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At least 685 records · Page 38Linked to original sources
PubMed2002

Positive and negative feedback: striking a balance between necessary antagonists.

Most biological regulation systems comprise feedback circuits as crucial components. Negative feedback circuits have been well understood for a very long time; indeed, their understanding has been the basis for the engineering of cybernetic machines exhibiting stable behaviour. The importance of positive feedback circuits, considered as "vicious circles", has however been underestimated. In this article, we give a demonstration based on degree theory for vector fields of the conjecture, made by René Thomas, that the presence of positive feedback circuits is a necessary condition for autonomous differential systems, covering a wide class of biologically relevant systems, to possess multiple steady states. We also show ways to derive constraints on the weights of positive and negative feedback circuits. These qualitative and quantitative results provide, respectively, structural constraints (i.e. related to the interaction graph) and numerical constraints (i.e. related to the magnitudes of the interactions) on systems exhibiting complex behaviours, and should make it easier to reverse-engineer the interaction networks animating those systems on the basis of partial, sometimes unreliable, experimental data. We illustrate these concepts on a model multistable switch, in the context of cellular differentiation, showing a requirement for sufficient cooperativity. Further developments are expected in the discovery and modelling of regulatory networks in general, and in the interpretation of bio-array hybridization and proteomics experiments in particular.

Animals↗
PubMed2006

Percolation in living neural networks.

We study living neural networks by measuring the neurons' response to a global electrical stimulation. Neural connectivity is lowered by reducing the synaptic strength, chemically blocking neurotransmitter receptors. We use a graph-theoretic approach to show that the connectivity undergoes a percolation transition. This occurs as the giant component disintegrates, characterized by a power law with an exponent beta approximately or = 0.65. Beta is independent of the balance between excitatory and inhibitory neurons and indicates that the degree distribution is Gaussian rather than scale free.

Animals↗
PubMed2000

Flexibility and critical hydrogen bonds in cytochrome c.

We show that protein flexibility can be characterized using graph theory, from a single protein conformation. Covalent and hydrogen bonds are modeled by distance and angular constraints, and a map is constructed of the regions in this network that are flexible or rigid, based on whether their dihedral bonds remain rotatable or are locked by other interactions in the network. This analysis takes only a second on a typical PC, and interatomic potentials; the most time-consuming aspect of molecular dynamics calculations, are not required. Our preliminary work has shown that this approach identifies the experimentally observed, biologically important flexible regions in HIV protease and lysine-arginine-ornithine binding protein. Here we analyze three evolutionarily distant cytochromes c, and find strong similarity between their flexible regions, despite having only 39% sequence identity. Furthermore, we show how the structural flexibility increases as the weaker hydrogen bonds are removed, as would happen under thermal denaturation of the protein. This approach identifies the critical hydrogen bonds that cross-link the tertiary structure.

Amino Acid Sequence↗
PubMed1987

Analysis of adenomatous structures in histopathology.

A new idea of structure analysis in histopathology based upon first-order and third-order structures is presented. Networks formed by single cells and by tubulopapillary formations in adenomatous tissue were analyzed. The algorithm applied is based on the neighborhood conditions defined by O'Callaghan, using graph theory procedures. Twenty cases each of healthy colon mucosa, tubulovillous adenomas and highly to moderately differentiated adenocarcinomas of colon plus ten cases of mesotheliomas and ten cases of adenocarcinomas metastatic to the pleura were analyzed. Statistically significant differences were found in the cyclomatic number of neighboring elements. Classification of specimens of colon mucosa using discriminant analysis yielded correct results in 85% of the 20 cases. All ten cases of metastatic adenocarcinoma and nine of the ten cases of mesothelioma were also correctly classified by the same procedure. A trial of prospective diagnostic assistance in routine histology based upon these cases gave correct classification of three mesotheliomas and of two adenocarcinomas. The procedures are now being used successfully in the routine diagnosis of pleural epithelial/biphasic mesothelioma and of pleuritis carcinomatosa.

Adenocarcinoma↗
PubMed2002

Automatic recognition of cortical sulci of the human brain using a congregation of neural networks.

This paper describes a complete system allowing automatic recognition of the main sulci of the human cortex. This system relies on a preprocessing of magnetic resonance images leading to abstract structural representations of the cortical folding patterns. The representation nodes are cortical folds, which are given a sulcus name by a contextual pattern recognition method. This method can be interpreted as a graph matching approach, which is driven by the minimization of a global function made up of local potentials. Each potential is a measure of the likelihood of the labelling of a restricted area. This potential is given by a multi-layer perceptron trained on a learning database. A base of 26 brains manually labelled by a neuroanatomist is used to validate our approach. The whole system developed for the right hemisphere is made up of 265 neural networks. The mean recognition rate is 86% for the learning base and 76% for a generalization base, which is very satisfying considering the current weak understanding of the variability of the cortical folding patterns.

Artificial Intelligence↗
PubMed1996

A knowledge-based model construction approach to medical decision making.

We present a framework for representing the probabilistic effects of actions and contingent treatment plans. Our language has a well-defined declarative semantics and we have developed an implemented algorithm (named BNG) that generates Bayesian networks (BN) to compute the posterior probabilities of queries. In this paper we address the problem of projecting a contingent treatment plan by automatically constructing a structure of interrelated BNs, which we call a BN-graph, and applying the available propagation procedures on it. To address the optimal plan generation, we base our approach on the observation that normally the target plan space has a well-defined structure. We provide a language to describe plan spaces which resembles a programming language with loops and conditionals. We briefly present the procedures for finding the optimal plan(s) from such specified plan spaces.

Acute Disease↗
PubMed1993

A PC-based on-line system for physiological in vivo and in vitro experiments.

A PC-based system for data acquisition, control of experiments and analysis of physiological signals has been developed. The system has a flexibility that makes it useful for many different types of study, e.g. hemodynamics, electrophysiology and in vitro studies of organ contractile functions. The experimental set-up is specified in a number of tables, which can be modified with a table editor. The specifications can be stored in file and used for other experiments with an identical experimental set-up. The recording of data can be done either intermittently or continuously, and the intermittent recordings are initiated automatically at predefined times, or manually. With a tape recorder utility, data can be recorded during an experiment and analyzed at a later time. The signal analysis module has a high degree of flexibility, achieved by parameters defining preprocessing, heartbeat detection, heartbeat selection and analysis. Data is presented on the display in three types of window, showing phasic signals, derived parameters in trend graphs and derived parameters in numerical form. Data is saved on disk in two types of file: sampled raw data or derived parameters (ASCII file). An Ethernet-based network is used to send data to a VAX cluster, where it is further processed in RS/1 or the BIOLAB analysis program. The source code has been written in Ada, and the compiler generated a 32-bit code, which facilitated the development of a large program with large data buffers.

Electronic Data Processing↗
PubMed2001

Physicochemical and graph theoretical descriptors in developmental toxicity SAR: a comparative study.

Chemical insults to the developing fetus can lead to growth retardation, malformation, death, and functional deficits. The present study seeks to determine if physicochemical and/or graph theoretical parameters can be used to determine a structure-activity relationship (SAR) for developmental toxicity, and if consistency is observed among the selected features. The biological data utilized consists of a diverse series of compounds evaluated within the Chernoff-Kavlock in vivo mouse assay. Physicochemical parameters calculated correspond to electronic, steric, and transport properties. Graph theoretical parameters calculated include the simple, valence, and kappa indices. Both sets of parameters were independently applied to derive SARs in order to compare the quality of the respective models. Multiple random sampling, without replacement, was utilized to obtain ten training/test partitions. Models were built by linear discriminant analysis, decision trees, and neural networks respectively. Comparisons on identical sets of data were carried out to determine if any of the model building procedures had a significant advantage in terms of predictive performance. Furthermore, comparison of the features selected within and across the model building processes led to the determination of model consistency. Our results indicate that consistent features related to developmental toxicity are observed and that both physicochemical and graph theoretical parameters have equal utility.

Animals↗
PubMedDate not supplied

Symbolic anatomic knowledge representation in the Read Codes version 3: structure and application.

The Read Thesaurus (Version 3 of the Read Codes) is a controlled medical vocabulary produced during the Clinical Terms Projects with the involvement of over 2,000 health care professionals from all United Kingdom specialties. In addition to allowing the transfer of clinical information in a meaningful way, it supports analysis of this information and provides a basis for the development of shareable medical knowledge bases. The thesaurus includes a comprehensive, dynamic set of over 7,000 gross anatomic concepts richly linked in a network with over 16,000 operative procedures and 40,000 disorders. The representation of anatomic concepts aims to balance the requirements for expressivity, clearness, and simplicity. The underlying directed acyclic graph hierarchy is independent of the alphanumeric code and enables continued refinement and expansion. A template table allows semantic definition, qualification, and linkage of concepts.

Anatomy↗
PubMedDate not supplied

Towards more biological mutation operators in gene regulation studies.

Genetic regulation is often viewed as a complex system whose properties emerge from the interaction of regulatory genes. One major paradigm for studying the complex dynamics of gene regulation uses directed graphs to explore structure, behaviour and evolvability. Mutation operators used in such studies typically involve the insertion and deletion of nodes, and the insertion, deletion and rewiring of links at the network level. These network-level mutational operators are sufficient to allow the statistical analysis of network structure, but impose limitations on the way networks are evolved. There are a wide variety of mutations in DNA sequences that have yet to be analysed for their network-level effects. By modelling an artificial genome at the level of nucleotide sequences and mapping it to a regulatory network, biologically grounded mutation operators can be mapped to network-level mutations. This paper analyses five such sequence level mutations (single-point mutation, transposition, inversion, deletion and gene duplication) for their effects at the network level. Using analytic and simulation techniques, we show that it is rarely the case that nodes and links are cleanly added or deleted, with even the simplest point mutation causing a wide variety of network-level modifications. As expected, the vast majority of simple (single-point) mutations are neutral, resulting in a neutral plateau from which a range of functional behaviours can be reached. By analysing the effects of sequence-level mutations at the network level of gene regulation, we aim to stimulate more careful consideration of mutation operators in gene regulation models than has previously been given.

Algorithms↗
PubMed1997

From visual affordances in monkey parietal cortex to hippocampo-parietal interactions underlying rat navigation.

This paper explores the hypothesis that various subregions (but by no means all) of the posterior parietal cortex are specialized to process visual information to extract a variety of affordances for behaviour. Two biologically based models of regions of the posterior parietal cortex of the monkey are introduced. The model of the lateral intraparietal area (LIP) emphasizes its roles in dynamic remapping of the representation of targets during a double saccade task, and in combining stored, updated input with current visual input. The model of the anterior intraparietal area (AIP) addresses parietal-premotor interactions involved in grasping, and analyses the interaction between the AIP and premotor area F5. The model represents the role of other intraparietal areas working in concert with the inferotemporal cortex as well as with corollary discharge from F5 to provide and augment the affordance information in the AIP, and suggests how various constraints may resolve the action opportunities provided by multiple affordances. Finally, a systems-level model of hippocampo parietal interactions underlying rat navigation is developed, motivated by the monkey data used in developing the above two models as well as by data on neurones in the posterior parietal cortex of the monkey that are sensitive to visual motion. The formal similarity between dynamic remapping (primate saccades) and path integration (rat navigation) is noted, and certain available data on rat posterior parietal cortex in terms of affordances for locomotion are explained. The utility of further modelling, linking the World Graph model of cognitive maps for motivated behaviour with hippocampal-parietal interactions involved in navigation, is also suggested. These models demonstrate that posterior parietal cortex is not only itself a network of interacting subsystems, but functions through cooperative computation with many other brain regions.

Animals↗
PubMed2003

Origin of degree correlations in the Internet and other networks.

It has been argued that the observed anticorrelation between the degrees of adjacent vertices in the network representation of the Internet has its origin in the restriction that no two vertices have more than one edge connecting them. Here, we propose a formalism for modeling ensembles of graphs with single edges only and derive values for the exponents and correlation coefficients characterizing them. Our results confirm that the conjectured mechanism does indeed give rise to correlations of the kind seen in the Internet, although only a part of the measured correlation can be accounted for in this way.

Journal Article↗
PubMed2001

Biomedical image skeletonization: a novel method applied to fibrin network structures.

To understand the rheological behavior of fibrin clots, we must obtain quantitative measurements of morphometric parameters of the networks formed under various conditions. The networks are so complex that researchers must currently manually segment the images of network samples and estimate the parameters from them. Skeletonization is a promising tool for automating this task. We here propose a method that rapidly constructs a coarse representation of a skeleton graph and, using the snake model, deforms the graph to obtain smooth skeletons. Unlike many existing approaches, our method does not involve explicit object boundary information or high order derivatives. Since our method processes a given image as a whole, the presence of multiple objects in an image is automatically detected and the skeletons of these objects are computed simultaneously.

Algorithms↗
PubMed2006

Evaluation of clustering algorithms for protein-protein interaction networks.

BACKGROUND: Protein interactions are crucial components of all cellular processes. Recently, high-throughput methods have been developed to obtain a global description of the interactome (the whole network of protein interactions for a given organism). In 2002, the yeast interactome was estimated to contain up to 80,000 potential interactions. This estimate is based on the integration of data sets obtained by various methods (mass spectrometry, two-hybrid methods, genetic studies). High-throughput methods are known, however, to yield a non-negligible rate of false positives, and to miss a fraction of existing interactions. The interactome can be represented as a graph where nodes correspond with proteins and edges with pairwise interactions. In recent years clustering methods have been developed and applied in order to extract relevant modules from such graphs. These algorithms require the specification of parameters that may drastically affect the results. In this paper we present a comparative assessment of four algorithms: Markov Clustering (MCL), Restricted Neighborhood Search Clustering (RNSC), Super Paramagnetic Clustering (SPC), and Molecular Complex Detection (MCODE). RESULTS: A test graph was built on the basis of 220 complexes annotated in the MIPS database. To evaluate the robustness to false positives and false negatives, we derived 41 altered graphs by randomly removing edges from or adding edges to the test graph in various proportions. Each clustering algorithm was applied to these graphs with various parameter settings, and the clusters were compared with the annotated complexes. We analyzed the sensitivity of the algorithms to the parameters and determined their optimal parameter values. We also evaluated their robustness to alterations of the test graph. We then applied the four algorithms to six graphs obtained from high-throughput experiments and compared the resulting clusters with the annotated complexes. CONCLUSION: This analysis shows that MCL is remarkably robust to graph alterations. In the tests of robustness, RNSC is more sensitive to edge deletion but less sensitive to the use of suboptimal parameter values. The other two algorithms are clearly weaker under most conditions. The analysis of high-throughput data supports the superiority of MCL for the extraction of complexes from interaction networks.

Algorithms↗
PubMed2005

Alignment of metabolic pathways.

MOTIVATION: Several genome-scale efforts are underway to reconstruct metabolic networks for a variety of organisms. As the resulting data accumulates, the need for analysis tools increases. A notable requirement is a pathway alignment finder that enables both the detection of conserved metabolic pathways among different species as well as divergent metabolic pathways within a species. When comparing two pathways, the tool should be powerful enough to take into account both the pathway topology as well as the nodes' labels (e.g. the enzymes they denote), and allow flexibility by matching similar--rather than identical--pathways. RESULTS: MetaPathwayHunter is a pathway alignment tool that, given a query pathway and a collection of pathways, finds and reports all approximate occurrences of the query in the collection, ranked by similarity and statistical significance. It is based on a novel, efficient graph matching algorithm that extends the functionality of known techniques. The program also supports a visualization interface with which the alignment of two homologous pathways can be graphically displayed. We employed this tool to study the similarities and differences in the metabolic networks of the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae, as represented in highly curated databases. We reaffirmed that most known metabolic pathways common to both the species are conserved. Furthermore, we discovered a few intriguing relationships between pathways that provide insight into the evolution of metabolic pathways. We conclude with a description of biologically meaningful meta-queries, demonstrating the power and flexibility of our new tool in the analysis of metabolic pathways.

Animals↗
PubMed2003

Network landscape from a Brownian particle's perspective.

Given a complex biological or social network, how many clusters should it be decomposed into? We define the distance d(i,j) from node i to node j as the average number of steps a Brownian particle takes to reach j from i. Node j is a global attractor of i if d(i,j)< or =d(i,k) for any k of the graph; it is a local attractor of i if j in E(i) (the set of nearest neighbors of i) and d(i,j)< or =d(i,l) for any l in E(i). Based on the intuition that each node should have a high probability to be in the same community as its global (local) attractor on the global (local) scale, we present a simple method to uncover a network's community structure. This method is applied to several real networks and some discussion on its possible extensions is made.

Algorithms↗
PubMed1984

A method of schematic three-dimensional reconstruction for studying the gross morphology of epithelial residues in periodontal ligament.

A series of standardized black and white composite photomicrographs of serial sections at X 160 magnification were placed side by side to a straight reference line through the cementum margins. The distances of various parts of the epithelial rest system from the reference line were measured and from the measurements a bar graph was constructed which provided a 3-dimensional representation of the overall configuration of the marginally-sited rests and their relationship to the junctional epithelium. The epithelial residues formed a continuous network the coronal border of which was in intermittent direct continuity with the junctional epithelium. However, to what extent this was affected by the mild chronic inflammation present could not be assessed.

Animals↗
PubMed1997

Ant colonies for the travelling salesman problem.

We describe an artificial ant colony capable of solving the travelling salesman problem (TSP). Ants of the artificial colony are able to generate successively shorter feasible tours by using information accumulated in the form of a pheromone trail deposited on the edges of the TSP graph. Computer simulations demonstrate that the artificial ant colony is capable of generating good solutions to both symmetric and asymmetric instances of the TSP. The method is an example, like simulated annealing, neural networks and evolutionary computation, of the successful use of a natural metaphor to design an optimization algorithm.

Algorithms↗