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PXD039859-1

PXD039859 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNetwork-based elucidation of colon cancer drug resistance by phosphoproteomic time-series analysis
DescriptionAberrant signaling pathway activity is a hallmark of tumorigenesis and progression, which has guided targeted inhibitor design for over 30 years. Yet, adaptive resistance mechanisms, induced by rapid, context-specific signaling network rewiring, continue to challenge therapeutic efficacy. By leveraging progress in proteomic technologies and network-based methodologies over the past decade we developed VESPA, an algorithm designed to elucidate mechanisms of cell response and adaptation to drug perturbations, and used it to analyze 7-point phosphoproteomic time series from colorectal cancer cells treated with clinically-relevant inhibitors and control media. Interrogation of tumor-specific enzyme/substrate interactions accurately inferred kinase and phosphatase activity, based on their inferred substrate phosphorylation state, effectively accounting for signal cross-talk and sparse phosphoproteome coverage. The analysis elucidated time-dependent signaling pathway response to each drug perturbation and, more importantly, cell adaptive response and rewiring that was experimentally confirmed by CRISPRko assays, suggesting broad applicability to cancer and other diseases.
HostingRepositoryMassIVE
AnnounceDate2024-03-01
AnnouncementXMLSubmission_2024-03-01_02:27:09.906.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGeorge Rosenberger
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListPhospho
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-04 13:19:12ID requested
12024-03-01 02:27:10announced
Publication List
no publication
Keyword List
submitter keyword: Data-independent acquisiton, DIA, OpenSWATH, VESPA, Network inference, Signaling, Machine learning, VIPER
Contact List
Andrea Califano
contact affiliationColumbia University, NY, USA
contact emailac2248@cumc.columbia.edu
lab head
George Rosenberger
contact affiliationColumbia University
contact emailgr2578@cumc.columbia.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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