Figure 1. A variant-resolution genome-to-proteome map.

(A) Schematic of the mass spectrometry-based proteomics and genetic mapping approach. (B) Representative reproducibility across biological replicates of the vineyard (RM) isolate; Pearson’s r as indicated. (C) Volcano plot illustrating log₂ fold-change in protein abundance (abscissa) and Benjamini-Hochberg-corrected t test p value (ordinate) between the vineyard (RM) and clinical (YJM) parents. n = 36 – 39. (D) Estimated abundance of Mcr1 and Gap1 (polygenic) and Rnr4 and Erg11 (transgressing) in RM parent (blue), YJM parent (orange), F₆ progeny (grey), and SGRP wild strains (green). Boxes show median and upper and lower quartiles; whiskers show 1.5 times the interquartile range. (E) Mean broad-sense heritability of protein abundance (ordinate) as a function of estimated absolute protein abundance (abscissa) for all proteins measured in at least 80% of samples. (F) Normalized C.V. amongst the SGRP wild strains as compared to the mean C.V. in the parental isolates (ordinate) as a function of normalized C.V. amongst F₆ progeny (abscissa). Pearson’s r as indicated. p value by t statistic. (G) Genetic mapping of a cis-acting SNP controlling the abundance of Mcr1. (H) Schematic and predicted AlphaFold2 protein structure of a cis-acting missense variant in Mcr1. (I) CRISPR reconstruction and mass spectrometry to validate the effect of the Mcr1^Gly240Ser variant. n = 6; p value by two-sided t test. (J) Histogram of the fraction of total variance explained by the global (cis- and trans-acting) model in this study (blue) and in a highly powered eQTL mapping study in budding yeast (pink) ¹². (K) Rarefaction plot of unique trans-acting pQTL associations (blue) discovered, ordered by decreasing estimated protein abundance. Also shown in grey is the same statistic for downsampled real data using only 50% of the F₆ progeny. See also Figure S1.