Integrative Epigenomic Analysis of 127 Consolidated Genomes

All genome-wide maps of histone modifications, DNA accessibility, DNA methylation and RNA expression are freely available online. Raw sequencing data deposited at the Short Read Archive or dbGAP is linked from http://www.ncbi.nlm.nih.gov/geo/roadmap/epigenomics/. All primary processed data (including mapped reads) for profiling experiments are contained within Release 9 of the Human Epigenome Atlas (http://genboree.org/EdaccData/Release-9/). Complete metadata associated with each dataset in this collection is archived at GEO and describes samples, assays, data processing details and quality metrics collected for each profiling experiment.
Release 9 of the compendium contains uniformly pre-processed and mapped data from multiple profiling experiments (technical and biological replicates from multiple individuals and/or datasets from multiple centers). In order to reduce redundancy, improve data quality and achieve uniformity required for our integrative analyses, experiments were subjected to additional processing to obtain comprehensive data for 111 consolidated epigenomes (See methods sections below for additional details). Numeric epigenome identifiers EIDs (e.g. E001) and mnemonics for epigenome names were assigned for each of the consolidated epigenomes. Table S1 (QCSummary sheet) summarizes the mapping of the individual Release 9 samples to the consolidated epigenome IDs. Key metadata such as age, sex, anatomy, epigenome class (see below), ethnicity and solid/liquid status were summarized for the consolidated epigenomes. Datasets corresponding to 16 cell-lines from the ENCODE project (with epigenome IDs ranging from E114-E129) were also used in the integrative analyses^{23 (link)}. All datasets from the 127 consolidated epigenomes were subjected to processing filters to ensure uniformity in terms of read length based mappability and sequencing depth as described below.
Each of the 127 epigenomes included consolidated ChIP-seq datasets for a core set of histone modifications - H3K4me1, H3K4me3, H3K27me3, H3K36me3, H3K9me3 as well as a corresponding whole-cell extract sequenced control. 98 epigenomes and 62 epigenomes had consolidated H3K27ac and H3K9ac histone ChIP-seq datasets respectively. A smaller subset of epigenomes had ChIP-seq datasets for additional histone marks, giving a total of 1319 consolidated datasets (Table S1, QCSummary sheet). 53 epigenomes had DNA accessibility (DNase-seq) datasets. 56 epigenomes had mRNA-seq gene expression data. For the 127 consolidated epigenomes, a total of 104 DNA methylation datasets across 95 epigenomes involved either bisulfite treatment (WGBS or RRBS assays) or a combination of MeDIP-seq and MRE-seq assays. In addition to the 1936 datasets analyzed here across 111 reference epigenomes, the NIH Roadmap Epigenomics Project has generated an additional 869 genome-wide datasets, linked from GEO, the Human Epigenome Atlas, and NCBI, and also publicly and freely available.

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Kundaje A., Meuleman W., Ernst J., Bilenky M., Yen A., Kheradpour P., Zhang Z., Heravi-Moussavi A., Liu Y., Amin V., Ziller M.J., Whitaker J.W., Schultz M.D., Sandstrom R.S., Eaton M.L., Wu Y.C., Wang J., Ward L.D., Sarkar A., Quon G., Pfenning A., Wang X., Claussnitzer M., Coarfa C., Harris R.A., Shoresh N., Epstein C.B., Gjoneska E., Leung D., Xie W., Hawkins R.D., Lister R., Hong C., Gascard P., Mungall A.J., Moore R., Chuah E., Tam A., Canfield T.K., Hansen R.S., Kaul R., Sabo P.J., Bansal M.S., Carles A., Dixon J.R., Farh K.H., Feizi S., Karlic R., Kim A.R., Kulkarni A., Li D., Lowdon R., Mercer T.R., Neph S.J., Onuchic V., Polak P., Rajagopal N., Ray P., Sallari R.C., Siebenthall K.T., Sinnott-Armstrong N., Stevens M., Thurman R.E., Wu J., Zhang B., Zhou X., Beaudet A.E., Boyer L.A., De Jager P., Farnham P.J., Fisher S.J., Haussler D., Jones S., Li W., Marra M., McManus M.T., Sunyaev S., Thomson J.A., Tlsty T.D., Tsai L.H., Wang W., Waterland R.A., Zhang M., Chadwick L.H., Bernstein B.E., Costello J.F., Ecker J.R., Hirst M., Meissner A., Milosavljevic A., Ren B., Stamatoyannopoulos J.A., Wang T, & Kellis M. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317-330.

Publication 2015

Assays Biological Bisulfite Cell extract Cell lines Chip seq Dna methylation Dnase Epigenome Ethnicity Gene expression Genome H3k4me3 Histone Histone marks Human Mrna Rna expression

Corresponding Organization :

Other organizations : Massachusetts Institute of Technology, Vassar College, Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Broad Institute, Baylor College of Medicine, University of California, San Diego, Salk Institute for Biological Studies, Howard Hughes Medical Institute, University of Washington, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, University of Washington Medical Center, University of British Columbia, University of Zagreb, The University of Texas at Dallas, Center for Systems Biology, Washington University in St. Louis, University of Queensland, Stony Brook University, University of Southern California, University of California, Santa Cruz, University of Wisconsin–Madison, Children's Nutrition Research Center at Baylor College of Medicine, National Institute of Environmental Health Sciences, Ludwig Cancer Research

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Variable analysis

independent variables

None explicitly mentioned

dependent variables

Genome-wide maps of histone modifications
DNA accessibility
DNA methylation
RNA expression

control variables

Whole-cell extract sequenced control for histone ChIP-seq datasets

controls

Positive controls: None mentioned
Negative controls: Whole-cell extract sequenced control for histone ChIP-seq datasets

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