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At least 1,099 records · Page 61Linked to original sources
PubMed2005

Differential network expression during drug and stress response.

MOTIVATION: The application of microarray chip technology has led to an explosion of data concerning the expression levels of the genes in an organism under a plethora of conditions. One of the major challenges of systems biology today is to devise generally applicable methods of interpreting this data in a way that will shed light on the complex relationships between multiple genes and their products. The importance of such information is clear, not only as an aid to areas of research like drug design, but also as a contribution to our understanding of the mechanisms behind an organism's ability to react to its environment. RESULTS: We detail one computational approach for using gene expression data to identify response networks in an organism. The method is based on the construction of biological networks given different sets of interaction information and the reduction of the said networks to important response sub-networks via the integration of the gene expression data. As an application, the expression data of known stress responders and DNA repair genes in Mycobacterium tuberculosis is used to construct a generic stress response sub-network. This is compared to similar networks constructed from data obtained from subjecting M.tuberculosis to various drugs; we are thus able to distinguish between generic stress response and specific drug response. We anticipate that this approach will be able to accelerate target identification and drug development for tuberculosis in the future. CONTACT: chris@lanl.gov SUPPLEMENTARY INFORMATION: Supplementary Figures 1 through 6 on drug response networks and differential network analyses on cerulenin, chlorpromazine, ethionamide, ofloxacin, thiolactomycin and triclosan. Supplementary Tables 1 to 3 on predicted protein interactions. http://www.santafe.edu/~chris/DifferentialNW.

Bacterial Proteins↗
PubMed2006

Integrating multi-attribute similarity networks for robust representation of the protein space.

MOTIVATION: A global view of the protein space is essential for functional and evolutionary analysis of proteins. In order to achieve this, a similarity network can be built using pairwise relationships among proteins. However, existing similarity networks employ a single similarity measure and therefore their utility depends highly on the quality of the selected measure. A more robust representation of the protein space can be realized if multiple sources of information are used. RESULTS: We propose a novel approach for analyzing multi-attribute similarity networks by combining random walks on graphs with Bayesian theory. A multi-attribute network is created by combining sequence and structure based similarity measures. For each attribute of the similarity network, one can compute a measure of affinity from a given protein to every other protein in the network using random walks. This process makes use of the implicit clustering information of the similarity network, and we show that it is superior to naive, local ranking methods. We then combine the computed affinities using a Bayesian framework. In particular, when we train a Bayesian model for automated classification of a novel protein, we achieve high classification accuracy and outperform single attribute networks. In addition, we demonstrate the effectiveness of our technique by comparison with a competing kernel-based information integration approach.

Algorithms↗
PubMed2006

Inferring gene regulatory networks from time series data using the minimum description length principle.

MOTIVATION: A central question in reverse engineering of genetic networks consists in determining the dependencies and regulating relationships among genes. This paper addresses the problem of inferring genetic regulatory networks from time-series gene-expression profiles. By adopting a probabilistic modeling framework compatible with the family of models represented by dynamic Bayesian networks and probabilistic Boolean networks, this paper proposes a network inference algorithm to recover not only the direct gene connectivity but also the regulating orientations. RESULTS: Based on the minimum description length principle, a novel network inference algorithm is proposed that greatly shrinks the search space for graphical solutions and achieves a good trade-off between modeling complexity and data fitting. Simulation results show that the algorithm achieves good performance in the case of synthetic networks. Compared with existing state-of-the-art results in the literature, the proposed algorithm exceptionally excels in efficiency, accuracy, robustness and scalability. Given a time-series dataset for Drosophila melanogaster, the paper proposes a genetic regulatory network involved in Drosophila's muscle development. AVAILABILITY: Available from the authors upon request.

Algorithms↗
PubMed2006

The tYNA platform for comparative interactomics: a web tool for managing, comparing and mining multiple networks.

UNLABELLED: Biological processes involve complex networks of interactions between molecules. Various large-scale experiments and curation efforts have led to preliminary versions of complete cellular networks for a number of organisms. To grapple with these networks, we developed TopNet-like Yale Network Analyzer (tYNA), a Web system for managing, comparing and mining multiple networks, both directed and undirected. tYNA efficiently implements methods that have proven useful in network analysis, including identifying defective cliques, finding small network motifs (such as feed-forward loops), calculating global statistics (such as the clustering coefficient and eccentricity), and identifying hubs and bottlenecks. It also allows one to manage a large number of private and public networks using a flexible tagging system, to filter them based on a variety of criteria, and to visualize them through an interactive graphical interface. A number of commonly used biological datasets have been pre-loaded into tYNA, standardized and grouped into different categories. AVAILABILITY: The tYNA system can be accessed at http://networks.gersteinlab.org/tyna. The source code, JavaDoc API and WSDL can also be downloaded from the website. tYNA can also be accessed from the Cytoscape software using a plugin.

Computer Graphics↗
PubMed2007

Small-world anatomical networks in the human brain revealed by cortical thickness from MRI.

An important issue in neuroscience is the characterization for the underlying architectures of complex brain networks. However, little is known about the network of anatomical connections in the human brain. Here, we investigated large-scale anatomical connection patterns of the human cerebral cortex using cortical thickness measurements from magnetic resonance images. Two areas were considered anatomically connected if they showed statistically significant correlations in cortical thickness and we constructed the network of such connections using 124 brains from the International Consortium for Brain Mapping database. Significant short- and long-range connections were found in both intra- and interhemispheric regions, many of which were consistent with known neuroanatomical pathways measured by human diffusion imaging. More importantly, we showed that the human brain anatomical network had robust small-world properties with cohesive neighborhoods and short mean distances between regions that were insensitive to the selection of correlation thresholds. Additionally, we also found that this network and the probability of finding a connection between 2 regions for a given anatomical distance had both exponentially truncated power-law distributions. Our results demonstrated the basic organizational principles for the anatomical network in the human brain compatible with previous functional networks studies, which provides important implications of how functional brain states originate from their structural underpinnings. To our knowledge, this study provides the first report of small-world properties and degree distribution of anatomical networks in the human brain using cortical thickness measurements.

Brain↗
PubMed2006

European primary care surveillance networks: their structure and operation.

BACKGROUND: In many European countries, primary care surveillance networks play a role in public health surveillance. OBJECTIVES: To update an inventory of surveillance networks, to describe them and to report on their organization and function in a standardized way. To investigate whether and under what conditions their information can contribute to surveillance at a European level. METHODS: Surveillance networks were defined as 'A network of practices or community based primary care physicians who monitor one or more specific illness problems on a regular and continuing basis'. For the inventory questionnaires were sent out, followed by site visits to seven networks using a standardized audit checklist. RESULTS: We sent out 75 questionnaires and received 57 back (73% response rate), with 33 (58% of responders) fitting our selection criteria. National surveillance networks were identified in 11 countries. Many had an infectious disease surveillance component, particularly for influenza. Most were funded by the Ministry of Health, some by research funds. The median number of general practitioners was 120, comprising a stable group of general practitioners and covering a representative sample of the general population. The frequency of reporting varied from daily to annually, depending on the purpose of the network. CONCLUSIONS: A large number of primary care surveillance networks exist in Europe. Their value has been shown with the surveillance of influenza, but the challenge is now to extend their use to other diseases. When fulfilling identical minimal criteria they can provide comparable estimates of morbidity, ultimately leading to improved national and European surveillance.

Europe↗
PubMed1999

Social networks and disability transitions across eight intervals of yearly data in the New Haven EPESE.

OBJECTIVES: There is considerable evidence that social networks are strongly related to survival and other health outcomes. However, findings regarding the effect of social networks on disability outcomes have been inconsistent. This study examines this relationship with respect to the risk of developing disability and recovering from disability. METHODS: Data come from a community-based sample of the New Haven population aged 65 years and older, with nine annual interviews conducted between 1982 and 1991. Disability was measured by a 6-item index of activities of daily living (ADL), and a 3-item Rosow-Breslau index, with disability defined as impairment in one or more tasks on each measure. Social network variables were constructed for each of four domains of ties: children, relatives, friends, and a confidant, and a summary measure of total social networks. A Markov model was used to estimate one-year disability transitions averaged across all 8 intervals, after controlling for sociodemographic and health-related variables. RESULTS: Total social networks was associated with a significantly reduced risk of developing ADL disability (beta = -0.009, p < .01), and a significantly increased likelihood of ADL recovery (beta = 0.017, p < .01). Emotional and instrumental support did not affect the protective effect of social networks against disability, but partially accounted for their effect on enhanced recovery. Network variables related to relatives and friends were significantly associated with disability and recovery risks, but those related to children or a confidant were not. The associations with disability transitions as measured by the Rosow-Breslau index were generally smaller and nonsignificant. DISCUSSION: The findings lend further support for the role of social relationships in important health outcomes in old age. They suggest that being "embedded" in a social network of relatives and friends reduces risk for ADL disability, and enhances recovery from ADL disability.

Activities of Daily Living↗
PubMed2004

PathBLAST: a tool for alignment of protein interaction networks.

PathBLAST is a network alignment and search tool for comparing protein interaction networks across species to identify protein pathways and complexes that have been conserved by evolution. The basic method searches for high-scoring alignments between pairs of protein interaction paths, for which proteins of the first path are paired with putative orthologs occurring in the same order in the second path. This technique discriminates between true- and false-positive interactions and allows for functional annotation of protein interaction pathways based on similarity to the network of another, well-characterized species. PathBLAST is now available at http://www.pathblast.org/ as a web-based query. In this implementation, the user specifies a short protein interaction path for query against a target protein-protein interaction network selected from a network database. PathBLAST returns a ranked list of matching paths from the target network along with a graphical view of these paths and the overlap among them. Target protein-protein interaction networks are currently available for Helicobacter pylori, Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. Just as BLAST enables rapid comparison of protein sequences between genomes, tools such as PathBLAST are enabling comparative genomics at the network level.

Animals↗
PubMed1997

Relation of social network characteristics to 5-year mortality among young-old versus old-old white women in an urban community.

This study examines age-related differences in the association between social network characteristics and mortality for aged white women. Subjects include a community-dwelling sample of white women aged > or = 65 years (n = 806), who lived in northeast Baltimore, Maryland, in 1984. Three characteristics of social networks were measured: availability of network resources; contact with network resources; and integration into the neighborhood. The association of social network with 5-year mortality was examined with a proportional hazards model adjusting for perceived health status, impairment in physical activities of daily living, number of chronic conditions, and years of education. Analyses were stratified by age (65-74 years, > or = 75 years). Elements of social network contact and neighborhood integration were associated with reduced mortality among women aged > or = 75 years, but not among women aged 65-74 years. In the > or = 75 years group, women who had no contact with children, friends, and group organizations showed hazard ratios (95% confidence intervals (CI)) of 3.1 (1.2-7.5), 2.2 (1.0-4.9), and 2.8 (1.2-6.5), respectively. Women who had lived < or = 10 years in the neighborhood and women who had no interaction with local merchants showed hazard ratios of 2.5 (95% CI 1.3-4.8) and 2.2 (95% CI 1.2-3.9), respectively. Thus, both age and specific aspects of network structure were found to influence the association between social networks and mortality in elderly women.

Aged↗
PubMed1981

Analysis of a schizophrenic psychosocial network.

The amorphous concept of social support systems merits construction of a conceptually coherent theoretical model linked to social theory and amenable to empirical investigation. The social network paradigm is presented as such a model. The model is further defined in terms of the intimate psychosocial network, which has been empirically studied with the Pattison Psychosocial Kinship Inventory. The characteristics of the normal network are shown to differ substantially in the schizophrenic network. The structure and functions of the schizophrenic network are illustrated in a case study analysis. The schizophrenic network is shown to exhibit dynamics that generate and perpetuate psychotic behavior. A strategy for network intervention is described, based on the model of structural change in the network social system.

Adult↗
PubMed1981

Schizophrenia: a network crisis.

The results of a study comparing the structure and function of the social networks of a group of first-admission schizophrenics with those of a group of multiple-admission schizophrenics are presented. Structurally, the networks of the first-admission patients are larger and more interconnected. Functionally, their networks have a greater percentage of multiplex and nondependent links. On the basis of these data, it is concluded that the most dramatic changes in social networks develop after the patient's first hospitalization. The dissolution of the patient's network is attributed to the antagonistic attitudes and reactions of those close to the patient, as well as to the patient's impaired social competence. Schizophrenia seemingly is a network crisis not only for the individual but for the network as a whole. It is suggested that active intervention at the time of the first psychotic episode may be helpful in avoiding network collapse and the patient's resultant social isolation.

Adolescent↗
PubMed1998

Social network dynamics and HIV transmission.

OBJECTIVE: To prospectively study changes in the social networks of persons at presumably high risk for HIV in a community with low prevalence and little endogenous transmission. METHODS: From a cohort of 595 persons at high risk (prostitutes, injecting drug users, and sexual partners of these persons) and nearly 6000 identified contacts, we examined the social networks of a subset of 96 persons who were interviewed once per year for 3 years. We assessed their network configuration, network stability, and changes in risk configuration and risk behavior using epidemiologic and social network analysis, and visualization techniques. RESULTS: Some significant decrease in personal risk-taking was documented during the course of the study, particularly with regard to needle-sharing. The size and number of connected components (groups that are completely connected) declined. Microstructures (small subgroups of persons that interact intensely) were either not present, or declined appreciably during the period of observation. CONCLUSIONS: In this area of low prevalence, the lack of endogenous transmission of HIV may be related in part to the lack of a network structure that fosters active propagation, despite the continued presence of risky behaviors. Although the relative contribution of network structure and personal behavior cannot be ascertained from these data, the study suggests an important role for network configuration in the transmission dynamics of HIV.

Cohort Studies↗
PubMed2000

Hospital networking. Comparing the work of nurses with flexible and traditional schedules.

OBJECTIVE: This research study was conducted to contrast workplace socialization of nurses working flexible (flex) and traditional schedules in an acute care setting. The study illustrates the types of social networks used by both types of nurses in a reengineered healthcare environment. SUMMARY BACKGROUND DATA: Reengineering strategies, such as flex nurse staffing, add a new dimension to workplace change and adaptation. Few studies have examined the similarities and differences between nurses working flex and traditional schedules. The research literature shows that workplace socialization significantly affects job satisfaction, organizational commitment, and retention. No studies have examined how the process of socialization--forming social networks--differs for nurses working traditional or flex schedules. METHODS AND SUBJECTS: A convenience sample of 120 nurses working traditional schedules and 46 nurses working flex schedules from a pediatric, tertiary care setting completed the Social Network Questionnaire (SNQ), a standardized instrument that records individuals' social network composition and function. RESULTS: No significant differences were found in the nurses' social network composition. Both types of nurses constructed peer-based networks and nurse managers were also present in their networks. Nurses working traditional schedules used significantly more peer members for different types of emotional support, such as reassurance and handling emotional upsets. CONCLUSIONS: Workplace networks are important to both types of nurses. Nurses on flex schedules may form less social attachments in order to manage the increased demands of moving among multiple units. This group of nurses can provide clues for adaptive change in reengineered environments.

Female↗
PubMed1995

Predicting agency participation in interorganizational networks providing community care.

In response to health care reform, health care providers have begun to develop interorganizational networks. At present, however, relatively little is known about factors facilitating participation in networks. To this end, organizational characteristics and views were obtained from key informants from both "Lead" and "Affiliate" Agencies participating in the networks for the Living-at-Home Program (LAHP) Demonstration (N = 131) using an Organizational Change Survey. Logistic regression analysis was used to examine factors related to network member agencies' participation. Significant relationships were found between decreased participation and lack of agreement between network agencies regarding expectations (P = 0.02), membership in a network with a Medical Lead Agency (P < 0.01), and Lead Agency inexperience (P < 0.01). Agencies with lower ratings of the impact that LAHP had on their community were more likely to decrease their participation (P = 0.01). The number of unoccupied nursing home beds in the community was positively and significantly related to decreased participation (P < 0.001). These results suggest that leadership skills of the Lead Agency, and in particular, experience, may be among the chief requirements for the creation and development of successful networks, and confirm that inexperienced Lead Agencies may face an uphill battle in terms of recruiting and maintaining network members.

California↗
PubMed2000

Social network methods for endemic foci of syphilis: a pilot project.

BACKGROUND: Social network methods have improved our understanding of sexually transmitted disease transmission dynamics, and may be of use in routine field operations for partner notification. GOAL: To augment traditional syphilis-control activities with social network methods in an Atlanta area with high syphilis morbidity. STUDY DESIGN: Disease investigators conducted interviews, used network diagrams to prioritize their work, and relied on network connections for finding hard-to-reach persons. RESULTS: A total of 396 contacts were elicited from 48 infected and 50 uninfected persons. The cumulative prevalence of syphilis was 12.6%, and 24 persons infected with HIV were identified. Network methods disclosed a large, interconnected group (276 persons) characterized by high network centrality and the substantial presence of small, interactive subgroups (microstructures). CONCLUSION: The network approach is a feasible field technique, and can identify core groups involved in the intense transmission of syphilis. The targeted, network-based approach may be useful in attempts to eliminate syphilis.

Adult↗
PubMed2005

The elastic fiber network of the anulus fibrosus of the normal and scoliotic human intervertebral disc.

STUDY DESIGN: Immunohistochemical study of elastic fibers in human intervertebral discs (IVD) collected at surgery from patients with scoliosis. OBJECTIVES: To compare the elastic fiber network in scoliotic discs (idiopathic scoliosis or neuromuscular scoliosis) to that of control (normal) discs. To study whether the change in elastic fiber organization could contribute to the progression of spinal deformity. SUMMARY OF BACKGROUND DATA: Elastin and elastic fibers have been identified previously in human IVD but were believed to contribute little to the tissue's mechanical properties. However, a recent immunohistochemical study has revealed an abundant and organized elastic fiber network in bovine IVD, indicating that elastic fibers could play an important mechanical role. This article reports the organization of elastic fibers in human IVD and the changes of elastic fiber organization in scoliosis. METHODS: Intact wedges of IVD were obtained from patients undergoing surgery for scoliosis (aged 12-22 years). Control discs were obtained from a patient (aged 12 years) with a spinal tumor and a trauma patient (aged 17 years). The discs were dissected to give radial slices and were snap frozen. Frozen sections were cut and digested with hyaluronidase to remove glycosaminoglycans. Micrographs of the sections were examined by polarized light to visualize collagen organization. The elastic fiber network was visualized immunohistochemically or by histochemical staining with orcein. RESULTS: A highly organized elastic fiber network, similar to that described in bovine discs, was revealed in the control human discs. In the anulus fibrosus of control discs, dense elastic fibers were located between adjacent lamellae, with fibers also present within individual lamellae. Elastic fibers appeared to be long (>200 microm) and straight in outer anulus, whereas in inner anulus, they nearly ran parallel to each other and at an angle of approximately 60 degrees or 120 degrees to those in adjacent lamellae. However, in scoliotic discs, elastic fibers were sparse, and the collagen and elastic fiber networks were disorganized with loss of lamellar structure. Cell clusters, one of typical degenerative feature, were seen in scoliotic discs but not in age-matched control discs. CONCLUSIONS: Our results reveal an abundant and organized network of elastic fibers in the adolescent (12 and 17-year-olds) human IVD, and suggest that elastic fiber network plays a significant biomechanical role. This network is sparse and disrupted in scoliotic discs, and could be involved in the progression of the spinal deformity.

Adolescent↗
PubMed2006

Spatially resolved non-invasive chemical stimulation for modulation of signalling in reconstructed neuronal networks.

Functional coupling of reconstructed neuronal networks with microelectronic circuits has potential for the development of bioelectronic devices, pharmacological assays and medical engineering. Modulation of the signal processing properties of on-chip reconstructed neuronal networks is an important aspect in such applications. It may be achieved by controlling the biochemical environment, preferably with cellular resolution. In this work, we attempt to design cell-cell and cell-medium interactions in confined geometries with the aim to manipulate non-invasively the activity pattern of an individual neuron in neuronal networks for long-term modulation. Therefore, we have developed a biohybrid system in which neuronal networks are reconstructed on microstructured silicon chips and interfaced to a microfluidic system. A high degree of geometrical control over the network architecture and alignment of the network with the substrate features has been achieved by means of aligned microcontact printing. Localized non-invasive on-chip chemical stimulation of micropatterned rat cortical neurons within a network has been demonstrated with an excitatory neurotransmitter glutamate. Our system will be useful for the investigation of the influence of localized chemical gradients on network formation and long-term modulation.

Animals↗
PubMed2006

Network frailty and the geometry of herd immunity.

The spread of infectious disease through communities depends fundamentally on the underlying patterns of contacts between individuals. Generally, the more contacts one individual has, the more vulnerable they are to infection during an epidemic. Thus, outbreaks disproportionately impact the most highly connected demographics. Epidemics can then lead, through immunization or removal of individuals, to sparser networks that are more resistant to future transmission of a given disease. Using several classes of contact networks-Poisson, scale-free and small-world-we characterize the structural evolution of a network due to an epidemic in terms of frailty (the degree to which highly connected individuals are more vulnerable to infection) and interference (the extent to which the epidemic cuts off connectivity among the susceptible population that remains following an epidemic). The evolution of the susceptible network over the course of an epidemic differs among the classes of networks; frailty, relative to interference, accounts for an increasing component of network evolution on networks with greater variance in contacts. The result is that immunization due to prior epidemics can provide greater community protection than random vaccination on networks with heterogeneous contact patterns, while the reverse is true for highly structured populations.

Animal Diseases↗