Journal
BIOINFORMATICS
Volume 34, Issue 23, Pages 3983-3989Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/bty476
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Funding
- UK Medical Research Council
- Wellcome [102215/2/13/2]
- University of Bristol
- UK Economic and Social Research Council [ES/N000498/1]
- UK Medical Research Council [MC_UU_12013/1, MC_UU_12013/2]
- Danish National Research Foundation
- Danish Regional Committees
- Pharmacy Foundation
- Egmont Foundation
- March of Dimes Birth Defects Foundation
- Health Foundation
- Novo Nordisk Foundation
- Lundbeck Foundation
- Medical Research Council Integrative Epidemiology Unit - UK Medical Research Council
- Health Foundation [MC_UU_12013/1-9]
- BBSRC [BB/I025751/1] Funding Source: UKRI
- ESRC [ES/N000498/1] Funding Source: UKRI
- MRC [MC_UU_00011/1, MC_UU_12013/2, MC_UU_12013/1] Funding Source: UKRI
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Motivation: DNA methylation datasets are growing ever larger both in sample size and genome coverage. Novel computational solutions are required to efficiently handle these data. Results: We have developed meffil, an R package designed for efficient quality control, normalization and epigenome-wide association studies of large samples of Illumina Methylation BeadChip microarrays. A complete re-implementation of functional normalization minimizes computational memory without increasing running time. Incorporating fixed and random effects within functional normalization, and automated estimation of functional normalization parameters reduces technical variation in DNA methylation levels, thus reducing false positive rates and improving power. Support for normalization of datasets distributed across physically different locations without needing to share biologically-based individual-level data means that meffil can be used to reduce heterogeneity in meta-analyses of epigenome-wide association studies.
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