PXD024312

PXD024312 is an original dataset announced via ProteomeXchange.

Title	A Proteomic Platform to Identify Off-Target Proteins Associated with Therapeutic Modalities that Induce Protein Degradation or Gene Silencing
Description	Novel modalities such as Proteolysis Targeting Chimera (PROTAC) and RNA interference (RNAi) have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate abundance of off-target proteins. The first part of the study involves selecting a panel of off-target proteins and a platform of cell lines using evidence from genetics and pharmacology. This process yielded 2,813 proteins, forming the basis of a panel that we refer to as the “selected off-target proteome” (SOTP). An iterative algorithm was then used to identify appropriate cell lines. Four human cell lines out of 932 were selected that, collectively, expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins of interest in the 4 selected cell lines. Among over 10,000 quantifiable proteins identified, 1,828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing rationale selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-16_16:43:15.650.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ye Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-22 22:46:34	ID requested
⏵ 1	2022-02-16 16:43:16	announced

Liu X, Zhang Y, Ward LD, Yan Q, Bohnuud T, Hernandez R, Lao S, Yuan J, Fan F, A proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing. Sci Rep, 11(1):15856(2021) [pubmed]

submitter keyword: Proteomic platform for off-target screening for PROTAC or RNAi

Fan Fan
contact affiliation	Amgen Inc.
contact email	ffan@amgen.com
lab head
Ye Zhang
contact affiliation	Amgen
contact email	yzhang250@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024312
     1. Label: PRIDE project
     2. Name: A Proteomic Platform to Identify Off-Target Proteins Associated with Therapeutic Modalities that Induce Protein Degradation or Gene Silencing