arXiv subjects

Mate S. Szalay

Publications and source records attributed to Mate S. Szalay.

8 recordsLinked to original sources

arXiv2010

Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics

Background: Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult. Methodology/Principal Findings: Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics. Conclusions/Significance: The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.

physics.comp-ph↗

arXiv2008

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.

q-bio.MN↗

arXiv2008

Chaperones as integrators of cellular networks: Changes of cellular integrity in stress and diseases

Cellular networks undergo rearrangements during stress and diseases. In un-stressed state the yeast protein-protein interaction network (interactome) is highly compact, and the centrally organized modules have a large overlap. During stress several original modules became more separated, and a number of novel modules also appear. A few basic functions, such as the proteasome preserve their central position. However, several functions with high energy demand, such the cell-cycle regulation loose their original centrality during stress. A number of key stress-dependent protein complexes, such as the disaggregation-specific chaperone, Hsp104, gain centrality in the stressed yeast interactome. Molecular chaperones, heat shock, or stress proteins form complex interaction networks (the chaperome) with each other and their partners. Here we show that the human chaperome recovers the segregation of protein synthesis-coupled and stress-related chaperones observed in yeast recently. Examination of yeast and human interactomes shows that (1) chaperones are inter-modular integrators of protein-protein interaction networks, which (2) often bridge hubs and (3) are favorite candidates for extensive phosphorylation. Moreover, chaperones (4) become more central in the organization of the isolated modules of the stressed yeast protein-protein interaction network, which highlights their importance in the de-coupling and re-coupling of network modules during and after stress. Chaperone-mediated evolvability of cellular networks may play a key role in cellular adaptation during stress and various polygenic and chronic diseases, such as cancer, diabetes or neurodegeneration.

q-bio.MN↗

arXiv2007

Stress-induced rearrangements of cellular networks: consequences for protection and drug design

The complexity of the cells can be described and understood by a number of networks such as protein-protein interaction, cytoskeletal, organelle, signalling, gene transcription and metabolic networks. All these networks are highly dynamic producing continuous rearrangements in their links, hubs, network-skeleton and modules. Here we describe the adaptation of cellular networks after various forms of stress causing perturbations, congestions and network damage. Chronic stress decreases link-density, decouples or even quarantines modules, and induces an increased competition between network hubs and bridges. Extremely long or strong stress may induce a topological phase transition in the respective cellular networks, which switches the cell to a completely different mode of cellular function. We summarize our initial knowledge on network restoration after stress including the role of molecular chaperones in this process. Finally, we discuss the implications of stress-induced network rearrangements in diseases and ageing, and propose therapeutic approaches both to increase the robustness and help the repair of cellular networks.

q-bio.MN↗

arXiv2007

Network analysis of protein dynamics

The network paradigm is increasingly used to describe the topology and dynamics of complex systems. Here we review the results of the topological analysis of protein structures as molecular networks describing their small-world character, and the role of hubs and central network elements in governing enzyme activity, allosteric regulation, protein motor function, signal transduction and protein stability. We summarize available data how central network elements are enriched in active centers and ligand binding sites directing the dynamics of the entire protein. We assess the feasibility of conformational and energy networks to simplify the vast complexity of rugged energy landscapes and to predict protein folding and dynamics. Finally, we suggest that modular analysis, novel centrality measures, hierarchical representation of networks and the analysis of network dynamics will soon lead to an expansion of this field.

q-bio.BM↗

arXiv2007

How to design multi-target drugs: Target search options in cellular networks

Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade. Multi-target drugs multiply the number of pharmacologically relevant target molecules by introducing a set of indirect, network-dependent effects. Parallel with this the low-affinity binding of multi-target drugs eases the constraints of druggability, and significantly increases the size of the druggable proteome. These effects tremendously expand the number of potential drug targets, and will introduce novel classes of multi-target drugs with smaller side effects and toxicity. Here we review the recent progress in this field, compare possible network attack strategies, and propose several methods to find target-sets for multi-target drugs.

q-bio.MN↗

arXiv2007

Molecular chaperones: The modular evolution of cellular networks

Molecular chaperones play a prominent role in signaling and transcriptional regulatory networks of the cell. Recent advances uncovered that chaperones act as genetic buffers stabilizing the phenotype of various cells and organisms and may serve as potential regulators of evolvability. Chaperones have weak links, connect hubs, are in the overlaps of network modules and may uncouple these modules during stress, which gives an additional protection for the cell at the network-level. Moreover, after stress chaperones are essential to re-build inter-modular contacts by their low affinity sampling of the potential interaction partners in different modules. This opens the way to the chaperone-regulated modular evolution of cellular networks, and helps us to design novel therapeutic and anti-aging strategies.

q-bio.MN↗

arXiv2005

Water and molecular chaperones act as weak links of protein folding networks: energy landscape and punctuated equilibrium changes point towards a game theory of proteins

Water molecules and molecular chaperones efficiently help the protein folding process. Here we describe their action in the context of the energy and topological networks of proteins. In energy terms water and chaperones were suggested to decrease the activation energy between various local energy minima smoothing the energy landscape, rescuing misfolded proteins from conformational traps and stabilizing their native structure. In kinetic terms water and chaperones may make the punctuated equilibrium of conformational changes less punctuated and help protein relaxation. Finally, water and chaperones may help the convergence of multiple energy landscapes during protein-macromolecule interactions. We also discuss the possibility of the introduction of protein games to narrow the multitude of the energy landscapes when a protein binds to another macromolecule. Both water and chaperones provide a diffuse set of rapidly fluctuating weak links (low affinity and low probability interactions), which allow the generalization of all these statements to a multitude of networks.

q-bio.BM↗