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In vivo CRISPR screens reveal SCAF1 and USP15 as novel drivers of pancreatic cancer

GSE220556 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2024/03/31 Platform GPL21493
At a glance

RNA-seq (gene expression) · mouse · 20 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
Mus musculus (mouse)
Samples
20 samples: 9 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
In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancerNature communications · 2024
Summary (written by the submitters)
Functionally characterizing the genetic alterations that drive pancreatic cancer progression is a prerequisite for precision pedicine. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to assess the transforming potential of 125 recurrently mutated ‘long-tail’ pancreatic cancer genes, which revealed USP15 and SCAF1 as novel and potent pancreatic ductal adenocarcinoma PDAC tumor suppressors, with USP15 functioning in a haplo-insufficient manner.
Read the full summary ↓
Mechanistically, we found that loss of USP15 leads to reduced inflammatory responses associated with TNFa, TGF-b and IL6 signaling and sensitizes pancreatic cancer cells to PARP inhibition and Gemcitabine. Similarly, genetic ablation of SCAF1 reduced inflammatory responses linked to TNFa, TGF-b and mTOR signaling and increased sensitivity to PARP inhibition. Furthermore, we identified that loss of SCAF1 resulted in the formation of a truncated inactive USP15 isoform at the expense of full length USP15, functionally coupling SCAF1 and USP15. Notably, USP15 and SCAF1 mutations or copy number losses are observed in 31% of PDAC patients. Together, our results demonstrate the utility of in vivo CRISPR screens to integrate human cancer genomics with mouse modeling for selective discovery of novel cancer driver genes such as USP15 and SCAF1 with potential prognostic and therapeutic implications.
Published in
In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer
Martinez S, Wu S, Geuenich M et al. · Nature communications 2024 · PMID 38902237 · doi:10.1038/s41467-024-49450-3
This dataset
Open GSE220556 in finder → Find more mouse RNA-seq datasets →
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 GSE220556_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 PRJNA910197 and SRA study SRP412050. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38902237) ↗
Study design
9 conditions, mostly in duplicate
PDAC KrasG12D cell line sgLUC DMSO biol ×2 PDAC KrasG12D cell line sgLUC Olaparib Biol ×2 PDAC KrasG12D cell line sgScaf1 Olaparib Biol… ×2 PDAC KrasG12D cell line sgScaf1 DMSO Biol rep… ×2 PDAC KrasG12D cell line sgScaf1 Olaparib Biol… ×2 PDAC KrasG12D cell line sgUsp15 DMSO Biol re… ×2 PDAC KrasG12D cell line sgUsp15 Olaparib Biol… ×2 PDAC KrasG12D cell line sgUsp15 DMSO Biol rep… ×2 +3 more

Supports a between-group comparison across 18 samples.

How we read this: 9 replicated groups read from 20 sample titles; they account for 18 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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