PXD011551-1

PXD011551 is an original dataset announced via ProteomeXchange.

Title	Integrated Phosphoproteomics and Transcriptional Classifiers Reveal Hidden RAS Signaling Dynamics in Multiple Myeloma
Description	A major driver of multiple myeloma is thought to be aberrant signaling, yet no kinase inhibitors have proven successful in the clinic. Here, we employ an integrated, systems approach combining phosphoproteomic and transcriptome analysis to dissect cellular signaling in multiple myeloma to inform precision medicine strategies. Collectively, these predictive models identify vulnerable signaling signatures and highlight surprising differences in functional signaling patterns between NRAS and KRAS mutants invisible to the genomic landscape. Transcriptional analysis suggests that aberrant MAPK pathway activation is only present in a fraction of RAS-mutated vs. WT RAS patients. These high-MAPK patients, enriched for NRAS Q61 mutations, have inferior outcomes whereas RAS mutations overall carry no survival impact. We further develop an interactive software tool to relate pharmacologic and genetic kinase dependencies in myeloma. These results may lead to improved stratification of MM patients in clinical trials while also revealing unexplored modes of Ras biology.
HostingRepository	PRIDE
AnnounceDate	2019-03-06
AnnouncementXML	Submission_2019-03-06_00:41:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu-Hsiu Lin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-01 02:55:50	ID requested
⏵ 1	2019-03-06 00:41:04	announced
2	2019-03-06 00:47:10	announced	Updated project metadata.

Dataset with its publication pending

submitter keyword: myeloma, phosphoproteomics, proteomics, kinase, RAS, KRAS, NRAS, MAPK, machine learning, signaling

Arun Paul Wiita
contact affiliation	Department of Laboratory Medicine, Wiita Lab, University of California, San Francisco, USA
contact email	arun.wiita@ucsf.edu
lab head
Yu-Hsiu Lin
contact affiliation	University of California, San Francisco
contact email	lin.yu.hsiu@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011551
     1. Label: PRIDE project
     2. Name: Integrated Phosphoproteomics and Transcriptional Classifiers Reveal Hidden RAS Signaling Dynamics in Multiple Myeloma