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At least 487 records · Page 27Linked to original sources

Mean-field solution of the small-world network model.

The small-world network model is a simple model of the structure of social networks, which possesses characteristics of both regular lattices and random graphs. The model consists of a one-dimensional lattice with a low density of shortcuts added between randomly selected pairs of points. These shortcuts greatly reduce the typical path length between any two points on the lattice. We present a mean-field solution for the average path length and for the distribution of path lengths in the model. This solution is exact in the limit of large system size and either a large or small number of shortcuts.

Computer Simulation↗

Prediction of viable circular permutants using a graph theoretic approach.

MOTIVATION: In recent years graph-theoretic descriptions have been applied to aid the analysis of a number of complex biological systems. However, such an approach has only just begun to be applied to examine protein structures and the network of interactions between residues with promising results. Here we examine whether a graph measure known as closeness is capable of predicting regions where a protein can be split to form a viable circular permutant. Circular permutants are a powerful experimental tool to probe folding mechanisms and more recently have been used to design split enzyme reporter proteins. RESULTS: We test our method on an extensive set of experiments carried out on dihydrofolate reductase in which circular permutants were constructed for every amino acid position in the sequence, together with partial data from studies on other proteins. Results show that closeness is capable of correctly identifying significantly more residues which are suitable for circular permutation than solvent accessibility. This has potential implications for the design of successful split enzymes having particular importance for the development of protein-protein interaction screening methods and offers new perspectives on protein folding. More generally, the method illustrates the success with which graph-theoretic measures encapsulate the variety of long and short range interactions between residues during the folding process.

Binding Sites↗

Host-parasite models on graphs.

The behavior of two interacting populations "hosts" and "parasites" is investigated on Cayley trees and scale-free networks. In the former case analytical and numerical arguments elucidate a phase diagram for the susceptible-infected-susceptible model, whose most interesting feature is the absence of a tricritical point as a function of the two independent spreading parameters. For scale-free graphs, the parasite population can be described effectively by its dynamics in a host background. This is shown both by considering the appropriate dynamical equations and by numerical simulations on Barabási-Albert networks with the major implication that in the thermodynamic limit the critical parasite spreading parameter vanishes. Some implications and generalizations are discussed.

Animals↗

Sparse spectral graph analysis and its application to gastric cancer drug resistance-specific molecular interplays identification.

Uncovering acquired drug resistance mechanisms has garnered considerable attention as drug resistance leads to treatment failure and death in patients with cancer. Although several bioinformatics studies developed various computational methodologies to uncover the drug resistance mechanisms in cancer chemotherapy, most studies were based on individual or differential gene expression analysis. However the single gene-based analysis is not enough, because perturbations in complex molecular networks are involved in anti-cancer drug resistance mechanisms. The main goal of this study is to reveal crucial molecular interplay that plays key roles in mechanism underlying acquired gastric cancer drug resistance. To uncover the mechanism and molecular characteristics of drug resistance, we propose a novel computational strategy that identified the differentially regulated gene networks. Our method measures dissimilarity of networks based on the eigenvalues of the Laplacian matrix. Especially, our strategy determined the networks' eigenstructure based on sparse eigen loadings, thus, the only crucial features to describe the graph structure are involved in the eigenanalysis without noise disturbance. We incorporated the network biology knowledge into eigenanalysis based on the network-constrained regularization. Therefore, we can achieve a biologically reliable interpretation of the differentially regulated gene network identification. Monte Carlo simulations show the outstanding performances of the proposed methodology for differentially regulated gene network identification. We applied our strategy to gastric cancer drug-resistant-specific molecular interplays and related markers. The identified drug resistance markers are verified through the literature. Our results suggest that the suppression and/or induction of COL4A1, PXDN and TGFBI and their molecular interplays enriched in the Extracellular-related pathways may provide crucial clues to enhance the chemosensitivity of gastric cancer. The developed strategy will be a useful tool to identify phenotype-specific molecular characteristics that can provide essential clues to uncover the complex cancer mechanism.

Stomach Neoplasms↗

Small-world network organization of functional connectivity of EEG slow-wave activity during sleep.

OBJECTIVE: To analyze the functional connectivity patterns of the EEG slow-wave activity during the different sleep stages and Cyclic Alternating Pattern (CAP) conditions, using concepts derived from Graph Theory. METHODS: We evaluated spatial patterns of EEG slow-wave synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during the different sleep stages and CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s). RESULTS: Cp and Cp/Cp-s increased significantly from wakefulness to sleep while Lp and Lp/Lp-s did not show changes. Cp/Cp-s was higher for A1 phases, compared to B phases of CAP. CONCLUSIONS: The network organization of the EEG slow-wave synchronization during sleep shows features characteristic of small-world networks (high Cp combined with low Lp); this type of organization is slightly but significantly more evident during the CAP A1 subtypes. SIGNIFICANCE: Our results show feasibility of using graph theoretical measures to characterize the complexity of brain networks during sleep and might indicate sleep, and the A1 phases of CAP in particular, as a period during which slow-wave synchronization shows optimal network organization for information processing.

Adult↗

Assessing the effects of human mixing patterns on human immunodeficiency virus-1 interhost phylogenetics through social network simulation.

Geneticists seeking to understand HIV-1 evolution among human hosts generally assume that hosts represent a panmictic population. Social science research demonstrates that the network patterns over which HIV-1 spreads are highly nonrandom, but the effect of these patterns on the genetic diversity of HIV-1 and other sexually transmitted pathogens has yet to be thoroughly examined. In addition, interhost phylogenetic models rarely account explicitly for genetic diversity arising from intrahost dynamics. This study outlines a graph-theoretic framework (exponential random graph modeling, ERGM) for the estimation, inference, and simulation of dynamic partnership networks. This approach is used to simulate HIV-1 transmission and evolution under eight mixing patterns resembling those observed in empirical human populations, while simultaneously incorporating intrahost viral diversity. Models of parametric growth fit panmictic populations well, yielding estimates of total viral effective population on the order of the product of infected host size and intrahost effective viral population size. Populations exhibiting patterns of nonrandom mixing differ more widely in estimates of effective population size they yield, however, and reconstructions of population dynamics can exhibit severe errors if panmixis is assumed. I discuss implications for HIV-1 phylogenetics and the potential for ERGM to provide a general framework for addressing these issues.

Evolution, Molecular↗

Measures of concurrency in networks and the spread of infectious disease.

An investigation is made into the impact of concurrent partnerships on epidemic spread. Starting from a definition of concurrency on the level of individuals, the authors define ways to quantify concurrency on the population level. An index of concurrency based on graph theoretical considerations is introduced, and the way in which it is related to the degree distribution of the contact graph is demonstrated. Then the spread of an infectious disease on a dynamic partnership network is investigated. The model is based on a stochastic process of pair formation and separation and a process of disease transmission within partnerships of susceptible and infected individuals. Using Monte Carlo simulation, the spread of the epidemic is compared for contact patterns ranging from serial monogamy to situations where individuals can have many partners simultaneously. It is found that for a fixed mean number of partners per individual the distribution of these partnerships over the population has a major influence on the speed of the epidemic in its initial phase and consequently in the number of individuals who are infected after a certain time period.

Acquired Immunodeficiency Syndrome↗

Birth of scale-free molecular networks and the number of distinct DNA and protein domains per genome.

MOTIVATION: Current growth in the field of genomics has provided a number of exciting approaches to the modeling of evolutionary mechanisms within the genome. Separately, dynamical and statistical analyses of networks such as the World Wide Web and the social interactions existing between humans have shown that these networks can exhibit common fractal properties-including the property of being scale-free. This work attempts to bridge these two fields and demonstrate that the fractal properties of molecular networks are linked to the fractal properties of their underlying genomes. RESULTS: We suggest a stochastic model capable of describing the evolutionary growth of metabolic or signal-transduction networks. This model generates networks that share important statistical properties (so-called scale-free behavior) with real molecular networks. In particular, the frequency of vertices connected to exactly k other vertices follows a power-law distribution. The shape of this distribution remains invariant to changes in network scale: a small subgraph has the same distribution as the complete graph from which it is derived. Furthermore, the model correctly predicts that the frequencies of distinct DNA and protein domains also follow a power-law distribution. Finally, the model leads to a simple equation linking the total number of different DNA and protein domains in a genome with both the total number of genes and the overall network topology. AVAILABILITY: MatLab (MathWorks, Inc.) programs described in this manuscript are available on request from the authors. CONTACT: ar345@columbia.edu.

Biological Evolution↗

Defining and identifying communities in networks.

The investigation of community structures in networks is an important issue in many domains and disciplines. This problem is relevant for social tasks (objective analysis of relationships on the web), biological inquiries (functional studies in metabolic and protein networks), or technological problems (optimization of large infrastructures). Several types of algorithms exist for revealing the community structure in networks, but a general and quantitative definition of community is not implemented in the algorithms, leading to an intrinsic difficulty in the interpretation of the results without any additional nontopological information. In this article we deal with this problem by showing how quantitative definitions of community are implemented in practice in the existing algorithms. In this way the algorithms for the identification of the community structure become fully self-contained. Furthermore, we propose a local algorithm to detect communities which outperforms the existing algorithms with respect to computational cost, keeping the same level of reliability. The algorithm is tested on artificial and real-world graphs. In particular, we show how the algorithm applies to a network of scientific collaborations, which, for its size, cannot be attacked with the usual methods. This type of local algorithm could open the way to applications to large-scale technological and biological systems.

Algorithms↗

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis.

BACKGROUND: Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. RESULTS: Common fragile sites were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Moreover we showed how the internal organization of the graph in communities and even in very simple subgraphs can be a starting point for the identification of new factors of instability at common fragile sites. CONCLUSION: We developed a computational method addressing the fundamental issue of studying the functional content of common fragile sites. Our analysis integrated two different approaches. First, data on common fragile site expression were analyzed in a complex networks framework. Second, outcomes of the network statistical description served as sources for the functional annotation of genes at common fragile sites by means of the Gene Ontology vocabulary. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.

Cells, Cultured↗

Permanence of sparse catalytic networks.

Some global dynamical properties of catalytic networks, in particular permanence, are closely related with a directed graph representing the differential equation. It can be shown that for every directed graph with a Hamiltonian circuit there is a choice of rate constants such that the system is permanent. On the other hand, one can find properties of the graphs, for example, reducibility or the presence of endpoints, that are incompatible with permanence.

Biological Evolution↗

Stability of generalized topographic mappings between cell layers through correlational learning.

We propose a simple topographic mapping formation model from a cell layer to a cell layer. Our model is a discrete one in that the state value of input and output cells takes 0 or 1 and input and output layers are represented by undirected graphs. A binary input pattern can be given to the network consisting of input and output cell layers. Such an input pattern can be represented by a subset of input cells. That is, a state value of an input cell takes 1 if a cell belongs to the subset, otherwise, a state value of an input cell is 0. Such a definition of an input pattern does not necessarily assume a short-range excitatory mechanism in an input layer. Thus, a topographic mapping described in this model is a map, which preserves the input pattern relation. By using the concept of input pattern separability, we showed an existence condition of certain learning rules, which are correlational. We have paid special attention to such correlational type learning rules, and have shown under the rules that topographic mappings are the only stable ones. As to the non-correlational learning rules, we also investigate the stability of generated mappings.

Algorithms↗

Adaptive reconfiguration of fractal small-world human brain functional networks.

Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a finger-tapping task, whereas the other half were studied at rest. We found that brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical delta (low and high), , alpha, beta, and gamma frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2-37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency gamma network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both beta and gamma networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding. Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters.

Brain↗

Protein domain decomposition using a graph-theoretic approach.

MOTIVATION: Automatic decomposition of a multi-domain protein into individual domains represents a highly interesting and unsolved problem. As the number of protein structures in PDB is growing at an exponential rate, there is clearly a need for more reliable and efficient methods for protein domain decomposition simply to keep the domain databases up-to-date. RESULTS: We present a new algorithm for solving the domain decomposition problem, using a graph-theoretic approach. We have formulated the problem as a network flow problem, in which each residue of a protein is represented as a node of the network and each residue--residue contact is represented as an edge with a particular capacity, depending on the type of the contact. A two-domain decomposition problem is solved by finding a bottleneck (or a minimum cut) of the network, which minimizes the total cross-edge capacity, using the classical Ford--Fulkerson algorithm. A multi-domain decomposition problem is solved through repeatedly solving a series of two-domain problems. The algorithm has been implemented as a computer program, called DomainParser. We have tested the program on a commonly used test set consisting of 55 proteins. The decomposition results are 78.2% in agreement with the literature on both the number of decomposed domains and the assignments of residues to each domain, which compares favorably to existing programs. On the subset of two-domain proteins (20 in number), the program assigned 96.7% of the residues correctly when we require that the number of decomposed domains is two.

Algorithms↗

Scale-free network growth by ranking.

Network growth is currently explained through mechanisms that rely on node prestige measures, such as degree or fitness. In many real networks, those who create and connect nodes do not know the prestige values of existing nodes but only their ranking by prestige. We propose a criterion of network growth that explicitly relies on the ranking of the nodes according to any prestige measure, be it topological or not. The resulting network has a scale-free degree distribution when the probability to link a target node is any power-law function of its rank, even when one has only partial information of node ranks. Our criterion may explain the frequency and robustness of scale-free degree distributions in real networks, as illustrated by the special case of the Web graph.

Journal Article↗

Formation of regulatory patterns during signal propagation in a Mammalian cellular network.

We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways and cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through the system. Specification of input and output nodes allowed us to identify functional modules. Networking resulted in the emergence of regulatory motifs, such as positive and negative feedback and feedforward loops, that process information. Key regulators of plasticity were highly connected nodes required for the formation of regulatory motifs, indicating the potential importance of such motifs in determining cellular choices between homeostasis and plasticity.

Algorithms↗

DNA microarray data and contextual analysis of correlation graphs.

BACKGROUND: DNA microarrays are used to produce large sets of expression measurements from which specific biological information is sought. Their analysis requires efficient and reliable algorithms for dimensional reduction, classification and annotation. RESULTS: We study networks of co-expressed genes obtained from DNA microarray experiments. The mathematical concept of curvature on graphs is used to group genes or samples into clusters to which relevant gene or sample annotations are automatically assigned. Application to publicly available yeast and human lymphoma data demonstrates the reliability of the method in spite of its simplicity, especially with respect to the small number of parameters involved. CONCLUSIONS: We provide a method for automatically determining relevant gene clusters among the many genes monitored with microarrays. The automatic annotations and the graphical interface improve the readability of the data. A C++ implementation, called Trixy, is available from http://tagc.univ-mrs.fr/bioinformatics/trixy.html.

Algorithms↗

[Logical structure graphs in the teaching of oncology].

The graduates of medical institutes are the first link in the general therapy network, where all patients with pretumor and tumor lesions are referred to for medical aid. It is the rate of their training in oncology that the number of patients with advanced malignancies depends on. To improve the teaching of oncology the writers have used the graphs of logical system, which enabled not only the student but also the teacher to concentrate their attention on the key, basic problems, to choose the necessary information and to reject an excessive secondary one. The graphs of logic system allow the student to realize and understand the structure of the subject concerned, as a whole, the relationship of separate elements under study, thus being a visual aid contributing to better mastering the subject. The former offer good grounds for a scientific approach to the teaching problems.

Logic↗