02106nas a2200121   4500008004300000245013400043210006900177260001900246520164000265100002101905700002201926856003601948       2010                        en_Ud  00aMonotonicity, frustration, and ordered response: an analysis of the energy landscape of perturbed large-scale biological networks0 aMonotonicity frustration and ordered response an analysis of the  bBioMed Central3 aBackground. \\nFor large-scale biological networks represented as signed graphs, the index of frustration measures how far a network is from a monotone system, i.e., how incoherently the system responds to perturbations.\\nResults. \\nIn this paper we find that the frustration is systematically lower in transcriptional networks (modeled at functional level) than in signaling and metabolic networks (modeled at stoichiometric level). A possible interpretation of this result is in terms of energetic cost of an interaction: an erroneous or contradictory transcriptional action costs much more than a signaling/metabolic error, and therefore must be avoided as much as possible. Averaging over all possible perturbations, however, we also find that unlike for transcriptional networks, in the signaling/metabolic networks the probability of finding the system in its least frustrated configuration tends to be high also in correspondence of a moderate energetic regime, meaning that, in spite of the higher frustration, these networks can achieve a globally ordered response to perturbations even for moderate values of the strength of the interactions. Furthermore, an analysis of the energy landscape shows that signaling and metabolic networks lack energetic barriers around their global optima, a property also favouring global order.\\nConclusion. \\nIn conclusion, transcriptional and signaling/metabolic networks appear to have systematic differences in both the index of frustration and the transition to global order. These differences are interpretable in terms of the different functions of the various classes of networks.1 aIacono, Giovanni1 aAltafini, Claudio  uhttp://hdl.handle.net/1963/4055