PXD025316-1

PXD025316 is an original dataset announced via ProteomeXchange.

Title	DISCO-MS: Proteomics of spatially identified tissues in whole organs
Description	Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. Liquid chromatography coupled to mass spectrometry (LC-MS) is emerging as a key technology for the unbiased characterization of proteins, the drivers of cellular function. Furthermore, recent advances in imaging, transcriptomics and proteomics allowed the analysis of spatially resolved RNA- and protein-profiles from thin tissue sections. However, so far, no method has allowed the unbiased mass spectrometry (MS)-based proteomics analysis of target tissues identified by unbiased imaging of whole organs in 3D. Here, we present DISCO-MS, a technology combining solvent-based tissue clearing, whole-organ imaging by light-sheet microscopy, automated image analysis powered by deep learning, and ultra-high sensitivity mass spectrometry. DISCO-MS yields qualitative and quantitative proteomics data indistinguishable from uncleared samples in both rodent and human tissue. DISCO-MS of the proteomes of axonal tracts with activated microglia after brain injury revealed known and novel biomarkers. We characterized individual initial amyloid beta plaques in the brains of a young familial Alzheimer's disease mouse model, determined the core proteome of these aggregates and highlighted compositional heterogeneity. DISCO-MS enables the image-guided identification of rare target tissues in intact biological systems followed by MS-based proteome analysis, providing new diagnostic and therapeutic opportunities for complex diseases including neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2025-12-05
AnnouncementXML	Submission_2025-12-04_21:25:45.506.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	time-of-flight; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 07:49:31	ID requested
⏵ 1	2025-12-04 21:25:46	announced

Bhatia HS, Brunner AD, Ö, zt, ü, rk F, Kapoor S, Rong Z, Mai H, Thielert M, Ali M, Al-Maskari R, Paetzold JC, Kofler F, Todorov MI, Molbay M, Kolabas ZI, Negwer M, Hoeher L, Steinke H, Dima A, Gupta B, Kaltenecker D, Caliskan Ö S, Brandt D, Krahmer N, M, ü, ller S, Lichtenthaler SF, Hellal F, Bechmann I, Menze B, Theis F, Mann M, Ert, ü, rk A, Spatial proteomics in three-dimensional intact specimens. Cell, 185(26):5040-5058.e19(2022) [pubmed]

10.1016/j.cell.2022.11.021;

submitter keyword: Ultra-high sensitivity proteomics

Proteomics

Tissue-clearing

Solvent-clearing

Familial Alzheimer’s disease

mild traumatic brain injury

Imaging

Spatial proteomics

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2025/11/PXD025316

PRIDE project URI

• PRIDE
  1. PXD025316
     1. Label: PRIDE project
     2. Name: DISCO-MS: Proteomics of spatially identified tissues in whole organs