Transcriptomics,Genomics

Dataset Information

7

Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks


ABSTRACT: Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research. Genome-wide profiling of chromatin states and gene expression levels in 88 CLL samples from 55 individuals gave rise to 88 ATAC-seq profiles, 40 ChIPmentation profiles (10 samples, each with 3 different antibodies and matched immunoglobulin control), and 10 RNA-seq profiles. Raw sequence data has been deposited at the EBI's European Genome-phenome Archive (EGA) under the accession number EGAS00001001821 (controlled access to protect patient privacy).

ORGANISM(S): Homo sapiens  

SUBMITTER: Jonathan C Strefford   David Oscier  Zadie Davis  Matthias Farlik  Christian Schmidl  Christoph Bock  Andre F Rendeiro  Renata Walewska 

PROVIDER: E-GEOD-81274 | ArrayExpress | 2016-06-26

SECONDARY ACCESSION(S): GSE81274PRJNA321180

REPOSITORIES: GEO, ArrayExpress

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Publications

Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks.

Rendeiro André F AF   Schmidl Christian C   Strefford Jonathan C JC   Walewska Renata R   Davis Zadie Z   Farlik Matthias M   Oscier David D   Bock Christoph C  

Nature communications 20160627


Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients measured by the ATAC-seq assay. We also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting data set, we devised and applied a bioinformatic method that links  ...[more]

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