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Genome-Scale Exon Perturbation Screens Uncover Critical Exons for Cell Fitness [RNA-seq]

GSE244357 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/06/24 Platform GPL24676
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: 3 × mRNA-seq of Hek293 FLP-in cells with siNT, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5+TAF5-FL, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5+TAF5-DE8,Groups 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
Genome-scale exon perturbation screens uncover exons critical for cell fitnessMolecular cell · 2024
Summary (written by the submitters)
CRISPR-Cas technology has transformed functional genomics, yet understanding of how individual exons differentially shape cellular phenotypes remains limited. Here, we optimized and conducted massively parallel exon deletion and splice-site mutation screens in human cell lines to identify exons that regulate cellular fitness. Fitness-promoting exons are prevalent in essential and highly expressed genes and commonly overlap with protein domains and interaction interfaces.
Read the full summary ↓
Conversely, fitness-suppressing exons are enriched in nonessential genes, exhibiting lower inclusion levels, and overlap with intrinsically disordered regions and disease-associated mutations. In-depth mechanistic investigation of the screen-hit TAF5 alternative exon-8 revealed that its inclusion is required for assembly of the TFIID general transcription initiation complex, thereby regulating global gene expression output. Collectively, our orthogonal exon perturbation screens established a comprehensive repository of phenotypically important exons and uncovered regulatory mechanisms governing cellular fitness and gene expression.
Published in
Genome-scale exon perturbation screens uncover exons critical for cell fitness
Xiao MS, Damodaran AP, Kumari B et al. · Molecular cell 2024 · PMID 38917794 · doi:10.1016/j.molcel.2024.05.024
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 GSE244357_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 PRJNA1022470 and SRA study SRP463976. Searching any of these in the dataset finder brings you back here.

Study design
3 × mRNA-seq of Hek293 FLP-in cells with siNT, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5+TAF5-FL, vs 3 × mRNA-seq of Hek293 FLP-in cells with siTAF5+TAF5-DE8,

Supports a between-group comparison across 12 samples.

How we read this: 4 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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