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.