GEO series

Cryptic splicing mediates genetic and therapeutic perturbation of human gene expression levels [naRNA_LCLs]

GSE252005 Homo sapiens (human) RNA-seq (gene expression) 86 samples Submitted 2024/05/10 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 86 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: 86 samples: 86 × naRNA-seq of LCLs, NAGroups 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: Global impact of unproductive splicing on human gene expressionNature genetics · 2024

Summary (written by the submitters)

Alternative splicing (AS) in human genes is widely viewed as a mechanism for enhancing proteomic diversity. AS can also impact gene expression levels without increasing protein diversity by producing “unproductive” transcripts that are targeted for rapid degradation by nonsense-mediated decay (NMD). However, the relative importance of this regulatory mechanism remains underexplored.

Read the full summary ↓

To better understand the impact of AS-NMD relative to other regulatory mechanisms, we analyzed population-scale genomic data across eight molecular assays, covering various stages from transcription to cytoplasmic decay. We report threefold more unproductive splicing compared to prior estimates using steady-state RNA. This unproductive splicing compounds across multi-intronic genes, resulting in 15% of all transcript molecules from protein-coding genes being unproductive. Leveraging genetic variation across cell lines, we find that GWAS trait-associated loci explained by AS are as often associated with NMD-induced expression level differences as with differences in protein isoform usage. Employing the splice-switching drug risdiplam to manipulate AS at hundreds of genes, we find that ~3/4 of drug-induced isoforms are targeted by NMD, suggesting that most aberrant splicing influences expression levels. Our findings suggest much of the impact of AS is mediated by NMD-induced changes in gene expression rather than diversification of the proteome.

Published in

Global impact of unproductive splicing on human gene expression

Fair B, Buen Abad Najar CF, Zhao J et al. · Nature genetics 2024 · PMID 39223315 · doi:10.1038/s41588-024-01872-x

This dataset

Open GSE252005 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 GSE252005_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 PRJNA1021544 and SRA study SRP463418. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39223315) ↗

Study design

86 × naRNA-seq of LCLs, NA

Supports a between-group comparison across 86 samples.

How we read this: 1 replicated groups read from 86 sample titles; they account for 86 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

GSM7991468 naRNA-seq of LCLs, NA18486 naRNA-seq of LCLs, NA
GSM7991469 naRNA-seq of LCLs, NA18497 naRNA-seq of LCLs, NA
GSM7991470 naRNA-seq of LCLs, NA18498 naRNA-seq of LCLs, NA
GSM7991471 naRNA-seq of LCLs, NA18499 naRNA-seq of LCLs, NA
GSM7991472 naRNA-seq of LCLs, NA18502 naRNA-seq of LCLs, NA
GSM7991473 naRNA-seq of LCLs, NA18504 naRNA-seq of LCLs, NA
GSM7991474 naRNA-seq of LCLs, NA18505 naRNA-seq of LCLs, NA
GSM7991475 naRNA-seq of LCLs, NA18507 naRNA-seq of LCLs, NA
GSM7991476 naRNA-seq of LCLs, NA18508 naRNA-seq of LCLs, NA
GSM7991477 naRNA-seq of LCLs, NA18510 naRNA-seq of LCLs, NA
GSM7991478 naRNA-seq of LCLs, NA18511 naRNA-seq of LCLs, NA
GSM7991479 naRNA-seq of LCLs, NA18516 naRNA-seq of LCLs, NA
GSM7991480 naRNA-seq of LCLs, NA18519 naRNA-seq of LCLs, NA
GSM7991481 naRNA-seq of LCLs, NA18520 naRNA-seq of LCLs, NA
GSM7991482 naRNA-seq of LCLs, NA18522 naRNA-seq of LCLs, NA
GSM7991483 naRNA-seq of LCLs, NA18523 naRNA-seq of LCLs, NA
GSM7991484 naRNA-seq of LCLs, NA18852 naRNA-seq of LCLs, NA
GSM7991485 naRNA-seq of LCLs, NA18853 naRNA-seq of LCLs, NA
GSM7991486 naRNA-seq of LCLs, NA18858 naRNA-seq of LCLs, NA
GSM7991487 naRNA-seq of LCLs, NA18862 naRNA-seq of LCLs, NA
GSM7991488 naRNA-seq of LCLs, NA18864 naRNA-seq of LCLs, NA
GSM7991489 naRNA-seq of LCLs, NA18867 naRNA-seq of LCLs, NA
GSM7991490 naRNA-seq of LCLs, NA18868 naRNA-seq of LCLs, NA
GSM7991491 naRNA-seq of LCLs, NA18870 naRNA-seq of LCLs, NA
GSM7991492 naRNA-seq of LCLs, NA18876 naRNA-seq of LCLs, NA
GSM7991493 naRNA-seq of LCLs, NA18877 naRNA-seq of LCLs, NA
GSM7991494 naRNA-seq of LCLs, NA18879 naRNA-seq of LCLs, NA
GSM7991495 naRNA-seq of LCLs, NA18881 naRNA-seq of LCLs, NA
GSM7991496 naRNA-seq of LCLs, NA18909 naRNA-seq of LCLs, NA
GSM7991497 naRNA-seq of LCLs, NA18910 naRNA-seq of LCLs, NA
GSM7991498 naRNA-seq of LCLs, NA18913 naRNA-seq of LCLs, NA
GSM7991499 naRNA-seq of LCLs, NA18915 naRNA-seq of LCLs, NA
GSM7991500 naRNA-seq of LCLs, NA18917 naRNA-seq of LCLs, NA
GSM7991501 naRNA-seq of LCLs, NA18923 naRNA-seq of LCLs, NA
GSM7991502 naRNA-seq of LCLs, NA18924 naRNA-seq of LCLs, NA
GSM7991503 naRNA-seq of LCLs, NA18934 naRNA-seq of LCLs, NA
GSM7991504 naRNA-seq of LCLs, NA19092 naRNA-seq of LCLs, NA
GSM7991505 naRNA-seq of LCLs, NA19093 naRNA-seq of LCLs, NA
GSM7991506 naRNA-seq of LCLs, NA19095 naRNA-seq of LCLs, NA
GSM7991507 naRNA-seq of LCLs, NA19096 naRNA-seq of LCLs, NA

+ 46 more — browse all 86 samples with per-sample file links →

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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.