Topological ranks reveal functional knowledge encoded in biological networks: a comparative analysis

Motivation: Biological networks topology yields important insights into biological function, occurrence of diseases and drug design. In the last few years, different types of topological measures have been introduced and applied to infer the biological relevance of network components/interactions, according to their position within the network structure. Although comparisons of such measures have been previously proposed, to what extent the topology per se may lead to the extraction of novel biological knowledge has never been critically examined nor formalized in the literature.Results: We present a comparative analysis of nine outstanding topological measures, based on compact views obtained from the rank they induce on a given input biological network. The goal is to understand their ability in correctly positioning nodes/edges in the rank, according to the functional knowledge implicitly encoded in biological networks. To this aim, both internal and external (gold standard) validation criteria are taken into account, and six networks involving three different organisms (yeast, worm and human) are included in the comparison. The results show that a distinct handful of best-performing measures can be identified for each of the considered organisms, independently from the reference gold standard.