4.8 Article

PCprophet: a framework for protein complex prediction and differential analysis using proteomic data

Journal

NATURE METHODS
Volume 18, Issue 5, Pages 520-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41592-021-01107-5

Keywords

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Funding

  1. Swiss National Science Foundation [3100A0-688 107679, 31003A_166435]
  2. European Research Council [ERC20140AdG 670821]
  3. National Health and Medicine Research Council (NHMRC) of Australia CJ Martin Early Career Research Fellowship [1143366]
  4. Innovative Medicines Initiative project ULTRA-DD (FP07/2007-2013) [115766]
  5. ETH strategic focus area 'Personalized Health and Related Technologies (PHRT)'
  6. EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN) [875510]
  7. NHMRC Principal Research Fellowship [1137739]
  8. Swiss National Science Foundation (SNF) [31003A_166435] Funding Source: Swiss National Science Foundation (SNF)

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The study introduces a toolkit called PCprophet that predicts protein complexes and characterizes their changes using SEC-SWATH-MS data. PCprophet demonstrates improved performance compared to other methods and introduces a Bayesian approach to analyze changes in protein-protein interactions.
Despite the availability of methods for analyzing protein complexes, systematic analysis of complexes under multiple conditions remains challenging. Approaches based on biochemical fractionation of intact, native complexes and correlation of protein profiles have shown promise. However, most approaches for interpreting cofractionation datasets to yield complex composition and rearrangements between samples depend considerably on protein-protein interaction inference. We introduce PCprophet, a toolkit built on size exclusion chromatography-sequential window acquisition of all theoretical mass spectrometry (SEC-SWATH-MS) data to predict protein complexes and characterize their changes across experimental conditions. We demonstrate improved performance of PCprophet over state-of-the-art approaches and introduce a Bayesian approach to analyze altered protein-protein interactions across conditions. We provide both command-line and graphical interfaces to support the application of PCprophet to any cofractionation MS dataset, independent of separation or quantitative liquid chromatography-MS workflow, for the detection and quantitative tracking of protein complexes and their physiological dynamics.

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