A data-driven approach to preprocessing Illumina 450K methylation array data
Ruth Pidsley,Chloe C. Y. Wong,Manuela Volta,Katie Lunnon,Jonathan Mill,Jonathan Mill,Leonard C. Schalkwyk +6 more
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TLDR
It is demonstrated that quantile normalization methods produce marked improvement, even in highly consistent data, by all three metrics, and that careful selection of preprocessing steps can minimize variance and thus improve statistical power, especially for the detection of the small absolute DNA methylation changes likely associated with complex disease phenotypes.Abstract:
As the most stable and experimentally accessible epigenetic mark, DNA methylation is of great interest to the research community. The landscape of DNA methylation across tissues, through development and in disease pathogenesis is not yet well characterized. Thus there is a need for rapid and cost effective methods for assessing genome-wide levels of DNA methylation. The Illumina Infinium HumanMethylation450 (450K) BeadChip is a very useful addition to the available methods for DNA methylation analysis but its complex design, incorporating two different assay methods, requires careful consideration. Accordingly, several normalization schemes have been published. We have taken advantage of known DNA methylation patterns associated with genomic imprinting and X-chromosome inactivation (XCI), in addition to the performance of SNP genotyping assays present on the array, to derive three independent metrics which we use to test alternative schemes of correction and normalization. These metrics also have potential utility as quality scores for datasets. The standard index of DNA methylation at any specific CpG site is β = M/(M + U + 100) where M and U are methylated and unmethylated signal intensities, respectively. Betas (βs) calculated from raw signal intensities (the default GenomeStudio behavior) perform well, but using 11 methylomic datasets we demonstrate that quantile normalization methods produce marked improvement, even in highly consistent data, by all three metrics. The commonly used procedure of normalizing betas is inferior to the separate normalization of M and U, and it is also advantageous to normalize Type I and Type II assays separately. More elaborate manipulation of quantiles proves to be counterproductive. Careful selection of preprocessing steps can minimize variance and thus improve statistical power, especially for the detection of the small absolute DNA methylation changes likely associated with complex disease phenotypes. For the convenience of the research community we have created a user-friendly R software package called wateRmelon, downloadable from bioConductor, compatible with the existing methylumi, minfi and IMA packages, that allows others to utilize the same normalization methods and data quality tests on 450K data.read more
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Journal ArticleDOI
Blood DNA methylation markers associated with type 2 diabetes, fasting glucose, and HbA1c levels: An epigenome-wide association study in 316 adult twin pairs.
Zhaonian Wang,Hexiang Peng,Wenjing Gao,Weihua Cao,Jun Lv,Canqing Yu,Tao Huang,Dianjianyi Sun,Biqi Wang,Chunxiao Liao,Yuanjie Pang,Zengchang Pang,Liming Cong,Hua Wang,Xianping Wu,Yu Liu,Liming Li +16 more
TL;DR: Wang et al. as discussed by the authors explored the associations between DNA methylation and type 2 diabetes, fasting plasma glucose, and HbA1c using Illumina Infinium BeadChips.
Journal ArticleDOI
Integrative DNA Methylation and Gene Expression Analysis in the Prefrontal Cortex of Mexicans who died by Suicide.
Ana Luisa Romero-Pimentel,Ana Luisa Romero-Pimentel,Daniel Almeida,Said Muñoz-Montero,Claudia Rangel,Roberto Cuauhtemoc Mendoza-Morales,Eli Elier González-Sáenz,Corina Nagy,Gary Chen,Zahia Aouabed,Jean-François Théroux,Gustavo Turecki,Gabriela Martinez-Levy,Consuelo Walss-Bass,Nancy Monroy-Jaramillo,Edith A. Fernández-Figueroa,Amalia Gómez-Cotero,Fernando García-Dolores,Mirna Edith Morales-Marín,Humberto Nicolini +19 more
TL;DR: In this paper, the authors examined DNA methylation profiles and concordant gene expression changes in the prefrontal cortex of Mexicans who died by suicide and found evidence of altered DNA methylations profiles at 4,430 genomic regions together with 622 genes characterized by differential expression in cases versus controls.
Posted ContentDOI
Association between breastfeeding and DNA methylation over the life course: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Fernando Pires Hartwig,Fernando Pires Hartwig,G Davey Smith,Andrew J Simpkin,Andrew J Simpkin,Cesar G. Victora,Caroline L Relton,Doretta Caramaschi +7 more
TL;DR: The findings indicate that DNA methylation in childhood and adolescence may be predicted by breastfeeding, but further studies with sufficiently large samples for replication are required to identify robust associations.
Posted ContentDOI
Neighborhood environment, social cohesion, and epigenetic aging
Chantel L. Martin,Cavin K. Ward-Caviness,Radhika Dhingra,Tarek M. Zikry,Sandro Galea,Derek E. Wildman,Karestan C. Koenen,Monica Uddin,Allison E. Aiello +8 more
TL;DR: It is suggested that living in adverse neighborhood conditions can speed up epigenetic aging, while positive neighborhood characteristics may buffer effects.
Journal ArticleDOI
Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity.
Inaki Schniewind,Wahyu Wijaya Hadiwikarta,J Grajek,Jan Poleszczuk,Susan Richter,Mirko Peitzsch,Johannes Müller,Daria Klusa,Elke Beyreuther,Steffen Löck,Armin Lühr,Susanne Frosch,Christer Groeben,Ulrich Sommer,Mechthild Krause,Anna Dubrovska,Cläre von Neubeck,Ina Kurth,Claudia Peitzsch +18 more
TL;DR: In this article , the authors analyzed CSC marker dynamics in prostate cancer, head and neck cancer, and glioblastoma cells upon proton beam irradiation and found that proton irradiation has a higher potential to target CSCs through induction of complex DNA damages, lower rates of cellular senescence, and minor alteration in histone methylation pattern compared with conventional photon irradiation.
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