Review of processing and analysis methods for DNA methylation array data

Wilhelm-Benartzi, Charlotte S.; Koestler, Devin C.; Karagas, Margaret R.; Flanagan, James M.; Christensen, Brock C.; Kelsey, Karl T.; Marsit, Carmen J.; Houseman, E. Andrés; Brown, Robert E.

doi:10.1038/bjc.2013.496

Cited by 172 publications

(134 citation statements)

References 64 publications

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“…The data were background corrected, normalized to internal controls and quality control was performed at ARTICLE RESEARCH the probe and sample level. A total of 572 probes failed in greater than 25% of the samples owing to their detection P values being greater than 0.05, and these were removed from the data 51 . COMBAT was used to remove batch effects 52 .…”

Section: Methodsmentioning

confidence: 99%

Whole–genome characterization of chemoresistant ovarian cancer

Patch¹,

Christie²,

Etemadmoghadam³

et al. 2015

Nature

1,259

1,311

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Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

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Section: Methodsmentioning

confidence: 99%

Whole–genome characterization of chemoresistant ovarian cancer

Patch¹,

Christie²,

Etemadmoghadam³

et al. 2015

Nature

1,259

1,311

View full text Add to dashboard Cite

show abstract

“…All analyses were adjusted for age, sex, and batch and chip effects. The two last variables correspond to microarray plate on which samples were processed and their position on the plate, respectively to account for experimental variability between position and plates 180 . Because DNA methylation levels measured in peripheral blood DNA reflect the average level of DNA methylation in different cell types including lymphocytes, monocytes, neutrophils, basophils and eosinophils, all analyses were also adjusted for cell type composition to avoid any contamination bias 181,182,183 .…”

Section: Resultsmentioning

confidence: 99%

SASH1, a new potential link between smoking and atherosclerosis

et al. 2015

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“…There is consensus that Infinium 450K β-values should be normalized (28, 29) and several methods have been proposed. We considered three normalization methods (minfi-Illumina, SWAN and DASEN) in addition to using raw (un-normalized) β-values.…”

Section: Resultsmentioning

confidence: 99%

Expanding Epigenomics to Archived FFPE Tissues: An Evaluation of DNA Repair Methodologies

Siegel

Berglund

Riggs

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from fresh frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) have emerged; however, a direct comparison of FFPE DNA repair methods prior to analysis on genome-wide methylation array to matched FF tissues has not been conducted. Methods We conducted a systematic performance comparison of two DNA repair methods (REPLI-g Ligase vs. Infinium HD Restore Kit) on FFPE-DNA compared to matched FF tissues on the Infinium 450K array. A threshold of discordant methylation between FF-FFPE pairs was set at Δβ>0.3. The correlations of β-values from FF-FFPE pairs were compared across methods and experimental conditions. Results The Illumina Restore kit outperformed the REPLI-g ligation method with respect to reproducibility of replicates(R2>0.970), highly correlated β-values between FF-FFPE(R2>0.888), and fewest discordant loci between FF-FFPE(≤0.61%). The performance of the Restore kit was validated in an independent set of 121 FFPE tissues. Conclusions The Restore kit outperformed RELPI-g ligation in restoring FFPE-derived DNA prior to analysis on the Infinium 450K methylation array. Our findings provide critical guidance that may significantly enhance the breadth of diseases that can be studied by methylomic profiling. Impact Epigenomic studies using FFPE tissues should now be considered among cancers that have not been fully characterized from an epigenomic standpoint. These findings promote novel epigenome-wide studies focused on cancer etiology, identification of novel biomarkers, and developing targeted therapies.

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Review of processing and analysis methods for DNA methylation array data

Cited by 172 publications

References 64 publications

Whole–genome characterization of chemoresistant ovarian cancer

Whole–genome characterization of chemoresistant ovarian cancer

SASH1, a new potential link between smoking and atherosclerosis

Expanding Epigenomics to Archived FFPE Tissues: An Evaluation of DNA Repair Methodologies

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