Study overview

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, which we complemented by ChIPmentation and RNA-seq data for a representative subset of samples. Furthermore, we devised a bioinformatic method for linking these 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 regulatory 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 browser tracks

Data Visualization: Interactive browser tracks for the chromatin accessibility landscape of CLL All data are available for interactive browsing:

Data

Data Analysis: The CLL chromatin accessibility map and gene regulatory networks for download

Name Description and link
Raw sequence data Available through the European Genome-phenome Archive (EGA)
Processed data Available through the Gene Expression Omnibus (GEO) repository
Cohort-level map of chromatin-accessible regions in CLL Accessibility values (quantile normalized, log2) and cohort level statistics (217 MB)
Hypervariable regions within sample groups with different IGHV mutation status BED file with regions more variable in mCLL (19.3 Kb) BED file with regions more variable in uCLL (37.5 Kb)
Differentially expressed genes between CLL disease subtypes uCLL vs mCLL (25.5 Kb) uCLL vs iCLL (43.5 Kb) iCLL vs mCLL (10.8 Kb)
Chromatin accessibility regions associated with IGHV mutation status BED file with associated regions (37.9 Kb) Accessibility values (quantile normalized, log2) and cohort level statistics of IGHV regions (3.2 MB)
Gene regulatory networks CLL cohort-level network (infered from all samples) (6.9 MB) CD19+ DNase-seq network (from publicly available data) (10.3 MB) mCLL cohort-level network (infered from IGHV mutated samples) (7.9 MB) uCLL cohort-level network (infered from IGHV unmutated samples) (5.4 MB)

Download the complete set of analysis outputs.

Software

To foster reproducibility and facilitate reuse, the source code underlying the analysis is contained in a Git repository at Github.

Citation

If you use these data in your research, please cite:

André F. Rendeiro*, Christian Schmidl*, Jonathan C. Strefford*, Renata Walewska, Zadie Davis, Matthias Farlik, David Oscier, Christoph Bock
Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks.
Nat. Commun. 7:11938 doi: 10.1038/ncomms11938 (2016).

* These authors contributed equally to this work