PXD024932

PXD024932 is an original dataset announced via ProteomeXchange.

Title	Quantification of Raloxifene Specific 471 Da Adducts in CYP3A4 and P450-Reductase
Description	Drugs are often metabolized to reactive intermediates that form protein adducts. Adducts can inhibit critical proteins, elicit immune responses, and cause life threatening adverse drug reactions. The masses of metabolites are frequently unknown, rendering traditional mass spectrometry-based proteomics approaches incapable of adduct identification: masses require defining before searching. “Open” search algorithms address this problem. Here, we present Magnum, an open search tool optimized for adduct identification; and Limelight, a web-based data processing package for analysis and visualization of data from all existing search algorithms, incorporating specific tools for sample comparisons and xenobiotic-adduct discovery. We demonstrate, using three drug/protein combinations, our new methods and software tools enable accurate identification of xenobiotic-protein adducts with no prior knowledge of adduct masses or protein targets. Magnum outperforms existing tools in xenobiotic-protein adduct discovery, while Limelight fulfills a major need in the rapidly developing field of open searching, which until now has had no comprehensive data visualization tools.
HostingRepository	PanoramaPublic
AnnounceDate	2022-02-21
AnnouncementXML	Submission_2022-02-21_17:44:39.608.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Alex Zelter
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116; scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-22 20:20:35	ID requested
⏵ 1	2022-02-21 17:44:40	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: Raloxifene, CYP3A4, P450-Reductase, Open Search, Adduct, Magnum, Limelight, Reactive Metabolite

Michael MacCoss
contact affiliation	University of Washington, Genome Sciences
contact email	maccoss@uw.edu
lab head
Alex Zelter
contact affiliation	University of Washington, Biochemistry
contact email	azelter@uw.edu
dataset submitter

Panorama Public dataset URI