Drug-therapy networks and the predictions of novel drug targets

Recently, a number of drug-therapy, disease, drug, and drug-target networks have been introduced. Here we suggest novel methods for network-based prediction of novel drug targets and for improvement of drug efficiency by analysing the effects of drugs on the robustness of cellular networks.Comment: This is an extended version of the Journal of Biology paper containing 2 Figures, 1 Table and 44 reference

Learning and innovative elements of strategy adoption rules expand cooperative network topologies

Cooperation plays a key role in the evolution of complex systems. However, the level of cooperation extensively varies with the topology of agent networks in the widely used models of repeated games. Here we show that cooperation remains rather stable by applying the reinforcement learning strategy adoption rule, Q-learning on a variety of random, regular, small-word, scale-free and modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove games. Furthermore, we found that using the above model systems other long-term learning strategy adoption rules also promote cooperation, while introducing a low level of noise (as a model of innovation) to the strategy adoption rules makes the level of cooperation less dependent on the actual network topology. Our results demonstrate that long-term learning and random elements in the strategy adoption rules, when acting together, extend the range of network topologies enabling the development of cooperation at a wider range of costs and temptations. These results suggest that a balanced duo of learning and innovation may help to preserve cooperation during the re-organization of real-world networks, and may play a prominent role in the evolution of self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3 Tables, 12 Figures and 116 reference

The Parameterized Complexity of Centrality Improvement in Networks

The centrality of a vertex v in a network intuitively captures how important v is for communication in the network. The task of improving the centrality of a vertex has many applications, as a higher centrality often implies a larger impact on the network or less transportation or administration cost. In this work we study the parameterized complexity of the NP-complete problems Closeness Improvement and Betweenness Improvement in which we ask to improve a given vertex' closeness or betweenness centrality by a given amount through adding a given number of edges to the network. Herein, the closeness of a vertex v sums the multiplicative inverses of distances of other vertices to v and the betweenness sums for each pair of vertices the fraction of shortest paths going through v. Unfortunately, for the natural parameter "number of edges to add" we obtain hardness results, even in rather restricted cases. On the positive side, we also give an island of tractability for the parameter measuring the vertex deletion distance to cluster graphs

ModuLand plug-in for Cytoscape: determination of hierarchical layers of overlapping network modules and community centrality

Summary: The ModuLand plug-in provides Cytoscape users an algorithm for determining extensively overlapping network modules. Moreover, it identifies several hierarchical layers of modules, where meta-nodes of the higher hierarchical layer represent modules of the lower layer. The tool assigns module cores, which predict the function of the whole module, and determines key nodes bridging two or multiple modules. The plug-in has a detailed JAVA-based graphical interface with various colouring options. The ModuLand tool can run on Windows, Linux, or Mac OS. We demonstrate its use on protein structure and metabolic networks. Availability: The plug-in and its user guide can be downloaded freely from: http://www.linkgroup.hu/modules.php. Contact: [email protected] Supplementary information: Supplementary information is available at Bioinformatics online.Comment: 39 pages, 1 figure and a Supplement with 9 figures and 10 table

Perturbation Centrality and Turbine: A Novel Centrality Measure Obtained Using a Versatile Network Dynamics Tool

Analysis of network dynamics became a focal point to understand and predict changes of complex systems. Here we introduce Turbine, a generic framework enabling fast simulation of any algorithmically definable dynamics on very large networks. Using a perturbation transmission model inspired by communicating vessels, we define a novel centrality measure: perturbation centrality. Hubs and inter-modular nodes proved to be highly efficient in perturbation propagation. High perturbation centrality nodes of the Met-tRNA synthetase protein structure network were identified as amino acids involved in intra-protein communication by earlier studies. Changes in perturbation centralities of yeast interactome nodes upon various stresses well recapitulated the functional changes of stressed yeast cells. The novelty and usefulness of perturbation centrality was validated in several other model, biological and social networks. The Turbine software and the perturbation centrality measure may provide a large variety of novel options to assess signaling, drug action, environmental and social interventions. The Turbine algorithm is available at: http://www.turbine.linkgroup.huComment: 21 pages, 4 figues, 1 table, 58 references + a Supplement of 52 pages, 10 figures, 9 tables and 39 references; Turbine algorithm is available at: http://www.turbine.linkgroup.h

Self-organization towards optimally interdependent networks by means of coevolution

Coevolution between strategy and network structure is established as a means to arrive at the optimal conditions needed to resolve social dilemmas. Yet recent research has highlighted that the interdependence between networks may be just as important as the structure of an individual network. We therefore introduce the coevolution of strategy and network interdependence to see whether this can give rise to elevated levels of cooperation in the prisonerʼs dilemma game. We show that the interdependence between networks self-organizes so as to yield optimal conditions for the evolution of cooperation. Even under extremely adverse conditions, cooperators can prevail where on isolated networks they would perish. This is due to the spontaneous emergence of a two-class society, with only the upper class being allowed to control and take advantage of the interdependence. Spatial patterns reveal that cooperators, once arriving at the upper class, are much more competent than defectors in sustaining compact clusters of followers. Indeed, the asymmetric exploitation of interdependence confers to them a strong evolutionary advantage that may resolve even the toughest of social dilemmas

Degeneracy: a link between evolvability, robustness and complexity in biological systems

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability