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PubMed2005

Load characterization and anomaly detection for voice over IP traffic.

We consider the problem of traffic anomaly detection in IP networks. Traffic anomalies typically arise when there is focused overload or when a network element fails and it is desired to infer these purely from the measured traffic. We derive new general formulae for the variance of the cumulative traffic over a fixed time interval and show how the derived analytical expression simplifies for the case of voice over IP traffic, the focus of this paper. To detect load anomalies, we show it is sufficient to consider cumulative traffic over relatively long intervals such as 5 min. We also propose simple anomaly detection tests including detection of over/underload. This approach substantially extends the current practice in IP network management where only the first-order statistics and fixed thresholds are used to identify abnormal behavior. We conclude with the application of the scheme to field data from an operational network.

Algorithms↗

PubMed2006

Reverse engineering the gap gene network of Drosophila melanogaster.

A fundamental problem in functional genomics is to determine the structure and dynamics of genetic networks based on expression data. We describe a new strategy for solving this problem and apply it to recently published data on early Drosophila melanogaster development. Our method is orders of magnitude faster than current fitting methods and allows us to fit different types of rules for expressing regulatory relationships. Specifically, we use our approach to fit models using a smooth nonlinear formalism for modeling gene regulation (gene circuits) as well as models using logical rules based on activation and repression thresholds for transcription factors. Our technique also allows us to infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of models to test several outstanding questions about gap gene regulation, including regulation of and by hunchback and the role of autoactivation. Based on our modeling results and validation against the experimental literature, we propose a revised network structure for the gap gene system. Interestingly, some relationships in standard textbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expression during wild-type development.

Animals↗

PubMed2003

In silico analysis reveals substantial variability in the gene contents of the gamma proteobacteria LexA-regulon.

MOTIVATION: Motif-prediction algorithm capabilities for the analysis of bacterial regulatory networks and the prediction of new regulatory sites can be greatly enhanced by the use of comparative genomics approaches. In this study, we make use of a consensus-building algorithm and comparative genomics to conduct an in-depth analysis of the LexA-regulon of gamma proteobacteria, and we use the inferred results to study the evolution of this regulatory network and to examine the usefulness of the control sequences and gene contents of regulons in phylogenetic analysis. RESULTS: We show, for the first time, the substantial heterogeneity that the LexA-regulon of gamma proteobacteria displays in terms of gene content and we analyze possible branching points in its evolution. We also demonstrate the feasibility of using regulon-related information to derive sound phylogenetic inferences. AVAILABILITY: Complementary analysis data and both the source code and the Windows-executable files of the consensus-building software are available at http://www.cnm.es/~ivan/RCGScanner/

Algorithms↗

PubMed2001

T-REX: reconstructing and visualizing phylogenetic trees and reticulation networks.

UNLABELLED: T-REX (tree and reticulogram reconstruction) is an application to reconstruct phylogenetic trees and reticulation networks from distance matrices. The application includes a number of tree fitting methods like NJ, UNJ or ADDTREE which have been very popular in phylogenetic analysis. At the same time, the software comprises several new methods of phylogenetic analysis such as: tree reconstruction using weights, tree inference from incomplete distance matrices or modeling a reticulation network for a collection of objects or species. T-REX also allows the user to visualize obtained tree or network structures using Hierarchical, Radial or Axial types of tree drawing and manipulate them interactively. AVAILABILITY: T-REX is a freeware package available online at: http://www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex

Algorithms↗

PubMed2026

Schizophrenia and bipolar disorder: a comparative analysis of genetic and brain network connectivity.

BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision. METHODS: Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder. RESULTS: Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates. CONCLUSION: These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Humans↗

PubMed2000

Visuo-tactile cross-modal associations in cortical somatosensory cells.

Recent studies show that cells in the somatosensory cortex are involved in the short-term retention of tactile information. In addition, some somatosensory cells appear to retain visual information that has been associated with the touch of an object. The presence of such cells suggests that nontactile stimuli associated with touch have access to cortical neuron networks engaged in the haptic sense. Thus, we inferred that somatosensory cells would respond to behaviorally associated visual and tactile stimuli. To test this assumption, single units were recorded from the anterior parietal cortex (Brodmann's areas 3a, 3b, 1, and 2) of monkeys performing a visuo-haptic delay task, which required the memorization of a visual cue for a tactile choice. Most cells responding to that cue responded also to the corresponding object presented for tactile choice. Significant correlations were observed in some cells between their differential reactions to tactile objects and their differential reactions to the associated visual cues. Some cells were recorded in both the cross-modal task and a haptic unimodal task, where the animal had to retain a tactile cue for a tactile choice. In most of these cells, correlations were observed between stimulus-related firing in corresponding cue periods of the two tasks. These findings suggest that cells in somatosensory cortex are the components of neuronal networks representing tactile information. Associated visual stimuli may activate such networks through visuo-haptic associations established by behavioral training.

Animals↗

PubMed2025

Genotype by Environment Interactions in Gene Regulation Underlie the Response to Soil Drying in the Model Grass Brachypodium distachyon.

Gene expression is a quantitative trait under the control of genetic and environmental factors and their interaction, so-called genotype and environment (G × E). Understanding the mechanisms driving G × E is fundamental for ensuring stable crop performance across environments and for predicting the response of natural populations to climate change. Gene expression is regulated through complex molecular networks, yet the interactions between genotype and environment in gene regulation are rarely considered, particularly at the genome scale. Current frameworks and experimental designs often lack power to explicitly test network rewiring or to systematically compare regulatory networks. Here, we leverage a highly replicated RNA-sequencing dataset to model genome-scale gene expression variation between two natural accessions of the model grass Brachypodium distachyon and their response to soil drying. We first identified genotypic, environmental, and G × E effects on physiological, metabolic, and gene expression traits. We identify patterns of conservation-or variation-in gene coexpression networks and link these coexpression features to physiological traits. We further develop predictions of gene-gene interactions using causal inference and screen for interactions specific to-or with higher affinity in-a single genotype, treatment, or their interaction, G × E. Our analyses identify variation in candidate gene regulatory networks that may shape the evolution of environmental response in B. distachyon. We highlight the environmentally dependent regulatory control of several metabolic traits shown previously to play a role in drought acclimation. The framework presented here provides a scalable approach for more complex comparisons, particularly with the growing availability of large datasets from technologies such as single-cell transcriptomics.

Brachypodium↗

PubMed2004

Reconstruction of gene networks using Bayesian learning and manipulation experiments.

MOTIVATION: The analysis of high-throughput experimental data, for example from microarray experiments, is currently seen as a promising way of finding regulatory relationships between genes. Bayesian networks have been suggested for learning gene regulatory networks from observational data. Not all causal relationships can be inferred from correlation data alone. Often several equivalent but different directed graphs explain the data equally well. Intervention experiments where genes are manipulated can help to narrow down the range of possible networks. RESULTS: We describe an active learning algorithm that suggests an optimized sequence of intervention experiments. Simulation experiments show that our selection scheme is better than an unguided choice of interventions in learning the correct network and compares favorably in running time and results with methods based on value of information calculations.

Algorithms↗

PubMed2006

Identification and analysis of evolutionarily cohesive functional modules in protein networks.

The increasing number of sequenced genomes makes it possible to infer the evolutionary history of functional modules, i.e., groups of proteins that contribute jointly to the same cellular function in a given species. Here we identify and analyze those prokaryotic functional modules, whose composition remains largely unchanged during evolution, and study their properties. Such "cohesive" modules have a large number of internal functional connections, encode genes that tend to be in close proximity in prokaryotic genomes, and correspond to physical complexes or complex functional systems like the flagellar apparatus. Cohesive modules are enriched in processes such as energy and amino acid metabolism, cell motility, and intracellular trafficking, or secretion. By grouping genes into modules we achieve a more precise estimate of their age and find that the young modules are often horizontally transferred between species and are enriched in functions involved in interactions with the environment, implying that they play an important role in the adaptation of species to new environments.

Computational Biology↗

PubMed2005

FiatFlux--a software for metabolic flux analysis from 13C-glucose experiments.

BACKGROUND: Quantitative knowledge of intracellular fluxes is important for a comprehensive characterization of metabolic networks and their functional operation. In contrast to direct assessment of metabolite concentrations, in vivo metabolite fluxes must be inferred indirectly from measurable quantities in 13C experiments. The required experience, the complicated network models, large and heterogeneous data sets, and the time-consuming set-up of highly controlled experimental conditions largely restricted metabolic flux analysis to few expert groups. A conceptual simplification of flux analysis is the analytical determination of metabolic flux ratios exclusively from MS data, which can then be used in a second step to estimate absolute in vivo fluxes. RESULTS: Here we describe the user-friendly software package FiatFlux that supports flux analysis for non-expert users. In the first module, ratios of converging fluxes are automatically calculated from GC-MS-detected 13C-pattern in protein-bound amino acids. Predefined fragmentation patterns are automatically identified and appropriate statistical data treatment is based on the comparison of redundant information in the MS spectra. In the second module, absolute intracellular fluxes may be calculated by a 13C-constrained flux balancing procedure that combines experimentally determined fluxes in and out of the cell and the above flux ratios. The software is preconfigured to derive flux ratios and absolute in vivo fluxes from [1-13C] and [U-13C]glucose experiments and GC-MS analysis of amino acids for a variety of microorganisms. CONCLUSION: FiatFlux is an intuitive tool for quantitative investigations of intracellular metabolism by users that are not familiar with numerical methods or isotopic tracer experiments. The aim of this open source software is to enable non-specialists to adapt the software to their specific scientific interests, including other 13C-substrates, labeling mixtures, and organisms.

Bacteria↗

PubMed1994

Rule extraction with fuzzy neural network.

This paper deals with the learning of understandable decision rules with connectionist systems. Our approach consists of extracting fuzzy control rules with a new fuzzy neural network. Whereas many other works on this area propose to use combinations of nonlinear neurons to approximate fuzzy operations, we use a fuzzy neuron that computes max-min operations. Thus, this neuron can be interpreted as a possibility estimator, just as sigma-pi neurons can support a probabilistic interpretation. Within this context, possibilistic inferences can be drawn through the multi-layered network, using a distributed representation of the information. A new learning procedure has been developed in order that each part of the network can be learnt sequentially, while other parts are frozen. Each step of the procedure is based on the same kind of learning scheme: the backpropagation of a well-chosen cost function with appropriate derivatives of max-min function. An appealing result of the learning phase is the ability of the network to automatically reduce the number of the condition-parts of the rules, if needed. The network has been successfully tested on the learning of a control rule base for an inverted pendulum.

Artificial Intelligence↗

PubMed2004

Growing genetic regulatory networks from seed genes.

MOTIVATION: A number of models have been proposed for genetic regulatory networks. In principle, a network may contain any number of genes, so long as data are available to make inferences about their relationships. Nevertheless, there are two important reasons why the size of a constructed network should be limited. Computationally and mathematically, it is more feasible to model and simulate a network with a small number of genes. In addition, it is more likely that a small set of genes maintains a specific core regulatory mechanism. RESULTS: Subnetworks are constructed in the context of a directed graph by beginning with a seed consisting of one or more genes believed to participate in a viable subnetwork. Functionalities and regulatory relationships among seed genes may be partially known or they may simply be of interest. Given the seed, we iteratively adjoin new genes in a manner that enhances subnetwork autonomy. The algorithm is applied using both the coefficient of determination and the Boolean-function influence among genes, and it is illustrated using a glioma gene-expression dataset. AVAILABILITY: Software for the seed-growing algorithm will be available at the website for Probabilistic Boolean Networks: http://www2.mdanderson.org/app/ilya/PBN/PBN.htm

Algorithms↗

PubMed2005

Inferring figure-ground using a recurrent integrate-and-fire neural circuit.

Several theories of early visual perception hypothesize neural circuits that are responsible for assigning ownership of an object's occluding contour to a region which represents the "figure." Previously, we have presented a Bayesian network model which integrates multiple cues and uses belief propagation to infer local figure-ground relationships along an object's occluding contour. In this paper, we use a linear integrate-and-fire model to demonstrate how such inference mechanisms could be carried out in a biologically realistic neural circuit. The circuit maps the membrane potentials of individual neurons to log probabilities and uses recurrent connections to represent transition probabilities. The network's "perception" of figure-ground is demonstrated for several examples, including perceptually ambiguous figures, and compared qualitatively and quantitatively with human psychophysics.

Action Potentials↗

PubMedDate not supplied

Methodology for a medical expert system on fuzzy analog ganglionar lattices. Non-approximate reasoning with multiple antecendents of different relative importance and limited uncertainty.

This work presents an Expert System based on fuzzy analog ganglionar lattices. Its reasoning scheme is designed analogously to the expert's mental organization and it is realized on an (analog) operator called the ganglionar lattice. It is a connectionist system that uses the medical knowledge to define its architecture. The operator evokes some similarities to higher order neural networks and performs as the knowledge base and inference engine of the expert system, in a unified manner. A main feature of this operator is that it exhibits the variables corresponding to all intermediate concepts identified by the expert; this characteristic is shown to be most valuable for assessing, explicating and prospecting in medical applications. Further, it is capable of (i) evaluating a consequent for a variety of non-approximate reasonings with multiple antecendents of different relative importance under limited uncertainty; (ii) explicating the conclusions at different levels of abstraction to suit the user; and (iii) prospecting for the best 'a priori' sequence of unevaluated antecedents, from which to choose following tests. These procedures are based on the objective criterion of the consequent's uncertainty decrease (entropy). All results are produced in numerical form and may be translated into restricted natural language. A simple example of this technology is fully developed. Finally the method's potentials are discussed for future applications.

Artificial Intelligence↗

PubMed2000

Controlling activity fluctuations in large, sparsely connected random networks.

Controlling activity in recurrent neural network models of brain regions is essential both to enable effective learning and to reproduce the low activities that exist in some cortical regions such as hippocampal region CA3. Previous studies of sparse, random, recurrent networks constructed with McCulloch-Pitts neurons used probabilistic arguments to set the parameters that control activity. Here, we extend this work by adding an additional, biologically appropriate, parameter to control the magnitude and stability of activity oscillations. The new constant can be considered to be the rest conductance in a shunting model or the threshold when subtractive inhibition is used. This new parameter is critical for large networks run at low activity levels. Importantly, extreme activity fluctuations that act to turn large networks totally on or totally off can now be avoided. We also show how the size of external input activity interacts with this parameter to affect network activity. Then the model based on fixed weights is extended to estimate activities in networks with distributed weights. Because the theory provides accurate control of activity fluctuations, the approach can be used to design a predictable amount of pseudorandomness into deterministic networks. Such nonminimal fluctuations improve learning in simulations trained on the transitive inference problem.

Computer Simulation↗

PubMed1996

Connectionist modeling of the recovery of language functions following brain damage.

This paper reviews the contribution of connectionism to our understanding of behavioral changes in language functions after brain damage. Connectionism is founded upon a neural metaphor in that connectionist networks are made up of many simple, neuron-like units. It is possible to lesion these networks and explore the effects of that damage. It is widely held that damaging connectionist networks informs our understanding of neuropsychology and cognitive psychology. To what extent then does it currently tell us, or is likely to tell us, anything about behavioral change following brain damage? Current connectionist models simulate either spontaneous recovery or the effects of retraining, and I discuss both approaches. Which is taken at present partly depends upon the connectionist framework used as the starting point. Most simulation work involving back-propagation has focused upon retraining lesioned networks, while work involving interactive activation has focused upon making inferences about the time course of spontaneous recovery. I discuss research in modeling deep dyslexia, aphasia, and dementia. I argue that further research on modeling spontaneous recovery is limited by the fixed architecture of most current connectionist networks.

Brain Damage, Chronic↗

PubMed1997

Constructing probabilistic models.

Bayesian networks have become one of the most popular probabilistic techniques in AI, largely due to the development of several efficient inference algorithms. In this paper we describe a heuristic method for constructing Bayesian networks. Our construction method relies on the relationship between Bayesian networks and decomposable models, a special kind of graphical model. We explain this relationship and then show how it can be used to facilitate model construction. Finally, we describe an implemented computer program that illustrates these ideas.

Algorithms↗

PubMed2005

Inferring gene regulatory relationships by combining target-target pattern recognition and regulator-specific motif examination.

Although microarray data have been successfully used for gene clustering and classification, the use of time series microarray data for constructing gene regulatory networks remains a particularly difficult task. The challenge lies in reliably inferring regulatory relationships from datasets that normally possess a large number of genes and a limited number of time points. In addition to the numerical challenge, the enormous complexity and dynamic properties of gene expression regulation also impede the progress of inferring gene regulatory relationships. Based on the accepted model of the relationship between regulator and target genes, we developed a new approach for inferring gene regulatory relationships by combining target-target pattern recognition and examination of regulator-specific binding sites in the promoter regions of putative target genes. Pattern recognition was accomplished in two steps: A first algorithm was used to search for the genes that share expression profile similarities with known target genes (KTGs) of each investigated regulator. The selected genes were further filtered by examining for the presence of regulator-specific binding sites in their promoter regions. As we implemented our approach to 18 yeast regulator genes and their known target genes, we discovered 267 new regulatory relationships, among which 15% are rediscovered, experimentally validated ones. Of the discovered target genes, 36.1% have the same or similar functions to a KTG of the regulator. An even larger number of inferred genes fall in the biological context and regulatory scope of their regulators. Since the regulatory relationships are inferred from pattern recognition between target-target genes, the method we present is especially suitable for inferring gene regulatory relationships in which there is a time delay between the expression of regulating and target genes.

Algorithms↗