PXD052594-1

PXD052594 is an original dataset announced via ProteomeXchange.

Title	Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis
Description	Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we used an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed two distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing ILD patients, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a non-invasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes. References: Hallal, Mahmoud, Sophie Braga-Lagache, Jovana Jankovic, Cedric Simillion, Rémy Bruggmann, Anne-Christine Uldry, Ramanjaneyulu Allam, Manfred Heller, and Nicolas Bonadies. 2021. “Inference of Kinase-Signaling Networks in Human Myeloid Cell Line Models by Phosphoproteomics Using Kinase Activity Enrichment Analysis (KAEA).” BMC Cancer 21 (1): 789.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_09:58:47.729.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfred Heller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-27 08:34:13	ID requested
⏵ 1	2024-10-17 09:58:48	announced

10.1172/jci.insight.181757;

Lauer D, Magnin CY, Kolly LR, Wang H, Brunner M, Chabria M, Cereghetti GM, Gabry, ś HS, Tanadini-Lang S, Uldry AC, Heller M, Verleden SE, Klein K, Sarbu AC, Funke-Chambour M, Ebner L, Distler O, Maurer B, Gote-Schniering J, Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis. JCI Insight, 9(15):(2024) [pubmed]

submitter keyword: interstitial lung disease,radiomics, proteomics, multiomics, imaging, lung fibrosis, nintedanib

Janine Gote-Schniering
contact affiliation	University of Bern, Department of BioMedical Research (DBMR), Lung Precision Medicine (LPM) Program
contact email	janine.gote-schniering@unibe.ch
lab head
Manfred Heller
contact affiliation	Proteomics and Mass Spectrometry Core Facility, Departement for Biomedical Research, University of Berne
contact email	pmscf.dbmr@unibe.ch
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/2024/10/PXD052594

PRIDE project URI

• PRIDE
  1. PXD052594
     1. Label: PRIDE project
     2. Name: Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis