ChAMP: 450k Chip Analysis Methylation Pipeline

Morris, Tiffany; Butcher, Lee M.; Feber, Andrew; Teschendorff, Andrew E.; Chakravarthy, Ankur; Wojdacz, Tomasz K.; Beck, Stephan

doi:10.1093/bioinformatics/btt684

Cited by 808 publications

(675 citation statements)

References 20 publications

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“…The present study is the first to explore whole-genome DNA methylation status in HB. In the present study, Infinium HumanMethylation450 BeadChip, a new platform for high-throughput DNA methylation analysis, was used (25). The cluster analysis revealed markedly less methylation in HB tissues than in normal liver tissues in the three sets of paired tissues analyzed.…”

Section: B Amentioning

confidence: 92%

Genome-wide analysis of DNA methylation in hepatoblastoma tissues

et al. 2016

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Abstract. DNA methylation has a crucial role in cancer biology. In the present study, a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues was performed to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, AFP methylation levels were also detected using pyrosequencing. Normal and HB liver tissue samples (frozen tissue) were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation450 BeadChip, and the results were confirmed with reverse transcription-quantitative polymerase chain reaction. The Infinium HumanMethylation450 BeadChip demonstrated distinctively less methylation in HB tissues than in non-tumor tissues. In addition, methylation enrichment was observed in positions near the transcription start site of AFP, which exhibited lower methylation levels in HB tissues than in non-tumor liver tissues. Lastly, a significant negative correlation was observed between AFP messenger RNA expression and DNA methylation percentage, using linear Pearson's R correlation coefficients. The present results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of AFP in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology.

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Section: B Amentioning

confidence: 92%

Genome-wide analysis of DNA methylation in hepatoblastoma tissues

et al. 2016

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“…β values and M values were extracted from the remaining probes. Prediction of batch effects was carried out by singular value decomposition (SVD) using the champ bioconductor package (Morris et al ., 2014). Identification of differentially methylated CpG probes between sample groups was performed using a linear model fit of the M values with subsequent empirical Bayes reduction in standard errors from the estimated methylation differences, as described in the limma r package (Ritchie et al ., 2015).…”

Section: Methodsmentioning

confidence: 99%

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

et al. 2016

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SummaryEpigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age‐related changes in DNA methylation at the genome scale have been termed ‘epigenetic drift’, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age‐related epigenetic changes because of its substantial cell‐type homogeneity and its well‐known age‐related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array‐based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age‐related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age‐related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome.

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“…Quality control of bisulfite conversion was performed by quantitative PCR to confirm >98% conversion. Data analysis was performed using the ChAMP pipeline (13). Samples where !5% of probes failed detection P value < 0.01 filtering were excluded from further analysis.…”

Section: Dna Methylation Analysis: Illumina Humanmethylation450mentioning

confidence: 99%

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor

Karpathakis

Dibra

Pipinikas

et al. 2016

Clinical Cancer Research

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Purpose: Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type. Experimental Design: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43). Results: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%). Conclusions: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival. Clin Cancer Res; 22(1); 250–8. ©2015 AACR.

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ChAMP: 450k Chip Analysis Methylation Pipeline

Abstract: ChAMP is implemented as a Bioconductor package in R. The package and the vignette can be downloaded at bioconductor.org

Cited by 808 publications

References 20 publications

Genome-wide analysis of DNA methylation in hepatoblastoma tissues

Genome-wide analysis of DNA methylation in hepatoblastoma tissues

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor

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