INVESTIGATION
Infinium Monkeys: Infinium 450K Array for the
Cynomolgus macaque (Macaca fascicularis)
Mei-Lyn Ong,* Peck Yean Tan,* Julia L MacIsaac,
†
Sarah M Mah,
†
Jan Paul Buschdorf,* Clara Y Cheong,*
Walter Stunkel,* Louiza Chan,* Peter D. Gluckman,* Keefe Chng,* Michael S. Kobor,
†
Michael J Meaney,*
,‡
and Joanna D Holbrook*
,1
*Singapore Institute of Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore 117609,
†
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia,
Canada, and
‡
Ludmer Centre for Neuroinformatics and Mental Health, Douglas Institute, McGill University, Montreal,
Canada
ABSTRACT The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-
efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is
an important disease model; however, its genome sequence is only recently published, and few tools exist
to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybrid-
ization array designed to the human genome, the relative conservation between the macaque and human
genomes makes its use in macaques feasible. Here, we used the Infinium 450K array to assay DNA meth-
ylation in 11 macaque muscle biopsies. We showed that probe hybridization efficiency was related to the
degree of sequence identity between the human probes and the macaque genome sequence. Approxi-
mately 61% of the Human Infinium 450K probes could be reliably mapped to the Cynomolgus macaque
genome and contain a CpG site of interest. We also compared the Infinium 450K data to reduced repre-
sentation bisulfite sequencing data generated on the same samples and found a high level of concordance
between the two independent methodologies, which can be further improved by filtering for probe se-
quence identity and mismatch location. We conclude that the Infinium 450K array can be used to measure
the DNA methylome of Cynomolgus macaque tissues using the provided filters. We also provide a pipeline
for validation of the array in other species using a simple BLAST-based sequence identify filter.
KEYWORDS
epigenetics
DNA methylation
nonhuman
primates
disease model
cynomolgus
macaque
Macaca fascularis
Illumina Infinium
Human
Methylation450
BeadChip Array
Biomedical research relies on nonhuman primate models, including
the Cynomolgus macaque. Cynomolgus models are used to investigate
diseases as diverse as Parkinson (Grabli et al. 2013; Potts et al. 2014;
Riverol et al. 2013), influenza (Kobayashi et al. 2013; Pham et al.
2013), asthma (Cheng et al. 2013), diabetes (Kaplan and Wagner
2006), and atherosclerosis (Clarkson et al. 2013; Kaplan et al. 1996).
However, the genome of this important model only was elucidated
recently (Higashino et al. 2012; Yan et al. 2011), and tools for ge-
nomics analysis have consequently been lacking.
The rapidly expanding field of epigenomics has the potential to
disentangle the influences of inheritance and environment on complex
diseases and greatly increase our understanding, as well as provide
biomarkers and therapeutics (Michels et al. 2013; Mill and Heijmans
2013). Therefore, it is desirable to study the epigenomics of Cynomolgus
macaque disease models. Although candidate gene approaches have
been reported (Rager et al. 2013), genome-wide approaches have been
hampered by the lack of suitable tools. Likewise, although high-coverage
MeDIP-seq approaches have been reported in the closely related rhesus
macaque (Bell et al. 2012; Provencal et al. 2012), this technique is
expensive, generally less quantitative, and has lower resolution.
The Infinium Human Methylation450 BeadChip Array (Infinium
450K) is a widely used tool in epigenetics that provides a robust and
cost-efficient way to measure genome-wide DNA methylation patterns.
It is a hybridization array designed to probe human genomic sequences
Copyright © 2014 Ong et al.
doi: 10.1534/g3.114.010967
Manuscript received March 10, 2014; accepted for publication May 3, 2014;
published Early Online May 8, 2014.
This is an open-access article distributed under the terms of the Creative
Commons Attribution Unported License (http://creativecommons.org/licenses/
by/3.0/), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Supporting information is available online at http://www.g3journal.org/lookup/
suppl/doi:10.1534/g3.114.010967/-/DC1
Gene Expression Omnibus Series (GSE) IDs: GSE52944 (Infinium 450K data),
GSE53596 (RRBS data).
1
Corresponding author: Singapore Institute for Clinical Sciences (SICS), Brenner
Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609.
E-mail: Joanna_Holbrook@sics.a-star.edu.sg
Volume 4 | July 2014 | 1227