  Network-based methods are playing an increasingly important role in drug
design. Our main question in this paper was whether the efficiency of drug
target proteins to spread perturbations in the human interactome is larger if
the binding drugs have side effects, as compared to those which have no
reported side effects. Our results showed that in general, drug targets were
better spreaders of perturbations than non-target proteins, and in particular,
targets of drugs with side effects were also better spreaders of perturbations
than targets of drugs having no reported side effects in human protein-protein
interaction networks. Colorectal cancer-related proteins were good spreaders
and had a high centrality, while type 2 diabetes-related proteins showed an
average spreading efficiency and had an average centrality in the human
interactome. Moreover, the interactome-distance between drug targets and
disease-related proteins was higher in diabetes than in colorectal cancer. Our
results may help a better understanding of the network position and dynamics of
drug targets and disease-related proteins, and may contribute to develop
additional, network-based tests to increase the potential safety of drug
candidates.
