(A) Cluster analysis of the SPI data. The 23 screens are arranged horizontally and the 727 GFP strains clustered vertically. High z-scores (positive; >2) in yellow and low (negative; < -1) scores in blue. Three distinct clusters are highlighted (a, b, and c) and described in Figure 4—figure supplement 6. (B) Spearman’s Rank Correlation Coefficients for the different SPI screens shows similar compartments give similar SPIs, for example, Sec63 and Loa1 cluster together as do two kinetochore proteins Nuf2 and Dad2. (C) The notched box-and-whisker plot indicates the distributions of the retest log growth ratios and indicates that SPIs produced by a query protein and a target protein from different compartments produce stronger growth defects than those from the same compartments (***indicates a p-value = 1.8x10-5, Wilcoxon's rank-sum). The plot shows the median value (bar) and quartiles (box), the whiskers show the minimum of the range or 1.5 interquartile ranges, outlying data points are indicated as circles and the notches indicate the 95% confidence intervals of the medians. (D) The GFP proteins with SPIs have, on average, more protein-protein interactions than non-SPI query proteins, the notched box-and-whisker plot is in the same format as panel B (***indicates a p-value <.2x10-16, Wilcoxon’s rank-sum). The 727 SPI query proteins (red) are superimposed upon the yeast interactome with proteins with ≥10 interactions shown as larger squares. (E) The CLIK interaction density plot for Sec63 is shown (see Figure 4—figure supplement 5 for the other CLIK plots). The ~500 Sec63 associations that show the strongest growth restriction have a high interaction density (inset).