Proteomics

Dataset Information

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Discovery and visualization of uncharacterized drug-protein adducts using mass spectrometry


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat) Homo Sapiens (human)

SUBMITTER: Alex Zelter  

LAB HEAD: Michael MacCoss

PROVIDER: PXD025019 | Pride | 2022-02-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
AZ686repA_highB_raw.zip Other
AZ686repA_highB_results.zip Other
AZ686repA_std_raw.zip Other
AZ686repA_std_results.zip Other
AZ686repB_highB_raw.zip Other
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Publications

Discovery and Visualization of Uncharacterized Drug-Protein Adducts Using Mass Spectrometry.

Riffle Michael M   Hoopmann Michael R MR   Jaschob Daniel D   Zhong Guo G   Moritz Robert L RL   MacCoss Michael J MJ   Davis Trisha N TN   Isoherranen Nina N   Zelter Alex A  

Analytical chemistry 20220220 8


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  ...[more]

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