DeepMAge: A Methylation Aging Clock Developed with Deep Learning

被引:76
作者
Galkin, Fedor [1 ,2 ]
Mamoshina, Polina [1 ]
Kochetov, Kirill [1 ]
Sidorenko, Denis [3 ]
Zhavoronkov, Alex [1 ,3 ,4 ]
机构
[1] Deep Longev Ltd, Hong Kong, Peoples R China
[2] Univ Liverpool, Inst Ageing & Chron Dis, Integrat Genom Ageing Grp, Liverpool, Merseyside, England
[3] Hong Kong Sci & Technol Pk, Insilico Med Hong Kong Ltd, Hong Kong, Peoples R China
[4] Buck Inst Res Aging, Novato, CA USA
关键词
aging; DNA methylation; epigenetics; artificial intelligence;
D O I
10.14336/AD.2020.1202
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
DNA methylation aging clocks have become an invaluable tool in biogerontology research since their inception in 2013. Today, a variety of machine learning approaches have been tested for the purpose of predicting human age based on molecular-level features. Among these, deep learning, or neural networks, is an especially promising approach that has been used to construct accurate clocks using blood biochemistry, transcriptomics, and microbiomics data-feats unachieved by other algorithms. In this article, we explore how deep learning performs in a DNA methylation setting and compare it to the current industry standard-the 353 CpG clock published in 2013. The aging clock we are presenting (DeepMAge) is a neural network regressor trained on 4,930 blood DNA methylation profiles from 17 studies. Its absolute median error was 2.77 years in an independent verification set of 1,293 samples from 15 studies. DeepMAge shows biological relevance by assigning a higher predicted age to people with various health-related conditions, such as ovarian cancer, irritable bowel diseases, and multiple sclerosis.
引用
收藏
页码:1252 / 1262
页数:11
相关论文
共 27 条
[1]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[2]   Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing? [J].
Belsky, Daniel W. ;
Moffitt, Terrie E. ;
Cohen, Alan A. ;
Corcoran, David L. ;
Levine, Morgan E. ;
Prinz, Joseph A. ;
Schaefer, Jonathan ;
Sugden, Karen ;
Williams, Benjamin ;
Poulton, Richie ;
Caspi, Avshalom .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2018, 187 (06) :1220-1230
[3]   lumi:: a pipeline for processing Illumina microarray [J].
Du, Pan ;
Kibbe, Warren A. ;
Lin, Simon M. .
BIOINFORMATICS, 2008, 24 (13) :1547-1548
[4]   Human Gut Microbiome Aging Clock Based on Taxonomic Profiling and Deep Learning [J].
Galkin, Fedor ;
Mamoshina, Polina ;
Aliper, Alex ;
Putin, Evgeny ;
Moskalev, Vladimir ;
Gladyshev, Vadim N. ;
Zhavoronkov, Alex .
ISCIENCE, 2020, 23 (06)
[5]   Biohorology and biomarkers of aging: Current state-of-the-art, challenges and opportunities [J].
Galkin, Fedor ;
Mamoshina, Polina ;
Aliper, Alex ;
de Magalhaes, Joao Pedro ;
Gladyshev, Vadim N. ;
Zhavoronkov, Alex .
AGEING RESEARCH REVIEWS, 2020, 60
[6]   Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates [J].
Hannum, Gregory ;
Guinney, Justin ;
Zhao, Ling ;
Zhang, Li ;
Hughes, Guy ;
Sadda, SriniVas ;
Klotzle, Brandy ;
Bibikova, Marina ;
Fan, Jian-Bing ;
Gao, Yuan ;
Deconde, Rob ;
Chen, Menzies ;
Rajapakse, Indika ;
Friend, Stephen ;
Ideker, Trey ;
Zhang, Kang .
MOLECULAR CELL, 2013, 49 (02) :359-367
[7]   DNA methylation-based biomarkers and the epigenetic clock theory of ageing [J].
Horvath, Steve ;
Raj, Kenneth .
NATURE REVIEWS GENETICS, 2018, 19 (06) :371-384
[8]   DNA methylation age of human tissues and cell types [J].
Horvath, Steve .
GENOME BIOLOGY, 2013, 14 (10)
[9]   The Prognostic Significance of Quantitative Myocardial Perfusion An Artificial Intelligence-Based Approach Using Perfusion Mapping [J].
Knott, Kristopher D. ;
Seraphim, Andreas ;
Augusto, Joao B. ;
Xue, Hui ;
Chacko, Liza ;
Aung, Nay ;
Petersen, Steffen E. ;
Cooper, Jackie A. ;
Manisty, Charlotte ;
Bhuva, Anish N. ;
Kotecha, Tushar ;
Bourantas, Christos V. ;
Davies, Rhodri H. ;
Brown, Louise A. E. ;
Plein, Sven ;
Fontana, Marianna ;
Kellman, Peter ;
Moon, James C. .
CIRCULATION, 2020, 141 (16) :1282-1291
[10]   Feature Selection With Neural Networks [J].
Philippe Leray ;
Patrick Gallinari .
Behaviormetrika, 1999, 26 (1) :145-166