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Series GSE100672 Query DataSets for GSE100672
Status Public on Jan 26, 2019
Title Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration. By applying our method to a cohort of matched patient samples collected before and during ibrutinib therapy, we identified characteristic ibrutinib-induced changes that provide a starting point for the rational design of ibrutinib combination therapies. Specifically, we observed and validated preferential sensitivity to proteasome, PLK1, and mTOR inhibitors during ibrutinib treatment. More generally, our study establishes a broadly applicable method for investigating treatment-specific vulnerabilities by integrating the complementary perspectives of epigenetic cell states and phenotypic drug responses in primary patient samples.
Overall design 38 ATAC-seq samples from primary peripheral blood mononucleated cells (PBMC) from chronic lymphocytic leukemia patient with high leukemic cell count were produced.
Contributor(s) Schmidl C, Vladimer GI, Rendeiro AF, Schnabl S, Pemovska T, Krausgruber T, Araghi M, Krall N, Snijder B, Hubman R, Ringler A, Demirtas D, Lopez de la Fuente O, Hilgarth M, Skrabs C, Porpaczy E, Gruber M, Hörmann G, Kubicek S, Staber PB, Shehata M, Jäger U, Superti-Furga G, Bock C
Citation(s) 30692684
Submission date Jun 29, 2017
Last update date Jul 25, 2021
Contact name Christoph Bock
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (38)
GSM2690984 ATAC-seq for patient CLL1 during Ibrutinib treatment
GSM2690985 ATAC-seq for patient CLL1 before Ibrutinib treatment
GSM2690986 ATAC-seq for patient CLL10 before Ibrutinib treatment
BioProject PRJNA392468
SRA SRP110771

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Supplementary file Size Download File type/resource
GSE100672_RAW.tar 6.2 Gb (http)(custom) TAR (of BIGWIG, NARROWPEAK)
GSE100672_cll-ibrutinib.coverage.csv.gz 5.5 Mb (ftp)(http) CSV
GSE100672_cll-ibrutinib.coverage.normalized.annotated.csv.gz 29.4 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data provided as supplementary file

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