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Related Concept Videos

Peptide Identification Using Tandem Mass Spectrometry01:33

Peptide Identification Using Tandem Mass Spectrometry

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Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
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Simultaneous targeted and discovery-driven clinical proteotyping using hybrid-PRM/DIA.

Sandra Goetze1,2,3, Audrey van Drogen4,5,6, Jonas B Albinus4,5

  • 1Institute of Translational Medicine (ITM), Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland. sandra.goetze@hest.ethz.ch.

Clinical Proteomics
|April 2, 2024
PubMed
Summary

This study introduces hybrid parallel reaction monitoring/data-independent acquisition (PRM/DIA) for sensitive digital biobanking of rare clinical samples. This novel method enhances proteomic analysis, improving biomarker detection and supporting clinical decision-making.

Keywords:
Clinical phenotypingData-independent acquisition (DIA)DiagnosticsHybrid-DIAHybrid-PRM/DIAMelanomaMolecular tumor boardParallel reaction monitoring (PRM)ProteotypingTranslational proteomics

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Area of Science:

  • Proteomics
  • Biobanking
  • Clinical Research

Background:

  • Digital biobanks are crucial for research, but current methods like data-independent acquisition (DIA) have limited sensitivity.
  • Targeted approaches like parallel reaction monitoring (PRM) are often used to supplement DIA for specific markers.

Purpose of the Study:

  • To introduce and evaluate a novel hybrid parallel reaction monitoring/data-independent acquisition (hybrid-PRM/DIA) technology.
  • To enhance the comprehensive digitization of rare clinical samples at the proteotype level with improved sensitivity and reproducibility.

Main Methods:

  • Applied hybrid-PRM/DIA, combining multiplexed PRM (MSxPRM) with DIA acquisition.
  • Utilized heavy-labeled reference peptides as triggers for MSxPRM to monitor endogenous peptides.
  • Evaluated the technology on tumor-associated antigens and in biobanked melanoma samples.

Main Results:

  • Demonstrated improved reproducibility and sensitivity for detecting endogenous peptides, including those near the detection limit.
  • Confirmed that MSxPRM scans did not compromise overall DIA performance.
  • Successfully monitored 28 relevant biomarker candidates in melanoma samples, with consistent and quantitative results.

Conclusions:

  • Hybrid-PRM/DIA offers a sensitive and reproducible strategy for detecting protein markers relevant to molecular tumor boards.
  • This approach facilitates the discovery of new biomarker candidates alongside targeted analysis.