PXD082653

PXD082653 is an original dataset announced via ProteomeXchange.

Title	SPARCS enables scalable recovery of complex image-based phenotypes for genetic screening
Description	Forward genetic screening links genotype to phenotype by introducing random genetic perturbations and identifying phenotype-altering mutations. Although genome-scale screens are routine for simple phenotypes in cultured cells, extending them to complex image-based phenotypes remains challenging. Here, we present spatially resolved CRISPR screening (SPARCS), a microscopy-based platform for forward genetic screening on single-cell images. SPARCS physically isolates mutants in situ by automated laser microdissection, enabling image-based screening at unprecedented scale with multimodal hit phenotyping. We demonstrate SPARCS in genome-wide CRISPR knockout screens of autophagosome formation and activation of the immune sensor STING across 70 million cells. Via machine learning-based image analysis, SPARCS recovered most macroautophagy genes and identified GPHR as a pH-dependent regulator of STING. Mass spectrometry-based proteomics of isolated hit cells revealed endoplasmic reticulum (ER)/Golgi disruption and nominated additional STING regulators via in silico perturbation modeling. These results establish SPARCS as a scalable platform for genome-wide genetic screening of complex cellular phenotypes with a proteome-level readout.
HostingRepository	PRIDE
AnnounceDate	2026-10-06
AnnouncementXML	Submission_2026-10-06_08:25:55.998.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sophia Mädler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-15 17:34:44	ID requested
⏵ 1	2026-10-06 08:25:56	announced

10.1016/J.CELL.2026.09.021;

10.1016/j.cell.2026.09.021;

submitter keyword: STING,Cell Culture

Matthias Mann
contact affiliation	Max Planck Institute of Biochemistry, Dept. of Proteomics and Signal Transduction, Martinsried, Germany
contact email	mmann@biochem.mpg.de
lab head
Sophia Mädler
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
contact email	maedler@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/2026/10/PXD082653

PRIDE project URI

• PRIDE
  1. PXD082653
     1. Label: PRIDE project
     2. Name: SPARCS enables scalable recovery of complex image-based phenotypes for genetic screening