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Deciphering the cis-regulatory code of alternative splicing in human cell lines

GSE307247 Homo sapiens Expression profiling by high throughput sequencing; Other 11 samples Submitted 2025/09/08 Platform GPL15520Platform GPL18573
Summary
Alternative splicing (AS) is a key mechanism of gene expression diversity, and dysregulation of AS is implicated in many human diseases. Identifying variants that disrupt splicing and characterizing their impact on isoform abundance across different cell types remains challenging. Here, we perform massively parallel reporter assays (MPRAs) to measure splicing phenotypes of over 87,000 sequence variants in five cell lines of different tissue origin. The MPRA encompasses 2,096 short human exons from 1,733 genes and tens of thousands of single and double variants. Our measurements identify variants that strongly modulate splicing but are currently classified as variants of unknown significance or have not yet been described. We systematically identify putative RNA-binding protein (RBP) binding motifs and quantify effect sizes associated with the disruption of these motifs, suggesting possible mechanisms for variant impact. A comparison across cell lines enables the identification of variants that differentially modulate splicing.
Published in
Massively parallel assay of human splice variants reveals cis-regulatory drivers of disease-associated and cell type-specific splicing regulation
Koplik SE, Yu AM, Shelby MR et al. · bioRxiv : the preprint server for biology 2025 · PMID 41280078 · doi:10.1101/2025.10.12.681955
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Direct links to NCBI, no account and no request form: the whole study as GSE307247_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 11 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1314833 and SRA study SRP617140. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly in duplicate
HEK293 MPRA ×2 HeLa MPRA ×2 HMC3 MPRA ×2 K562 MPRA ×2 MCF7 MPRA ×2 ESL DNA-seq ×1

Supports a between-group comparison across 10 samples.

5 replicated groups read from 11 sample titles; they account for 10 of them. Check it against the sample list below before relying on it.

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