Comparative analysis of Illumina Mouse Methylation BeadChip and reduced-representation bisulfite sequencing for routine DNA methylation analysis

Lochlan J Fennell; Gunter Hartel; Diane M McKeone; Catherine E Bond; Alexandra Kane; Barbara A Leggett; Ann-Marie Patch; Vicki L J Whitehall

doi:10.1016/j.crmeth.2022.100323

Comparative analysis of Illumina Mouse Methylation BeadChip and reduced-representation bisulfite sequencing for routine DNA methylation analysis

Cell Rep Methods. 2022 Nov 1;2(11):100323. doi: 10.1016/j.crmeth.2022.100323. eCollection 2022 Nov 21.

Authors

Lochlan J Fennell^{1

2

3}, Gunter Hartel⁴, Diane M McKeone¹, Catherine E Bond^{1

3}, Alexandra Kane^{1

3

5}, Barbara A Leggett^{1

3

6}, Ann-Marie Patch⁷, Vicki L J Whitehall^{1

3

5}

Affiliations

¹ Conjoint Gastroenterology Laboratory, Cell and Molecular Biology Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
² Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Science, Monash University, 19 Innovation Walk, Clayton, VIC, Australia.
³ Faculty of Medicine, University of Queensland, St. Lucia, QLD, Australia.
⁴ Statistics Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
⁵ Conjoint Internal Medical Laboratories, Pathology Queensland, Brisbane, QLD, Australia.
⁶ Department of Gastroenterology and Hepatology, Royal Brisbane and Womens' Hospital, Brisbane, QLD, Australia.
⁷ Clinical Genomics Laboratory, Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.

Abstract

Researching the murine epigenome in disease models has been hampered by the lack of appropriate and cost-effective DNA methylation arrays. Here we perform a comprehensive, comparative analysis between the Mouse Methylation BeadChip (MMB) and reduced-representation bisulfite sequencing (RRBS) in two murine models of colorectal carcinogenesis. We evaluate the coverage, variability, and ability to identify differential DNA methylation of RRBS and MMB. We show that MMB is an effective tool for profiling the murine methylome that performs comparably with RRBS, identifying similar differentially methylated pathways. Although choice of technology is experiment dependent and will be predicated on the underlying biology being probed, these analyses provide insights into the relative strengths and weaknesses of each approach.

Keywords: DNA methylation; bioinformatics; colorectal; epigenetics; epigenome; gastroenterology; genomics; methylome; microarray; murine models.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA Methylation* / genetics
Epigenome
Mice
Sequence Analysis, DNA
Sulfites*

Substances

hydrogen sulfite
Sulfites