PXD066623-1

PXD066623 is an original dataset announced via ProteomeXchange.

Title	Exon inclusion signatures enable accurate estimation of splicing factor activity
Description	Splicing factors control exon inclusion in messenger RNA, shaping transcriptome and proteome diversity. Their catalytic activity is regulated by multiple layers, making single-omic measurements on their own fall short in identifying which splicing factors underlie a phenotype. Here, we propose that splicing factor activity can be estimated by interpreting changes in exon inclusion. To see if this is the case we benchmarked methods to construct splicing factor→exon networks and calculate splicing factor activity. Combining RNA-seq perturbation-based networks with VIPER (virtual inference of protein activity by enriched regulon analysis) accurately captures splicing factor activation modulated by different regulatory layers. This approach consolidates splicing factor regulation into a single score derived solely from exon inclusion signatures, allowing functional interpretation of heterogeneous conditions. As a proof of concept, we identify recurrent cancer splicing programs, revealing oncogenic- and tumor suppressor-like splicing factors missed by conventional methods. These programs correlate with patient survival and key cancer hallmarks: initiation, proliferation, and immune evasion. Altogether, we show splicing factor activity can be accurately estimated from exon inclusion changes, enabling comprehensive analyses of splicing regulation with minimal data requirements. In this dataset, we share our results from analyzing the BJ fibroblast-based model for carcinogenesis through proteomics and phosphoproteomics.
HostingRepository	PRIDE
AnnounceDate	2025-07-27
AnnouncementXML	Submission_2025-07-27_12:50:50.980.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miquel Anglada Girotto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-27 11:41:51	ID requested
⏵ 1	2025-07-27 12:50:59	announced

Anglada-Girotto M, Segura-Morales C, Moakley DF, Zhang C, Miravet-Verde S, Califano A, Serrano L, Exon inclusion signatures enable accurate estimation of splicing factor activity. bioRxiv, ():(2025) [pubmed]

10.1101/2024.06.21.600051;

submitter keyword: cancer

alternative splicing

splicing factor

protein activity

VIPER

carcinogenesis

Luis Serrano
contact affiliation	Centre for Genomic Regulation (CRG)
contact email	luis.serrano@crg.eu
lab head
Miquel Anglada Girotto
contact affiliation	Centre for Genomic Regulation (CRG)
contact email	miquel.anglada@crg.eu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/07/PXD066623

PRIDE project URI

• PRIDE
  1. PXD066623
     1. Label: PRIDE project
     2. Name: Exon inclusion signatures enable accurate estimation of splicing factor activity