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Don't brush off buccal data heterogeneity.

ABSTRACT: Buccal epithelial cells are among the most clinically accessible tissues and are increasingly being used to identify epigenetic disease patterns. However, substantial variation in buccal DNA methylation patterns indicates heterogeneity of cell types within and between samples, raising questions of data quality. We systematically estimated cell-type composition for a large collection of buccal and saliva samples from 11 published studies of DNA methylation. In these we identified numerous cases of buccal samples with questionable purity, which may be affected by sampling from individuals with neurodevelopmental disorders, and by the brushes used for sample collection. Further challenges are involved in comparisons with tissues such as saliva, in which buccal component varies widely. We propose a reference-based method of correcting for buccal purity that reduces unwanted variation while preserving cross-tissue differences. Our work demonstrates the wide variation of buccal quality in epigenetic studies and suggests a possible approach to overcome this issue.

SUBMITTER: Turinsky AL

PROVIDER: S-EPMC6557604 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Don't brush off buccal data heterogeneity.

Turinsky Andrei L AL Butcher Darci T DT Choufani Sanaa S Weksberg Rosanna R Brudno Michael M

Epigenetics 20190201 2

Buccal epithelial cells are among the most clinically accessible tissues and are increasingly being used to identify epigenetic disease patterns. However, substantial variation in buccal DNA methylation patterns indicates heterogeneity of cell types within and between samples, raising questions of data quality. We systematically estimated cell-type composition for a large collection of buccal and saliva samples from 11 published studies of DNA methylation. In these we identified numerous cases o ...[more]

PMID: 30821575

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Project description:We studied mixed poly(ethylene oxide) (PEO) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes. The question we attempted to answer was: when the chain grafting points are laterally mobile, how will this lateral mobility influence the structure and phase behavior of the mixed brush? Three different model mixed PEO/PDMAEMA brush systems were prepared: (1) a laterally mobile mixed brush by spreading onto the air-water interface a mixture of poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PnBA) and poly(2-(dimethylamino)ethyl methacrylate)-poly(n-butyl acrylate) (PDMAEMA-PnBA) diblock copolymers (the specific diblock copolymers used will be denoted as PEO113-PnBA100 and PDMAEMA118-PnBA100, where the subscripts refer to the number-average degrees of polymerization of the individual blocks), (2) a mobility-restricted (inseparable) version of the above mixed brush prepared using a PEO-PnBA-PDMAEMA triblock copolymer (denoted as PEO113-PnBA89-PDMAEMA120) having respective brush molecular weights matched with those of the diblock copolymers, and (3) a different laterally mobile mixed PEO and PDMAEMA brush prepared from a PEO113-PnBA100 and PDMAEMA200-PnBA103 diblock copolymer combination, which represents a further more height-mismatched mixed brush situation than described in (1). These three mixed brush systems were investigated by surface pressure-area isotherm and X-ray (XR) reflectivity measurements. These experimental data were analyzed within the theoretical framework of a continuum self-consistent field (SCF) polymer brush model. The combined experimental and theoretical results suggest that the mobile mixed brush derived using the PEO113-PnBA100 and PDMAEMA118-PnBA100 combination (i.e., mixed brush System #1) undergoes a lateral macroscopic phase separation at high chain grafting densities, whereas the more height-mismatched system (System #3) is only microscopically phase separated under comparable brush density conditions even though the lateral mobility of the grafted chains is unrestricted. The macroscopic phase separation observed in the laterally mobile mixed brush system is in contrast with the microphase separation behavior commonly observed in two-dimensional laterally mobile charged small molecule mixtures. Further study is needed to determine the detailed morphologies of the macro- and microphase-separated mixed PEO/PDMAEMA brushes.

Project description:BackgroundMultiple investigators have established the feasibility of using buccal brush samples to genotype single nucleotide polymorphisms (SNPs) with high-density genome-wide microarrays, but there is currently no consensus on the accuracy of copy number variants (CNVs) inferred from these data. Regardless of the source of DNA, it is more difficult to detect CNVs than to genotype SNPs using these microarrays, and it therefore remains an open question whether buccal brush samples provide enough high-quality DNA for this purpose.MethodsTo demonstrate the quality of CNV calls generated from DNA extracted from buccal samples, compared to calls generated from blood samples, we evaluated the concordance of calls from individuals who provided both sample types. The Illumina Human660W-Quad BeadChip was used to determine SNPs and CNVs of 39 Arkansas participants in the National Birth Defects Prevention Study (NBDPS), including 16 mother-infant dyads, who provided both whole blood and buccal brush DNA samples.ResultsWe observed a 99.9% concordance rate of SNP calls in the 39 blood-buccal pairs. From the same dataset, we performed a similar analysis of CNVs. Each of the 78 samples was independently segmented into regions of like copy number using the Optimal Segmentation algorithm of Golden Helix SNP & Variation Suite 7.Across 640,663 loci on 22 autosomal chromosomes, segment-mean log R ratios had an average correlation of 0.899 between blood-buccal pairs of samples from the same individual, while the average correlation between all possible blood-buccal pairs of samples from unrelated individuals was 0.318. An independent analysis using the QuantiSNP algorithm produced average correlations of 0.943 between blood-buccal pairs from the same individual versus 0.332 between samples from unrelated individuals.Segment-mean log R ratios had an average correlation of 0.539 between mother-offspring dyads of buccal samples, which was not statistically significantly different than the average correlation of 0.526 between mother-offspring dyads of blood samples (p=0.302).ConclusionsWe observed performance from the subject-collected mail-in buccal brush samples comparable to that of blood. These results show that such DNA samples can be used for genome-wide scans of both SNPs and CNVs, and that high rates of CNV concordance were achieved whether using a change-point-based algorithm or one based on a hidden Markov model (HMM).

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Don't brush off buccal data heterogeneity.

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Don't brush off buccal data heterogeneity.

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