An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray

Genome Biology
Lucas A SalasBrock C Christensen

Abstract

Genome-wide methylation arrays are powerful tools for assessing cell composition of complex mixtures. We compare three approaches to select reference libraries for deconvoluting neutrophil, monocyte, B-lymphocyte, natural killer, and CD4+ and CD8+ T-cell fractions based on blood-derived DNA methylation signatures assayed using the Illumina HumanMethylationEPIC array. The IDOL algorithm identifies a library of 450 CpGs, resulting in an average R2 = 99.2 across cell types when applied to EPIC methylation data collected on artificial mixtures constructed from the above cell types. Of the 450 CpGs, 69% are unique to EPIC. This library has the potential to reduce unintended technical differences across array platforms.

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Citations

Aug 4, 2018·Genome Research·Lucas A SalasKarl T Kelsey
Mar 3, 2019·International Journal of Molecular Sciences·Shilpa PavethynathNoriko Sato
Jan 18, 2020·JAMA Network Open·Jacob K KresovichJack A Taylor
Jan 17, 2020·Human Molecular Genetics·Lucas A SalasBrock C Christensen
Mar 15, 2020·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Sara DielsWim Van Hul
Apr 3, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Gregory T JonesSally P A McCormick
Nov 20, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Kumaraswamy Naidu ChitralaMichele K Evans
Jul 11, 2019·BMC Medical Genomics·Eric Chater-DiehlRosanna Weksberg
Jul 22, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Parvaneh EbrahimiKristina E Akesson
Mar 19, 2020·BMC Bioinformatics·Joshua J LevyBrock C Christensen
Aug 28, 2020·Frontiers in Immunology·Héléne Toinét CronjéMarlien Pieters
Jul 17, 2019·Nature Communications·Xiangyu LuoYingying Wei
Aug 2, 2019·Bioinformatics·Joshua J LevyBrock C Christensen
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Nov 20, 2020·Clinical Epigenetics·Curtis L PetersenBrock C Christensen
Jan 31, 2021·Environmental Research·Jaehyun ParkSungho Won
Apr 4, 2020·American Journal of Human Genetics·Sanaa ChoufaniRosanna Weksberg
Mar 9, 2021·Epigenomics·Héléne T CronjéMarlien Pieters
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Methods Mentioned

BETA
flow cytometry
FACS
Assay

Software Mentioned

EPIC IDOL
RGChannelSet R
FlowSorted EPIC
IDOL
missMethyl
Bioconductor
EPIC
EnMIX
minfi Bioconductor package
DMR IDOL

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