A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Paola Picotti - , ETH Zurich (Autor:in)
  • Mathieu Clément-Ziza - , Technische Universität Dresden (Autor:in)
  • Henry Lam - , Hong Kong University of Science and Technology (Autor:in)
  • David S. Campbell - , Institute for Systems Biology (Autor:in)
  • Alexander Schmidt - , Universität Basel (Autor:in)
  • Eric W. Deutsch - , Institute for Systems Biology (Autor:in)
  • Hannes Röst - , ETH Zurich (Autor:in)
  • Zhi Sun - , Institute for Systems Biology (Autor:in)
  • Oliver Rinner - , ETH Zurich, Biognosys AG (Autor:in)
  • Lukas Reiter - , ETH Zurich, Biognosys AG (Autor:in)
  • Qin Shen - , ETH Zurich, CAS - Shanghai Institute of Nutrition and Health (Autor:in)
  • Jacob J. Michaelson - , Technische Universität Dresden (Autor:in)
  • Andreas Frei - , ETH Zurich (Autor:in)
  • Simon Alberti - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Ulrike Kusebauch - , Institute for Systems Biology (Autor:in)
  • Bernd Wollscheid - , ETH Zurich (Autor:in)
  • Robert L. Moritz - , Institute for Systems Biology (Autor:in)
  • Andreas Beyer - , Zelluläre Netzwerke und Systembiologie (FoG), Biotechnologisches Zentrum (BIOTEC) (Autor:in)
  • Ruedi Aebersold - , ETH Zurich, University of Zurich (Autor:in)

Abstract

Experience from different fields of life sciences suggests that accessible, complete reference maps of the components of the system under study are highly beneficial research tools. Examples of such maps include libraries of the spectroscopic properties of molecules, or databases of drug structures in analytical or forensic chemistry. Such maps, and methods to navigate them, constitute reliable assays to probe any sample for the presence and amount of molecules contained in the map. So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage. Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome. We generated two versions of this mass-spectrometric map, one supporting discovery-driven (shotgun) and the other supporting hypothesis-driven (targeted) proteomic measurements. Together, the two versions of the map constitute a complete set of proteomic assays to support most studies performed with contemporary proteomic technologies. To show the utility of the maps, we applied them to a protein quantitative trait locus (QTL) analysis, which requires precise measurement of the same set of peptides over a large number of samples. Protein measurements over 78 S. cerevisiae strains revealed a complex relationship between independent genetic loci, influencing the levels of related proteins. Our results suggest that selective pressure favours the acquisition of sets of polymorphisms that adapt protein levels but also maintain the stoichiometry of functionally related pathway members.

Details

OriginalspracheEnglisch
Seiten (von - bis)266-270
Seitenumfang5
FachzeitschriftNature
Jahrgang494
Ausgabenummer7436
PublikationsstatusVeröffentlicht - 14 Feb. 2013
Peer-Review-StatusJa

Externe IDs

PubMed 23334424
ORCID /0000-0003-4017-6505/work/161409864

Schlagworte

ASJC Scopus Sachgebiete