Connectivity Homology Enables Inter-Species Network Models of Synthetic Lethality
A. We randomly selected 20 mutually exclusive groups of protein complexes that contained exactly five subunits; we mapped the corresponding gene pairs to SINaTRA scores, and plotted a heat map of the results.
Data are not clustered and only one randomly sampling was performed. We observed that within-complex gene pairs have significantly higher SINaTRA scores (p<0.0001, Fisher’s exact test). B. We compared the SINaTRA scores of gene pairs with products in the same vs. different complexes for complexes with of 5 protein subunits (top), ≤10 proteins (middle), and any number (bottom). Although proteins in the same complex are always enriched for higher SINaTRA score, as complex size increases, complex membership becomes less indicative of two genes being SL. C. We compared the fraction of gene pairs with products in the same vs. different complexes for three SINaTRA cutoffs (0.95, 0.80, 0.50) as well as for all gene pairs. A SINaTRA cutoff of 0.95 has approximately half of its pairs associated with the same complex; however, a decrease in the cutoff shifts this balance. This may indicate an increase in different mechanisms of SL in pairs with lower scores. “All Pairs” shows the expected proportion of in-complex pairs in our data.