GEO series

H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers [Nalm-6]

GSE94999 Homo sapiens (human) RNA-seq (gene expression) 9 samples Submitted 2017/12/20 Platform GPL11154

At a glance

RNA-seq (gene expression) · human · 9 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 9 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factors SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Although cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, clinical means to therapeutically target the spliceosome do not currently exist.

Read the full summary ↓

Here, we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and selectively kills spliceosome-mutant epithelial and hematologic malignancies. The effects of H3B-8800 are entirely selective for the Sf3b complex, as evidenced by the identification of drug-resistant cells bearing mutations in Sf3b components. Although H3B-8800 modulates RNA splicing mediated by WT or cancer-associated SF3B1 mutants, its preferential effects on spliceosome-mutant cells is due to preferred retention of short, GC-rich introns, which are enriched in genes encoding a substantial number of spliceosome components. These data demonstrate the therapeutic potential of splicing modulation in spliceosome-mutant cancers.

This dataset

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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE94999_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA375102 and SRA study SRP100079. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 29457796) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 9 more — browse all 9 samples with per-sample file links →

Datasets on a similar topic

GSE95011 H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers 21 samples shares h3b-8800, spliceosome, modulator, lethality, splicing, induces, mutant
GSE94528 H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome mutant cancers [K562] 12 samples shares h3b-8800, spliceosome, modulator, lethality, splicing, induces, mutant
GSE241672 Integrating Gene Expression and Splicing Dynamics Across Dose-Response Oxidative Modulators 400 samples shares modulator, splicing
GSE304951 The U1 snRNP protein U1C and Helix H of U1 snRNA are critical for small molecule splicing modulator function 57 samples shares modulator, splicing
GSE312843 RBM39 Modulates UPR Signaling Through Alternative Splicing of IRE1α/ERN1 [Spliceosome_Inhibition_RNA-Seq] 20 samples shares spliceosome, splicing
GSE312841 RBM39 Modulates UPR Signaling Through Alternative Splicing of IRE1α/ERN1 [Spliceosome_Knockdown_RNA-Seq] 16 samples shares spliceosome, splicing
GSE66182 Oncogenic MYC induces a dependency on the spliceosome in human cancer 11 samples shares spliceosome, induces
GSE236625 PP2A inhibition instructs spliceosome phosphorylation patterns to create splicing vulnerability in colon adenocarcinoma 8 samples shares spliceosome, splicing

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.