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Infinium monkeys: Infinium 450K array for the Cynomolgus macaque (Macaca fascicularis)
Mei-Lyn Ong1, Peck Yean Tan1, Julia L MacIsaac2
1Singapore Institute of Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore 117609.
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 hybridization 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 methylation 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. Approximately 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 representation 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 sequence 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.
Insights
The Human Infinium 450K array can effectively measure DNA methylation in Cynomolgus macaque tissues. This method offers a cost-efficient way to study epigenetics in this important disease model.
Area of Science:
- Epigenetics and Genomics
- Comparative Genomics
- Non-human Primate Models
Background:
- The Cynomolgus macaque is a crucial animal model in biomedical research.
- Limited molecular tools are available for studying macaque epigenetics.
- The human genome sequence is highly conserved with the macaque genome.
Purpose of the Study:
- To evaluate the feasibility of using the Human Infinium 450K BeadChip Array for genome-wide DNA methylation analysis in Cynomolgus macaques.
- To establish a reliable method for interrogating the methylome of macaque tissues.
- To assess the concordance between array-based methylation data and bisulfite sequencing.
Main Methods:
- Assayed DNA methylation in 11 macaque muscle biopsies using the Infinium 450K array.
- Mapped Infinium 450K probes to the Cynomolgus macaque genome using sequence identity.
- Compared Infinium 450K data with reduced representation bisulfite sequencing (RRBS) data.
Main Results:
- Approximately 61% of Human Infinium 450K probes reliably mapped to the macaque genome and contained a CpG site.
- Probe hybridization efficiency correlated with sequence identity between human probes and the macaque genome.
- High concordance was observed between Infinium 450K array and RRBS data, improvable with filtering.
Conclusions:
- The Infinium 450K array is a viable tool for measuring DNA methylation in Cynomolgus macaque tissues.
- Filtering based on probe sequence identity and mismatch location enhances data reliability.
- A pipeline for array validation in other species using BLAST is provided.
