Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures

Schwalbe, Ed, Hicks, Debbie, Rafiee, Gholamreza, Bashton, Matthew, Gohlke, Henning, Enshaei, Amir, Potluri, Sandeep, Matthiesen, Jessie, Mather, Michael, Taleongpong, Pim, Chaston, Ria, Silmon, A., Curtis, A., Lindsey, Janet, Crosier, Stephen, Smith, A. J., Goschzik, Tobias, Doz, Francois, Rutkowski, Stefan, Lannering, Birgitta, Pietsch, Torsten, Bailey, Simon, Williamson, Daniel and Clifford, Steven (2017) Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures. Scientific Reports, 7. p. 13421. ISSN 2045-2322

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Official URL: http://dx.doi.org/10.1038/s41598-017-13644-1

Abstract

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

Item Type: Article
Uncontrolled Keywords: Bioinformatics, Methylation analysis, PCR-based techniques
Subjects: B800 Medical Technology
C400 Genetics
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Ed Schwalbe
Date Deposited: 20 Oct 2017 08:18
Last Modified: 25 Oct 2017 12:36
URI: http://nrl.northumbria.ac.uk/id/eprint/32352

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