학술논문

Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker
Document Type
article
Source
Clinical Epigenetics. 14(1)
Subject
Biological Sciences
Genetics
Clinical Research
Brain Disorders
Human Genome
Adult
Infant
Newborn
Humans
CpG Islands
DNA Methylation
Glucocorticoids
Oligonucleotide Array Sequence Analysis
Genetic Markers
Dexamethasone
DNA methylation
Whole blood
Cord blood
Glucocorticoid
Algorithmic biomarker
450K versus 850K
Clinical Sciences
Paediatrics and Reproductive Medicine
Language
Abstract
BackgroundIdentifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation. Here, we compare the NDMI 850 to one we built using data from the Illumina Methylation 450K (NDMI 450).ResultsThe NDMI 450 consisted of 22 loci, 15 of which were present on the NDMI 850. In adult whole blood samples, the linear composite scores from NDMI 450 and NDMI 850 were highly correlated and had equivalent predictive accuracy for detecting DEX exposure among adult glioma patients and non-glioma adult controls. However, the NDMI 450 scores of newborn cord blood were significantly lower than NDMI 850 in samples measured with both assays.ConclusionsWe developed an algorithm that reproduces the DNA methylation glucocorticoid response score using 450K data, increasing the accessibility for researchers to assess this biomarker in archived or publicly available datasets that use the 450K version of the Illumina BeadChip array. However, the NDMI850 and NDMI450 do not give similar results in cord blood, and due to data availability limitations, results from sample types of newborn cord blood should be interpreted with care.