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Network capacity analysis for latent attractor computation.

Attractor networks have been one of the most successful paradigms in neural computation, and have been used as models of computation in the nervous system. Recently, we proposed a paradigm called 'latent attractors' where attractors embedded in a recurrent network via Hebbian learning are used to channel network response to external input rather than becoming manifest themselves. This allows the network to generate context-sensitive internal codes in complex situations. Latent attractors are particularly helpful in explaining computations within the hippocampus--a brain region of fundamental significance for memory and spatial learning. Latent attractor networks are a special case of associative memory networks. The model studied here consists of a two-layer recurrent network with attractors stored in the recurrent connections using a clipped Hebbian learning rule. The firing in both layers is competitive--K winners take all firing. The number of neurons allowed to fire, K, is smaller than the size of the active set of the stored attractors. The performance of latent attractor networks depends on the number of such attractors that a network can sustain. In this paper, we use signal-to-noise methods developed for standard associative memory networks to do a theoretical and computational analysis of the capacity and dynamics of latent attractor networks. This is an important first step in making latent attractors a viable tool in the repertoire of neural computation. The method developed here leads to numerical estimates of capacity limits and dynamics of latent attractor networks. The technique represents a general approach to analyse standard associative memory networks with competitive firing. The theoretical analysis is based on estimates of the dendritic sum distributions using Gaussian approximation. Because of the competitive firing property, the capacity results are estimated only numerically by iteratively computing the probability of erroneous firings. The analysis contains two cases: the simple case analysis which accounts for the correlations between weights due to shared patterns and the detailed case analysis which includes also the temporal correlations between the network's present and previous state. The latter case predicts better the dynamics of the network state for non-zero initial spurious firing. The theoretical analysis also shows the influence of the main parameters of the model on the storage capacity.

Animals↗

Information infrastructure for inter-organizational mental health services: an actor network theory analysis of psychiatric rehabilitation.

In the supply of mental health services to communities, data and information are managed not only by clinical organizations, but also by welfare state agencies and charities. The aim of this study is to use methods of analysis from actor network theory to identify organizational interventions necessary for the development of an information infrastructure for inter-organizational mental health services. Data was collected in a project aimed at developing an information system that supports inter-organizational psychiatric rehabilitation in a Swedish municipality. Three organizational interventions were identified: an integrated service policy defined by the national government, a common legal framework allowing sharing of high-level client data, and commissioned support for local inter-agency workspaces. It is concluded that organizational interventions must be regarded when configuring an information infrastructure for mental health services. Organizational interventions should also routinely be addressed in systems design methods to be used in inter-organizational settings.

Interinstitutional Relations↗

Uncertainty in the output of artificial neural networks.

Analysis of the performance of artificial neural networks (ANNs) is usually based on aggregate results on a population of cases. In this paper, we analyze ANN output corresponding to the individual case. We show variability in the outputs of multiple ANNs that are trained and "optimized" from a common set of training cases. We predict this variability from a theoretical standpoint on the basis that multiple ANNs can be optimized to achieve similar overall performance on a population of cases, but produce different outputs for the same individual case because the ANNs use different weights. We use simulations to show that the average standard deviation in the ANN output can be two orders of magnitude higher than the standard deviation in the ANN overall performance measured by the Az value. We further show this variability using an example in mammography where the ANNs are used to classify clustered microcalcifications as malignant or benign based on image features extracted from mammograms. This variability in the ANN output is generally not recognized because a trained individual ANN becomes a deterministic model. Recognition of this variability and the deterministic view of the ANN present a fundamental contradiction. The implication of this variability to the classification task warrants additional study.

Algorithms↗

Hierarchical neural networks for survival analysis.

Neural networks offer the potential of providing more accurate predictions of survival time than do traditional methods. Their use in medical applications has, however, been limited, especially when some data is censored or the frequency of events is low. To reduce the effect of these problems, we have developed a hierarchical architecture of neural networks that predicts survival in a stepwise manner. Predictions are made for the first time interval, then for the second, and so on. The system produces a survival estimate for patients at each interval, given relevant covariates, and is able to handle continuous and discrete variables, as well as censored data. We compared the hierarchical system of neural networks with a nonhierarchical system for a data set of 428 AIDS patients. The hierarchical model predicted survival more accurately than did the nonhierarchical (although both had low sensitivity). The hierarchical model could also learn the same patterns in less than half the time required by the nonhierarchical model. These results suggest that the use of hierarchical systems is advantageous when censored data is present, the number of events is small, and time-dependent variables are necessary.

Acquired Immunodeficiency Syndrome↗

A generalized framework for network component analysis.

The authors recently introduced a framework, named Network Component Analysis (NCA), for the reconstruction of the dynamics of transcriptional regulators' activities from gene expression assays. The original formulation had certain shortcomings that limited NCA's application to a wide class of network dynamics reconstruction problems, either because of limitations in the sample size or because of the stringent requirements imposed by the set of identifiability conditions. In addition, the performance characteristics of the method for various levels of data noise or in the presence of model inaccuracies were never investigated. In this article, the following aspects of NCA have been addressed, resulting in a set of extensions to the original framework: 1) The sufficient conditions on the a priori connectivity information (required for successful reconstructions via NCA) are made less stringent, allowing easier verification of whether a network topology is identifiable, as well as extending the class of identifiable systems. Such a result is accomplished by introducing a set of identifiability requirements that can be directly tested on the regulatory architecture, rather than on specific instances of the system matrix. 2) The two-stage least square iterative procedure used in NCA is proven to identify stationary points of the likelihood function, under Gaussian noise assumption, thus reinforcing the statistical foundations of the method. 3) A framework for the simultaneous reconstruction of multiple regulatory subnetworks is introduced, thus overcoming one of the critical limitations of the original formulation of the decomposition, for example, occurring for poorly sampled data (typical of microarray experiments). A set of monte carlo simulations we conducted with synthetic data suggests that the approach is indeed capable of accurately reconstructing regulatory signals when these are the input of large-scale networks that satisfy the suggested identifiability criteria, even under fairly noisy conditions. The sensitivity of the reconstructed signals to inaccuracies in the hypothesized network topology is also investigated. We demonstrate the feasibility of our approach for the simultaneous reconstruction of multiple regulatory subnetworks from the same data set with a successful application of the technique to gene expression measurements of the bacterium Escherichia coli.

Algorithms↗

Genomic analysis of essentiality within protein networks.

In this article, we introduce the notion of 'marginal essentiality' through combining quantitatively the results from large-scale phenotypic experiments (e.g. growth rate inhibition from knockouts). We find that this quantity relates to many of the topological characteristics of protein-protein interaction networks. In particular, proteins with a greater degree of marginal essentiality tend to be network hubs (i.e. with many interactions) and tend to have a shorter characteristic path length to their neighbors. We extend our network analysis to encompass transcriptional regulatory networks. Although transcription factors with many targets tend to be essential, surprisingly, we find that genes that are regulated by many transcription factors are usually not essential.

Animals↗

Scale-free user-network approach to telephone network traffic analysis.

The effect of the user network on the telephone network traffic is studied in this paper. Unlike classical traffic analysis, where users are assumed to be connected uniformly, our proposed method employs a scale-free network to model the behavior of telephone users. Each user has a fixed set of acquaintances with whom the user may communicate, and the number of acquaintances follows a power-law distribution. We show that compared to conventional analysis based upon a fully connected user network, the network traffic is significantly different when the user network assumes a scale-free property. Specifically, network blocking (call failure) is generally more severe in the case of a scale-free user network. It is also shown that the carried traffic is practically limited by the scale-free property of the user network, rather than by the network capacity.

Journal Article↗

Packet traffic analysis of scale-free networks for large-scale network-on-chip design.

Recent progress in integrated circuit technologies requires precise evaluation between dynamic characteristics and topological architecture design. In this paper, we have investigated the performance evaluation of network-on-chip (NoC) architectures constructed with diverse scale-free network topologies by dynamic packet traffic simulation and theoretical network analysis. Topological differences of scale-free networks are evaluated by the degree-degree correlations that indicate topological tendency between the degree of a node and that of the nearest neighbors. Our simulation results quantitatively show that the NoC architecture constructed with the topology where hubs mostly connect to lower-degree nodes is found to achieve short latency and low packet loss ratio since it can disperse traffic load and avoid the extreme concentration of load on hubs.

Journal Article↗

Visual analysis of large heterogeneous social networks by semantic and structural abstraction.

Social network analysis is an active area of study beyond sociology. It uncovers the invisible relationships between actors in a network and provides understanding of social processes and behaviors. It has become an important technique in a variety of application areas such as the Web, organizational studies, and homeland security. This paper presents a visual analytics tool, OntoVis, for understanding large, heterogeneous social networks, in which nodes and links could represent different concepts and relations, respectively. These concepts and relations are related through an ontology (also known as a schema). OntoVis is named such because it uses information in the ontology associated with a social network to semantically prune a large, heterogeneous network. In addition to semantic abstraction, OntoVis also allows users to do structural abstraction and importance filtering to make large networks manageable and to facilitate analytic reasoning. All these unique capabilities of OntoVis are illustrated with several case studies.

Algorithms↗

Diagnostic accuracy of pancreatic enzymes evaluated by use of multivariate data analysis.

We analyzed pancreatic enzyme data from 508 patients with suspected pancreatitis by neural network analysis, by an Expert multirule generation protocol, and by receiver-operator characteristic (ROC) curve analysis of a single test result. Neural network analysis showed that use of lipase provided the best means for diagnosing pancreatitis. Diagnostic accuracies achieved by using amylase only, lipase only, and amylase and lipase in combination were 76%, 82%, and 84%, respectively. Use of the Expert rule generation protocol provided a diagnostic accuracy of 92% when rules for single and multiple samplings were combined. ROC curve analysis for initial enzyme activities showed the maximal diagnostic accuracy to be 82% and 85% for amylase and lipase, respectively; use of peak enzyme activities yielded accuracies of 81% and 88%, respectively. The evaluation of laboratory test data should include analysis of the diagnostic accuracy of laboratory tests by multivariate techniques such as neural network analysis or an Expert systems approach. Multivariate analysis should allow for a more realistic assessment of the diagnosis accuracy of laboratory tests because all the available data are included in the evaluation.

Amylases↗

Wellness lifestyles II: Modeling the dynamic of wellness, health lifestyle practices, and Network Spinal Analysis.

OBJECTIVE: Empirical application of a theoretical framework linking use of Network Spinal Analysis (NSA; a holistic, wellness-oriented form of complementary and alternative medicine [CAM]), health lifestyle practices, and self-reported health and wellness. DESIGN: Cross-sectional self-administered survey study. RESPONDENTS: Two thousand five hundred and ninety-six (2596) patients from 156 offices of doctors who were members of the Association for Network Chiropractic (currently titled Association for Network Care); estimated response rate was 69%. MEASURES: Exogenous variables entered into the structural equation model include gender, age, education, income, marital status, ailments, life change, and trauma. A wellness construct consisted of calculated difference scores between two referents, "presently" and "before Network" care, for self-reported items representing wellness domains of physical state, mental-emotional state, stress evaluation, and life enjoyment. Positive reported change in nine items assembled into dietary practices, health practices, and health risk dimensions serve as indicators of the construct of changes in health lifestyle practices. The NSA care construct consisted of duration of care in months, awareness of energy and awareness of breathing since beginning Network care. RESULTS: Of the exogenous variables only gender, age, and education remain in the final parsimonious structural equation model in these data. Reported wellness benefits accrue to individuals along a direct path from both self-reported positive lifestyle change (0.22), and from NSA care (0.43). The path (0.65) from NSA care to positive health lifestyle changes indicates that NSA care also has an indirect effect on wellness through changes in health lifestyle practices. CONCLUSIONS: The Structural Equation model tested in these analyses lends support to our theoretical framework linking wellness, health lifestyles, and CAM. This study provides further evidence that our measurements of health and wellness are particularly appropriate for investigating wellness-oriented CAM. There is a positive relationship between the experience of NSA care and self-reported improvements in wellness as well as self-reported changes in lifestyle practices. NSA care users tend toward the practice of a positive health lifestyle, which also has a direct effect on reported improvements in wellness. These empirical links are discussed relative to the sociodemographic characteristics of this population and show that use of NSA care is an aspect of a wellness lifestyle.

Adult↗

A network-based analysis of the late-phase reaction of the skin.

BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. OBJECTIVE: We sought to identify disease-associated pathways in the LPR using a network-based analysis. METHODS: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from T(H)2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of T(H)2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4- dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.

Adult↗

Prediction of lower pole stone clearance after shock wave lithotripsy using an artificial neural network.

PURPOSE: We performed this study as a comprehensive evaluation of variables reported to affect lower pole stone clearance after shock wave lithotripsy using artificial neural network analysis. MATERIALS AND METHODS: The radiographic images and treatment records of 680 patients with lower pole renal calculi treated with primary shock wave lithotripsy using the Wolf Piezolith 2500 (Wolf, Knittlingen, Germany) lithotriptor were retrospectively evaluated by applying artificial neural network analysis. Successful stone clearance was defined as absent fragments of any size detected on plain x-ray with tomography and/or excretory pyelography performed 6 months after treatment. Prognostic variables included patient characteristics, laboratory values, stone characteristics and the spatial anatomy of the lower pole, as defined by infundibular length, diameter, caliceal pelvic height, 2 measurements of the lower infundibulopelvic and infundibuloureteropelvic angles as well as the pattern of dynamic urinary transport. RESULTS: Artificial neural network analysis had 92% accuracy for correctly predicting lower pole stone clearance. The pattern of dynamic urinary transport represented the most influential predictor of stone clearance, followed by a measure of the infundibuloureteropelvic angle, body mass index, caliceal pelvic height and stone size. Anatomical measurements of lower pole anatomy and classification of the type of urinary transport were well reproducible with low intra-observer and interobserver variability (correlation coefficient alpha >0.8). CONCLUSIONS: In a comprehensive analysis of variables reported to influence lower pole stone clearance artificial neural network analysis predicted stone clearance with a high degree of accuracy. The relative importance of dynamic urinary transport in lower pole stones and the usefulness of artificial neural network analysis to predict shock wave lithotripsy outcomes in individuals must be confirmed in a prospective trial.

Adolescent↗

Integrative analysis of the cancer transcriptome.

DNA microarrays have been widely applied to the study of human cancer, delineating myriad molecular subtypes of cancer, many of which are associated with distinct biological underpinnings, disease progression and treatment response. These primary analyses have begun to decipher the molecular heterogeneity of cancer, but integrative analyses that evaluate cancer transcriptome data in the context of other data sources are often capable of extracting deeper biological insight from the data. Here we discuss several such integrative computational and analytical approaches, including meta-analysis, functional enrichment analysis, interactome analysis, transcriptional network analysis and integrative model system analysis.

Animals↗

Noninvasive, continuous evaluation of peripheral vascular resistance in humans.

We sought a noninvasive alternative method of monitoring peripheral vascular resistance continuously in humans, based on the analysis of arterial pressure waveforms. Radial arterial pressure waveforms were recorded noninvasively with a tonometer and analysed using a neural network method. To test the accuracy of this method, the peripheral vascular resistance was also determined by an invasive thermodilution method using a Swan-Ganz catheter in 20 subjects. To test the method in a clinical application, peripheral vascular resistance was determined by the noninvasive method before and after administration of nifedipine in 6 patients with essential hypertension. Neural network analysis of waveforms reliably yielded values between 0.00 and 1.00. Peripheral vascular resistance determined by neural network analysis and according to the invasive method showed a significant (p< 0.005) positive linear correlation. The peripheral vascular resistance measured by neural network analysis showed a significant (p< 0.05) decrease 30 min after administration of nifedipine, paralleling a decrease in blood pressure. Neural network analysis of tonometric radial artery waveforms provides an accurate, noninvasive, and continuous index of peripheral vascular resistance in human subjects. This simple method should permit more extensive homodynamic studies and larger epidemiological surveys in contrast to those undertaken using invasive techniques.

Blood Pressure↗

Functional Analysis of MS-Based Proteomics Data: From Protein Groups to Networks.

Mass spectrometry-based proteomics allows the quantification of thousands of proteins, protein variants, and their modifications, in many biological samples. These are derived from the measurement of peptide relative quantities, and it is not always possible to distinguish proteins with similar sequences due to the absence of protein-specific peptides. In such cases, peptide signals are reported in protein groups that can correspond to several genes. Here, we show that multi-gene protein groups have a limited impact on GO-term enrichment, but selecting only one gene per group affects network analysis. We thus present the Cytoscape app Proteo Visualizer (https://apps.cytoscape.org/apps/ProteoVisualizer) that is designed for retrieving protein interaction networks from STRING using protein groups as input and thus allows visualization and network analysis of bottom-up MS-based proteomics data sets.

Proteomics↗

A study of electroencephalographic descriptors and end-tidal concentration in estimating depth of anesthesia.

OBJECTIVE: To study the usefulness of three electro-encephalographic descriptors, the average median frequency, the average 90% spectral edge frequency, and a bispectral variable were used with the anesthetic concentrations in estimating the depth of anesthesia. METHODS: Four channels of raw EEG data were collected from seven mongrel dogs in nine separate experiments under different levels of halothane anesthesia and nitrous oxide in oxygen. A tail clamp was used as the stimulus and the dog was labeled as a non-responder or responder based on its response. A bispectral variable of the EEG (just before a tail clamp) and the estimated MAC level of halothane and nitrous oxide combined were the two features used to characterize a single data point. A neural network analysis was done on 48 such data points. A second neural network analysis was done on 47 data points using average 90% spectral edge frequency and the estimated MAC level. The average median frequency of EEG was also evaluated, although a neural network analysis was not done. RESULTS: The first neural network needed nine weights in order to train and correctly classify all of the 12 points in the training set under a training tolerance of 0.2. It could correctly classify all of the remaining 36 data points as either belonging to responders or non-responders. A cross-validation procedure, which estimated the overall performance of the network against future data points, showed that the network misclassified two out of the 48 data points. The second neural network needed 25 weights in order to train and classify correctly all of the 26 points in the training set under a tolerance of 0.2. It was later able to classify all of the 21 points of the test group correctly. CONCLUSIONS: The bispectral variable seems to reduce the non-linearity in the boundary separating the class of non-responders from the class of responders. Consequently, the neural network based on the bispectral variable is less complex than the neural network that uses a power spectral variable as one of its inputs.

Anesthesia, Inhalation↗

Network-based analysis of metabolic regulation in the human red blood cell.

Reconstruction of cell-scale metabolic networks is now possible. A description of allowable metabolic network functions can be obtained using extreme pathways, which are the convex basis vectors of the solution space containing all steady state flux distributions. However, only a portion of these allowable network functions are physiologically possible due to kinetic and regulatory constraints. Methods are now needed that enable us to take a defined metabolic network and deduce candidate regulatory structures that control the selection of these physiologically relevant states. One such approach is the singular value decomposition (SVD) of extreme pathway matrices (P), which allows for the characterization of steady state solution spaces. Eigenpathways, which are the left singular vectors from the SVD of P, can be described and categorized by their biochemical function. SVD of P for the human red blood cell showed that the first five eigenpathways, out of a total of 23, effectively characterize all the relevant physiological states of red blood cell metabolism calculated with a detailed kinetic model. Thus, with five degrees of freedom the magnitude and nature of the regulatory needs are defined. Additionally, the dominant features of these first five eigenpathways described key metabolic splits that are indeed regulated in the human red blood cell. The extreme pathway matrix is derived directly from network topology and only knowledge of Vmax values is needed to reach these conclusions. Thus, we have implemented a network-based analysis of regulation that complements the study of individual regulatory events. This topological approach may provide candidate regulatory structures for metabolic networks with known stoichiometry but poorly characterized regulation.

Erythrocytes↗