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Protein interactomes are epitomes of incomplete and noisy networks. Methods for assessing link-reliability using exclusively topology are valuable in network biology, and their investigation facilitates the general understanding of topological mechanisms and models to draw and correct complex network connectivity. Here, I revise and extend the local-community-paradigm (LCP). Initially detected in brain-network topological self-organization and afterward generalized to any complex network, the LCP is a theory to model local-topology-dependent link-growth in complex networks using network automata. Four novel LCP-models are compared versus baseline local-topology-models. It emerges that the reliability of an interaction between two proteins is higher: (i) if their common neighbours are isolated in a complex (local-community) that has low tendency to interact with other external proteins; (ii) if they have a low propensity to link with other proteins external to the local-community. These two rules are mathematically combined in C1*: a proposed mechanistic model that, in fact, outperforms the others. This theoretical study elucidates basic topological rules behind self-organization principia of protein interactomes and offers the conceptual basis to extend this theory to any class of complex networks. The link-reliability improvement, based on the mere topology, can impact many applied domains such as systems biology and network medicine.

Modelling Self-Organization in Complex Networks Via a Brain-Inspired Network Automata Theory Improves Link Reliability in Protein Interactomes