From evidence to inference: Probing the evolution of protein interaction networks

The evolutionary mechanisms by which protein interaction networks grow and change are beginning to be appreciated as a major factor shaping their present‐day structures and properties. Starting with a consideration of the biases and errors inherent in our current views of these networks, we discuss the dangers of constructing evolutionary arguments from naïve analyses of network topology. We argue that progress in understanding the processes of network evolution is only possible when hypotheses are formulated as plausible evolutionary models and compared against the observed data within the framework of probabilistic modeling. The value of such models is expected to be greatly enhanced as they incorporate more of the details of the biophysical properties of interacting proteins, gene phylogeny, and measurement error and as more advanced methodologies emerge for model comparison and the inference of ancestral network states.