← BioTransfer GEO Dataset Finder
GEO series

Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumor

GSE262030 Homo sapiens (human) RNA-seq (gene expression) 51 samples Submitted 2024/03/21 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 51 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
51 samples: 17 conditions, mostly in triplicateGroups 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
Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumorsbioRxiv : the preprint server for biology · 2024
Summary (written by the submitters)
Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1. Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST).
Read the full summary ↓
There is only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST. The genetic basis of NF1 syndrome makes associated tumors ideal for using synthetic drug sensitivity approaches to uncover vulnerabilities. We developed a drug discovery pipeline to identify therapeutics for NF1-related tumors using isogeneic pairs of NF1 proficient and deficient immortalized human Schwann cells. We utilized these in a large-scale high throughput screen (HTS) for drugs that preferentially kill NF1 deficient cells, which identified 23 compounds capable of killing NF1 deficient Schwann cells with selectivity. Multiple hits from this screen clustered into classes defined by method of action. Four clinically interesting drugs from these classes were tested in vivo using both a genetically engineered mouse model of high-grade peripheral nerve sheath tumors and human MPNST xenografts. All trugs tested showed single agent efficacy in these models as well as significant synergy when used in combination with the MEK inhibitor selumetinib. This HTS platform has yielded novel therapeutically relevant compounds for the treatment of NF1-associated tumors and can serve as a tool to rapidly evaluate new compounds and combinations in the future.
Published in
Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors
Williams KB, Larsson AT, Keller BJ et al. · bioRxiv : the preprint server for biology 2024 · PMID 38585724 · doi:10.1101/2024.03.25.585959
This dataset
Open GSE262030 in finder → Find more human 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 GSE262030_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 PRJNA1090069 and SRA study SRP496707. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38585724) ↗
Study design
17 conditions, mostly in triplicate
S462TY, untreated, 0 hr, batch 1, biol ×3 S462TY, untreated, 2 hr, batch 1, biol ×3 S462TY, DMSO, 2 hr, batch 1, biol ×3 S462TY, Selumetinib, 2 hr, batch 1, biol ×3 S462TY, DMSO, 24 hr, batch 2, biol ×3 S462TY, Rigosertib, 2 hr, batch 1, biol ×3 S462TY, Digoxin, 2 hr, batch 1, biol ×3 S462TY, Selumetinib&Digoxin, 2 hr, batch 1, b… ×3 +9 more

Supports a between-group comparison across 51 samples.

How we read this: 17 replicated groups read from 51 sample titles; they account for 51 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

+ 11 more — browse all 51 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

Share this dataset

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.