Chiara Pirazzini; Cristina Giuliani; Elisa Fontanesi; Daniel Remondini; Miriam Capri; Alberto Del Rio; Donata Luiselli; Giovanni Vitale; Daniela Mari; Gastone Castellani; Anna Maria Di Blasio; Stefano Salvioli; Claudio Franceschi; Paolo Garagnani

doi:doi:10.18632/aging.100718

Research Paper Volume 7, Issue 2 pp 97—109

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

Maria Giulia Bacalini^{oneuth1,2,3,

,}, Alessio Boattini^{oneuth4,

,}, Davide Gentilini^oneuth5,, Enrico Giampieri^oneuth6,, Chiara Pirazzini^oneuth1,2,, Cristina Giuliani^oneuth4,, Elisa Fontanesi^oneuth1,2,, Daniel Remondini^oneuth6,, Miriam Capri^oneuth1,2,, Alberto Del Rio^oneuth1,7,, Donata Luiselli^oneuth4,, Giovanni Vitale^oneuth5,8,, Daniela Mari^oneuth8,9,, Gastone Castellani^oneuth6,, Anna Maria Di Blasio^oneuth5,, Stefano Salvioli^oneuth1,2,, Claudio Franceschi^{oneuth1,2,10,}, Paolo Garagnani^{oneuth1,2,11,},

¹ Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
² Interdepartmental Center “L. Galvani”, University of Bologna, Bologna 40126, Italy
³ Personal Genomics S.r.l., Verona 37134, Italy
⁴ Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy
⁵ Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino 20095, Italy
⁶ Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy
⁷ Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy
⁸ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
⁹ Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
¹⁰ IRCCS Institute of Neurological Sciences, Bologna, Italy
¹¹ Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy

* Equal contribution

Received: December 23, 2014 Accepted: January 9, 2015 Published: January 11, 2015

https://doi.org/10.18632/aging.100718
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Bacalini MG, Boattini A, Gentilini D, Giampieri E, Pirazzini C, Giuliani C, Fontanesi E, Remondini D, Capri M, Del Rio A, Luiselli D, Vitale G, Mari D, et al, . A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data. Aging (Albany NY). 2015; 7:97-109. https://doi.org/10.18632/aging.100718

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Provider: 
        TY  - JOUR
        AU  - Bacalini, Maria Giulia 
        AU  - Boattini, Alessio 
        AU  - Gentilini, Davide 
        AU  - Giampieri, Enrico 
        AU  - Pirazzini, Chiara 
        AU  - Giuliani, Cristina 
        AU  - Fontanesi, Elisa 
        AU  - Remondini, Daniel 
        AU  - Capri, Miriam 
        AU  - Del Rio, Alberto 
        AU  - Luiselli, Donata 
        AU  - Vitale, Giovanni 
        AU  - Mari, Daniela 
        AU  - Castellani, Gastone 
        AU  - Di Blasio, Anna Maria 
        AU  - Salvioli, Stefano 
        AU  - Franceschi, Claudio 
        AU  - Garagnani, Paolo 
        TI  - A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 7
        IS  - 2
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.100718
        DO  - 10.18632/aging.100718
        SP  - 97
        EP  - 109
        PY  - 
        AB  - 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.
        ER  -

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This article has been corrected. See Correction. Aging (Albany NY). 2016; 8:831-831. https://doi.org/10.18632/aging.100915 PMID: 27182624

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.

Research Paper Volume 7, Issue 2 pp 97—109

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

Received: December 23, 2014 Accepted: January 9, 2015 Published: January 11, 2015

Abstract

Corresponding Author

Keywords