PXD025019

PXD025019 is an original dataset announced via ProteomeXchange.

Title	Discovery and visualization of uncharacterized drug-protein adducts using mass spectrometry
Description	Drugs are often metabolized to reactive intermediates that form protein adducts. Adducts can inhibit protein activity, elicit immune responses, and cause life threatening adverse drug reactions. The masses of reactive metabolites are frequently unknown, rendering traditional mass spectrometry-based proteomics approaches incapable of adduct identification. Here, we present Magnum, an open-mass search algorithm optimized for adduct identification, and Limelight, a web-based data processing package for analysis and visualization of data from all existing algorithms. Limelight incorporates tools for sam-ple comparisons and xenobiotic-adduct discovery. We validate our tools with three drug/protein combinations and apply our label free workflow to identify novel xenobiotic-protein adducts in CYP3A4. Our new methods and software enable ac-curate identification of xenobiotic-protein adducts with no prior knowledge of adduct masses or protein targets. Magnum outperforms existing label free tools in xenobiotic-protein adduct discovery, while Limelight fulfills a major need in the rap-idly developing field of open-mass searching, which until now lacked comprehensive data visualization tools.
HostingRepository	PRIDE
AnnounceDate	2022-02-24
AnnouncementXML	Submission_2022-02-24_09:07:09.390.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Zelter
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-25 23:39:04	ID requested
⏵ 1	2022-02-24 09:07:10	announced

Riffle M, Hoopmann MR, Jaschob D, Zhong G, Moritz RL, MacCoss MJ, Davis TN, Isoherranen N, Zelter A, Discovery and Visualization of Uncharacterized Drug-Protein Adducts Using Mass Spectrometry. Anal Chem, 94(8):3501-3509(2022) [pubmed]

submitter keyword: Penicillin, Dicloxacillin, Flucloxacillin, Raloxifene, CYP3A4, HSA, Human Serum Albumin, Plasma, P450-Reductase, Open Search, xenobiotic, Adduct, Reactive Metabolite, MSFragger, MetaMorpheus, open-pFind, MODa, Comet-PTM, comet, Magnum, Limelight

Michael MacCoss
contact affiliation	Department of Genome Sciences, University of Washington, Seattle, WA, USA
contact email	maccoss@uw.edu
lab head
Alex Zelter
contact affiliation	Department of Biochemistry, University of Washington, Seattle
contact email	azelter@uw.edu
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/2022/02/PXD025019

PRIDE project URI

• PRIDE
  1. PXD025019
     1. Label: PRIDE project
     2. Name: Discovery and visualization of uncharacterized drug-protein adducts using mass spectrometry