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Series GSE46644 Query DataSets for GSE46644
Status Public on Aug 09, 2013
Title Charting a dynamic DNA methylation landscape of the human genome
Organism Homo sapiens
Experiment type Third-party reanalysis
Methylation profiling by high throughput sequencing
Summary DNA methylation is a defining feature of mammalian cellular identity and is essential for normal development. Most cell types, except germ cells and pre-implantation embryos, display relatively stable DNA methylation patterns, with 70-80% of all CpGs being methylated. Despite recent advances we still have a too limited understanding of when, where and how many CpGs participate in genomic regulation. Here we report the in depth analysis of 42 whole genome bisulfite sequencing (WGBS) data sets across 30 diverse human cell and tissue types. We observe dynamic regulation for only 21.8% of autosomal CpGs within a normal developmental context, a majority of which are distal to transcription start sites. These dynamic CpGs co-localize with gene regulatory elements, particularly enhancers and transcription factor binding sites (TFBS), which allow identification of key lineage specific regulators. In addition, differentially methylated regions (DMRs) often harbor SNPs associated with cell type related diseases as determined by GWAS. The results also highlight the general inefficiency of WGBS as 70-80% of the sequencing reads across these data sets provided little or no relevant information regarding CpG methylation. To further demonstrate the utility of our DMR set, we use it to classify unknown samples and identify representative signature regions that recapitulate major DNA methylation dynamics. In summary, although in theory every CpG can change its methylation state, our results confirm that only a fraction does so as part of coordinated regulatory programs. Therefore our selected DMRs can serve as a starting point to help guide novel, more effective reduced representation approaches to capture the most informative fraction of CpGs as well as further pinpoint putative regulatory elements.
 
Overall design Analysis of 42 human WGBS libraries comprising 30 distinct primary cell lines, tissues, in vitro derived cell types and cell lines.

BiSeq raw sequencing reads were aligned using maq in bisulfite mode (Li et al. 2008) or bsmap 2.7 (Xi et al. 2009) against human genome version hg19/GRCh37, discarding duplicate reads. DNA methylation calling was performed based on an extended custom software pipeline published previously for RRBS (Gu et al., 2010). The bed files contain all seen CpGs within the given library. The number of methylated reads/number of total reads is listed in the score column.

This study includes a re-analysis of Samples from the NIH Roadmap Epigenomics Mapping Consortium (REMC; GSE16256, GSE17312), Hodges et al. 2011 (GSE31971), Molaro et al. 2011 (GSE30340), and Xi et al. 2013.

WARNING: This submission is incomplete pending further deposits of raw data files from Meissner via EDACC.
 
Contributor(s) Meissner A
Citation(s) 23925113
Submission date May 03, 2013
Last update date May 15, 2019
Contact name Michael Johannes Ziller
Organization name Max Planck Institute of Psychiatry
Department Translational Psychiatry
Lab Ziller lab
Street address Kraepelinstrasse 2-10
City Munich
ZIP/Postal code 80804
Country Germany
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM1204459 Frontal_cortex_normal_1
GSM1204460 Frontal_cortex_normal_2
GSM1204461 Frontal_cortex_AD_1
Relations
Reanalysis of GSM1112820
Reanalysis of GSM1112821
Reanalysis of GSM1112839
Reanalysis of GSM1112840
Reanalysis of GSM1112841
Reanalysis of GSM1112842
Reanalysis of GSM1112848
Reanalysis of GSM675542
Reanalysis of GSM752295
Reanalysis of GSM791827
Reanalysis of GSM791828
Reanalysis of GSM818003
Reanalysis of GSM864032
Reanalysis of GSM916049
Reanalysis of GSM916050
Reanalysis of GSM916051
Reanalysis of GSM916052
Reanalysis of GSM491351
BioProject PRJNA201480
SRA SRP028600

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE46644_RAW.tar 1.8 Gb (http)(custom) TAR (of BED)
GSE46644_SamplesOverview.txt.gz 1.2 Kb (ftp)(http) TXT
GSE46644_SupplementaryTable.txt.gz 173.4 Mb (ftp)(http) TXT
GSE46644_SupplementaryTable_readme.txt.gz 969 b (ftp)(http) TXT
GSE46644_bedFiles_set1.tar.gz 2.6 Gb (ftp)(http) TAR
GSE46644_bedFiles_set2.tar.gz 3.0 Gb (ftp)(http) TAR
GSE46644_bedFiles_set3.tar.gz 2.7 Gb (ftp)(http) TAR
Raw data not provided for this record
Processed data is available on Series record
Processed data provided as supplementary file
Raw data are available in SRA

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