Journal ArticleDOI
Recommendations for the design and analysis of epigenome-wide association studies
Karin B. Michels,Alexandra M. Binder,Sarah Dedeurwaerder,Charles B. Epstein,John M. Greally,Ivo Gut,E. Andres Houseman,Benedetta Izzi,Karl T. Kelsey,Alexander Meissner,Alexander Meissner,Aleksandar Milosavljevic,Kimberly D. Siegmund,Christoph Bock,Christoph Bock,Christoph Bock,Rafael A. Irizarry +16 more
TLDR
Concepts for conducting a stringent and powerful EWAS are reviewed, including the choice of analyzed tissue, sources of variability and systematic biases, analytical solutions to EWAS-specific problems are outlined and caveats in interpretation of data generated from samples with cellular heterogeneity are highlighted.Abstract:
Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting susceptibility to disease. Epigenome-wide screening methods cover an increasing number of CpG sites, but the complexity of the data poses a challenge to separating robust signals from noise. Appropriate study design, a detailed a priori analysis plan and validation of results are essential to minimize the danger of false positive results and contribute to a unified approach. Epigenome-wide mapping studies in homogenous cell populations will inform our understanding of normal variation in the methylome that is not associated with disease or aging. Here we review concepts for conducting a stringent and powerful EWAS, including the choice of analyzed tissue, sources of variability and systematic biases, outline analytical solutions to EWAS-specific problems and highlight caveats in interpretation of data generated from samples with cellular heterogeneity.read more
Citations
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Journal ArticleDOI
Comprehensive analysis of DNA methylation data with RnBeads
TL;DR: RnBeads is a software tool for large-scale analysis and interpretation of DNA methylation data, providing a user-friendly analysis workflow that yields detailed hypertext reports (http://rnbeads.mpi-inf.mpg).
Journal ArticleDOI
The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes
Ai Ling Teh,Hong Pan,Li Chen,Mei-Lyn Ong,Shaillay Kumar Dogra,Johnny Wong,Julia L. MacIsaac,Sarah M Mah,Lisa M. McEwen,Seang-Mei Saw,Keith M. Godfrey,Yap Seng Chong,Kenneth Kwek,Chee Keong Kwoh,Shu E Soh,Mary Ff F. Chong,Mary Ff F. Chong,Sheila J. Barton,Neerja Karnani,Clara Y. Cheong,Jan Paul Buschdorf,Walter Stünkel,Michael S. Kobor,Michael J. Meaney,Peter D. Gluckman,Joanna D. Holbrook +25 more
TL;DR: This study surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity.
Journal ArticleDOI
Quantitative comparison of DNA methylation assays for biomarker development and clinical applications
Christoph Bock,Florian Halbritter,Francisco J. Carmona,Sascha Tierling,Paul Datlinger,Yassen Assenov,María Berdasco,Anke K. Bergmann,Keith Booher,Florance Busato,Mihaela Campan,Christina Dahl,Christina M. Dahmcke,Dinh Diep,Agustín F. Fernández,Clarissa Gerhäuser,Andrea Haake,Katharina Heilmann,Thomas Holcomb,Dianna Hussmann,Mitsuteru Ito,Ruth Kläver,Martin Kreutz,Marta Kulis,Virginia Lopez,Shalima S. Nair,Dirk S. Paul,Nongluk Plongthongkum,Wenija Qu,Ana C. Queirós,Frank Reinicke,Guido Sauter,Thorsten Schlomm,Aaron L. Statham,Clare Stirzaker,Ruslan Strogantsev,Rocío G. Urdinguio,Kimberly Walter,Dieter Weichenhan,Daniel J. Weisenberger,Stephan Beck,Susan J. Clark,Manel Esteller,Anne C. Ferguson-Smith,Mario F. Fraga,Per Guldberg,Lise Lotte Hansen,Peter W. Laird,José I. Martín-Subero,Anders O. H. Nygren,Ralf Peist,Christoph Plass,David S. Shames,Reiner Siebert,Xueguang Sun,Jörg Tost,Jörn Walter,Kun Zhan +57 more
TL;DR: The results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use are described, with amplicon bisulfite sequencing and bisulfITE pyrosequencing showing the best all-round performance.
Book ChapterDOI
Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases
Yan V. Sun,Yi-Juan Hu +1 more
TL;DR: This work summarizes major omics approaches available in population research, and reviews integrative approaches and methodologies interrogating multiple omic layers, which enhance the gene discovery and functional analysis of human diseases.
References
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