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

Journal: Nature methods
PMID: 33859439

Abstract

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.

Authors

  • Andrea Fossati
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Chen Li
    School of Computer Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • Federico Uliana
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Fabian Wendt
    Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zürich, Zürich, Switzerland.
  • Fabian Frommelt
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Peter Sykacek
    Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU), 1190, Tulln an der Donau, Austria.
  • Moritz Heusel
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Mahmoud Hallal
    Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Isabell Bludau
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Tümay Capraz
    European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
  • Peng Xue
    National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Jiangning Song
    College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia College of Information Engineering, Northwest A&F University, Yangling 712100, China, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia, National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China, Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, VIC 3800, Australia.
  • Bernd Wollscheid
    Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zürich, Zürich, Switzerland.
  • Anthony W Purcell
    Department of Biochemistry and Molecular Biology and Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Matthias Gstaiger
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland. matthias.gstaiger@imsb.biol.ethz.ch.
  • Ruedi Aebersold
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland. aebersold@imsb.biol.ethz.ch.

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