Centrality and the shortest path approach on the human interactome

A network is one of the most convenient way to represent interactions between biological entities in systems biology. A network of molecular interactions is a graph in which the vertices are biological component and the edges correspond to the interactions between them. Many notions and approaches for network analysis came to systems biology from the theory of graphs - a field of mathematics that study graphs. We focused on the study of the shortest path approach in this work. We investigated whether this approach yields valid molecular paths. To perform this, the shortest paths in the human interactome (derived from HPRD and HIPPIE databases) were found between all relevant combinations of proteins taken from eight well-studied highly conserved signaling pathways from the KEGG database (NF-kappa B, MAPK, Jak-STAT, mTOR, ErbB, Wnt, TGF-beta and the signaling part of the apoptotic process). Canonical paths were systematically compared with the shortest counterparts and centrality of vertices and paths in subnetworks induced by the shortest paths were analyzed. We found that the sets of the shortest paths contain the canonical counterparts only for very short canonical paths (length 2-3 interactions). We also found that high centrality vertices tend to belong to canonical counterparts, to less extent this can also be said about high centrality paths.