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Synthetic Introns Identify GPATCH8 as Required for Mis-splicing by SF3B1 Mutations [RNA-Seq 2]

GSE262021 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/03/20 Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples: 6 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
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.
Paper
GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignanciesMolecular cell · 2024
Summary (written by the submitters)
Mutations in the RNA splicing factor SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing but therapeutic means to correct this mis-splicing do not exist. Here we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors required for aberrant mutant SF3B1 splicing activity.
Read the full summary ↓
This revealed the G-patch domain containing protein GPATCH8 as required for mutant SF3B1-induced splicing alterations and impaired hematopoiesis. GPATCH8 is involved in quality control of branchpoint selection, interacts with the RNA helicase DHX15, and functionally opposes SUGP1, a G-patch protein recently implicated in SF3B1 mutant diseases. Silencing of GPATCH8 corrected one-third of mutant SF3B1 splicing defects and was sufficient to improve hematopoiesis in SF3B1 mutant mouse and human cells. These data identify GPATCH8 as a novel splicing factor required for mis-splicing by mutant SF3B1 and the therapeutic impact of correcting aberrant splicing in SF3B1 mutant cancers.
Published in
GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies
Benbarche S, Pineda JMB, Galvis LB et al. · Molecular cell 2024 · PMID 38688280 · doi:10.1016/j.molcel.2024.04.006
This dataset
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.

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 GSE262021_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1090048 and SRA study SRP496696. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in duplicate
K700E,AAVS1-KO,non-differentiated, ×2 K700E,AAVS1-KO,erythroid-differentiated, ×2 K700E,GPATCH8-KO,non-differentiated, ×2 K700E,GPATCH8-KO,erythroid-differentiated, ×2 K700K,AAVS1-KO,non-differentiated, ×2 K700K,AAVS1-KO,erythroid-differentiated, ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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