PXD050561

PXD050561 is an original dataset announced via ProteomeXchange.

Title	A multiscale functional map of somatic mutations in cancer integrating protein structure and network topology
Description	A major goal of cancer biology is to understand the mechanisms underlying tumorigenesis driven by somatically acquired mutations. Two distinct types of computational methodologies have emerged: one focuses on analyzing clustering of mutations within protein sequences and 3D structures, while the other characterizes mutations by leveraging the topology of protein-protein interaction network. Their insights are largely non-overlapping, offering complementary strengths. Here, we established a unified, end-to-end 3D structurally-informed protein interaction network propagation framework, NetFlow3D, that systematically maps the multiscale mechanistic effects of somatic mutations in cancer. The establishment of NetFlow3D hinges upon the Human Protein Structurome, a comprehensive repository we compiled that incorporates the 3D structures of every single protein as well as the binding interfaces of all known protein interactions in humans. NetFlow3D leverages the Structurome to integrate information across atomic, residue, protein and network levels: It conducts 3D clustering of mutations across atomic and residue levels on protein structures to identify potential driver mutations. It then anisotropically propagates their impacts across the protein interaction network, with propagation guided by the specific 3D structural interfaces involved, to identify significantly interconnected network "modules", thereby uncovering key biological processes underlying disease etiology. Applied to 1,038,899 somatic protein-altering mutations in 9,946 TCGA tumors across 33 cancer types, NetFlow3D identified 12,378 significant 3D clusters throughout the Human Protein Structurome, of which ~54% would not have been found if using only experimentally-determined structures. It then identified 28 significantly interconnected modules that encompass ~8-fold more proteins than applying standard network analyses.
HostingRepository	MassIVE
AnnounceDate	2024-08-07
AnnouncementXML	Submission_2024-08-07_21:00:32.972.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yingying Zhang
SpeciesList	scientific name: Human 293T cells;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-12 15:26:59	ID requested
⏵ 1	2024-08-07 21:00:33	announced

no publication

submitter keyword: Cancer Genomics, 3D Protein Structure, Interactome, Protein-Protein Interaction Network, TMT, IP-MS

Haiyuan Yu
contact affiliation	Cornell University
contact email	haiyuan.yu@cornell.edu
lab head
Yingying Zhang
contact affiliation	Cornell University
contact email	yz2296@cornell.edu
dataset submitter

MassIVE dataset URI

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://massive.ucsd.edu/v07/MSV000094298/