Dataset Information

Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis

ABSTRACT: 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.

INSTRUMENT(S): Bruker Daltonics timsTOF series

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Manfred Heller

LAB HEAD: Janine Gote-Schniering

PROVIDER: PXD052594 | Pride | 2024-10-17

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20220420_Inno_M12_Vehicle_DDA_DL_i01_BA4_1_2567.d.zip	Other
	20220420_Inno_M12_Vehicle_DIA_DL_i02_BA1_1_2928.d.zip	Other
	20220420_Inno_M3_Vehicle_DDA_DL_i01_BA1_1_2555.d.zip	Other
	20220420_Inno_M3_Vehicle__DIA_DL_i02_BA1_1_2556.d.zip	Other
	20220420_Inno_M5_Nintedanib_DDA_DL_i01_BA2_1_2559.d.zip	Other

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Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis.

Lauer David D Magnin Cheryl Y CY Kolly Luca R LR Wang Huijuan H Brunner Matthias M Chabria Mamta M Cereghetti Grazia M GM Gabryś Hubert S HS Tanadini-Lang Stephanie S Uldry Anne-Christine AC Heller Manfred M Verleden Stijn E SE Klein Kerstin K Sarbu Adela-Cristina AC Funke-Chambour Manuela M Ebner Lukas L Distler Oliver O Maurer Britta B Gote-Schniering Janine J

JCI insight 20240716 15

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 performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to ...[more]

PMID: 39012714

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