“Gap hunting” to characterize clustered probe signals in Illumina methylation array data

Andrews, Shan V.; Ladd-Acosta, Christine; Feinberg, Andrew P.; Hansen, Kasper D.; Fallin, M. Daniele

doi:10.1186/s13072-016-0107-z

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“Gap hunting” to characterize clustered probe signals in Illumina methylation array data

Dec 07 2016
By Andrews, Shan V. ; Ladd-Acosta, Christine ; Feinberg, Andrew P. ; ...
http://dx.doi.org/10.1186/s13072-016-0107-z
Source: Epigenetics Chromatin. 9.

[PDF-2.20 MB]

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Details:

Alternative Title:

Epigenetics Chromatin
Personal Author:

Andrews, Shan V. ; Ladd-Acosta, Christine ; Feinberg, Andrew P. ; Hansen, Kasper D. ; Fallin, M. Daniele

Andrews, Shan V. ; Ladd-Acosta, Christine ; Feinberg, Andrew P. ; Hansen, Kasper D. ; Fallin, M. Daniele Less -
Description:

Background

The Illumina 450k array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple mapping locations. An additional set of potentially problematic probes are those with DNA methylation distributions characterized by two or more distinct clusters separated by gaps. Data-driven identification of such probes may offer additional insights for downstream analyses.

Results

We developed a procedure, termed “gap hunting,” to identify probes showing clustered distributions. Among 590 peripheral blood samples from the Study to Explore Early Development, we identified 11,007 “gap probes.” The vast majority (9199) are likely attributed to an underlying SNP(s) or other variant in the probe, although SNP-affected probes exist that do not produce a gap signals. Specific factors predict which SNPs lead to gap signals, including type of nucleotide change, probe type, DNA strand, and overall methylation state. These expected effects are demonstrated in paired genotype and 450k data on the same samples. Gap probes can also serve as a surrogate for the local genetic sequence on a haplotype scale and can be used to adjust for population stratification.

Conclusions

The characteristics of gap probes reflect potentially informative biology. QC pipelines may benefit from an efficient data-driven approach that “flags” gap probes, rather than filtering such probes, followed by careful interpretation of downstream association analyses. Our results should translate directly to the recently released Illumina EPIC array given the similar chemistry and content design.

Electronic supplementary material

The online version of this article (doi:10.1186/s13072-016-0107-z) contains supplementary material, which is available to authorized users.
Subjects:

[+]

450k Array Epigenome-wide Association Studies Gap Hunting Illumina HumanMethylation450 BeadChip Polymorphic CpG Research SNP
Source:

Epigenetics Chromatin. 9.
Pubmed ID:

27980682
Pubmed Central ID:

PMC5142147
Document Type:

Journal Article
Funding:

U10 DD000180/DD/NCBDD CDC HHS/United States ; U10 DD000181/DD/NCBDD CDC HHS/United States ; R01 ES017646/ES/NIEHS NIH HHS/United States ; U10 DD000184/DD/NCBDD CDC HHS/United States ; U01 DD000498/DD/NCBDD CDC HHS/United States ; ... More +

U10 DD000180/DD/NCBDD CDC HHS/United States ; U10 DD000181/DD/NCBDD CDC HHS/United States ; R01 ES017646/ES/NIEHS NIH HHS/United States ; U10 DD000184/DD/NCBDD CDC HHS/United States ; U01 DD000498/DD/NCBDD CDC HHS/United States ; U10 DD000182/DD/NCBDD CDC HHS/United States ; U10 DD000183/DD/NCBDD CDC HHS/United States Less -
Collection(s):

CDC Public Access
Main Document Checksum:

[+]

urn:sha256:56d4bdcb64742970192322e4426f1f7c896b7519789a6feba536a837a369846a
Download URL:

https://stacks.cdc.gov/view/cdc/44865/cdc_44865_DS1.pdf
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