Figure 5. Impact of potentially deleterious variants on the interactome of real and simulated individuals.

1. A–C Comparison of the interactome damage between real and random individuals after removing the nodes corresponding to proteins containing deleterious variants in both alleles (homozygote). Two different scenarios are simulated: Simulated populations with uniform probability, where proteins are randomly removed, and Simulated populations with observed frequencies, where proteins are removed with a probability proportional to the frequency of variation in the 1,000 genomes population (see Results). The comparison was performed using all the 1,000 genomes project populations (green box), the newly sequenced Spanish population MPG1 (blue box) and the germinal variants of the CLL patients (yellow box) and contrasting their distributions with the corresponding random distribution (grey boxes). The effects on the global network topology were defined by (A) the number of connections in the remaining interactome, (B) the average length of the shortest paths and (C) the total number of isolated components. P-values are provided for the comparisons of both simulation scenarios with real values.
2. D,E Visual illustration of the network components lost after removing nodes corresponding to damaged proteins in (D) a real individual from 1,000 genomes (HG01083 of the PUR population) and (E) a simulated individual with the same number of damaged proteins (i.e. nodes removed).