title: A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis.
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.
authors: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093, Switzerland. paola.picotti@bc.biol.ethz.ch
authors: Paola
authors: P
authors: Picotti
authors: Mathieu
authors: M
authors: Clément-Ziza
authors: Henry
authors: H
authors: Lam
authors: David S
authors: DS
authors: Campbell
authors: Alexander
authors: A
authors: Schmidt
authors: Eric W
authors: EW
authors: Deutsch
authors: Hannes
authors: H
authors: Röst
authors: Zhi
authors: Z
authors: Sun
authors: Oliver
authors: O
authors: Rinner
authors: Lukas
authors: L
authors: Reiter
authors: Qin
authors: Q
authors: Shen
authors: Jacob J
authors: JJ
authors: Michaelson
authors: Andreas
authors: A
authors: Frei
authors: Simon
authors: S
authors: Alberti
authors: Ulrike
authors: U
authors: Kusebauch
authors: Bernd
authors: B
authors: Wollscheid
authors: Robert L
authors: RL
authors: Moritz
authors: Andreas
authors: A
authors: Beyer
authors: Ruedi
authors: R
authors: Aebersold
mesh_terms: D013058:Mass Spectrometry; D019151:Peptide Library; D011110:Polymorphism, Genetic; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D040641:Quantitative Trait Loci / Q000235:genetics*; D012016:Reference Values; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis* / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D019151:Peptide Library; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins