Estimating dispensable content in the human interactome.

摘要: Protein-protein interaction (PPI) networks (interactome networks) have successfully advanced our knowledge of molecular function, disease and evolution. While much progress has been made in quantifying errors biases experimental PPI datasets, it remains unknown what fraction the error-free PPIs cell are completely dispensable, i.e., effectively neutral upon disruption. Here, we estimate dispensable content human interactome by calculating fractions disrupted non-neutral mutations. Starting with reference determined experiments, construct a structural building homology-based three-dimensional models for PPIs. Next, map common mutations from healthy individuals as well Mendelian disease-causing onto interactome, perform structure-based calculations how these perturb interactome. Using predicted experimentally-determined perturbation patterns mutations, that <~20% is dispensable.