Training a model for estimating leukocyte composition using whole-blood DNA methylation and cell counts as reference
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Accepted version
Accepted version
Author(s)
Type
Journal Article
Abstract
Aim: Whole-blood DNA methylation depends on the underlying leukocyte composition and confounding hereby is a major concern in epigenome-wide association studies. Cell counts are often missing or may not be feasible. Computational approaches estimate leukocyte composition from DNA methylation based on reference datasets of purified leukocytes. We explored the possibility to train such a model on whole-blood DNA methylation and cell counts without the need for purification. Materials & methods: Using whole-blood DNA methylation and corresponding five-part cell counts from 2445 participants from the London Life Sciences Prospective Population Study, a model was trained on a subset of 175 subjects and evaluated on the remaining. Results: Correlations between cell counts and estimated cell proportions were high (neutrophils 0.85, eosinophils 0.88, basophils 0.02, lymphocytes 0.84, monocytes 0.55) and estimated proportions explained more variance in whole-blood DNA methylation levels than counts. Conclusion: Our model provided precise estimates for the common cell types.
Date Issued
2016-11-25
Date Acceptance
2016-10-18
Citation
Epigenomics, 2016, 9 (1), pp.13-20
ISSN
1750-192X
Publisher
Future Medicine
Start Page
13
End Page
20
Journal / Book Title
Epigenomics
Volume
9
Issue
1
Copyright Statement
© 2017 Future Medicine Ltd. Published in Epigenomics, January 2017 ,Vol. 9, No. 1, Pages 13-20 , DOI 10.2217/epi-2016-0091, available at https://dx.doi.org/10.2217/epi-2016-0091
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000392218200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
DNA methylation
estimation of cell proportions
Infinium 450K
KAROLA
leukocyte composition
LOLIPOP
white-blood cell distribution
EPIGENOME-WIDE ASSOCIATION
HEMATOLOGY ANALYZER
HETEROGENEITY
PERFORMANCE
SMOKING
BIRTH
Publication Status
Published