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PubMed1998

Qualitative analysis of gene networks.

In this paper, we review the qualitative tools developed by our group for the analysis of regulatory networks. Focusing on the dynamical and biological roles of feedback circuits, this method can be applied in the context of both logical and differential formalisms. This approach already led to several interesting results about the relation between the network structure and the corresponding dynamical properties. In particular, it could be shown that at least one positive regulatory circuit is necessary to generate multistationarity (i.e., alternative states of gene expression), whereas at least one negative circuit is necessary to generate a stable oscillatory behavior. Applications to the analysis of complex gene networks, as well as to the synthesis of regulatory models to account for global expression data are discussed.

Animals↗
PubMed1999

Spatio-temporal analysis of electric brain activity during semantic and phonological word processing.

There is an ongoing debate in cognitive neuroscience about the time course and the functional independence of the different processes involved in encoding written language material. New data indicate very fast and highly parallel language analysis networks in the brain. Here we demonstrate a methodological approach to study the temporal dynamics of this network by searching for time periods where different task demands emphasize different aspects of the network. Multi-channel event related potentials (ERPs) were recorded during a semantic and a phonological reading task from 14 healthy subjects. Signals were analyzed exclusively on the basis of the spatial configuration of the electric potential distributions (ERP maps), since differences in these spatial patterns directly reflect changes in the configuration of the active sources in the brain. This analysis did not reveal any differences of the evoked brain electric fields between the two tasks up to 280 ms post-stimulus. The ERP maps then differed for a brief period between 280 and 380 ms, before they were similar again. The analysis of the maps using a global linear localization procedure revealed a network of areas, active in both tasks, that mainly involved the left postero-temporal and left antero-temporal regions. The left posterior activation was found already around 100 ms post-stimulus, indicating that language-specific functions appear early in time. We therefore conclude that phonological and semantic processing are essentially performed in both tasks and that only late decision-related processes influence the relative strength of activity of the different modules in the complex language network.

Adult↗
PubMed2006

Diagnosing benign and malignant lesions in breast tissue sections by using IR-microspectroscopy.

The collection of IR spectra through microscope optics and the visualization of the IR data by IR imaging represent a visualization approach, which uses infrared spectral features as a native intrinsic contrast mechanism. To illustrate the potential of this spectroscopic methodology in breast cancer research, we have acquired IR-microspectroscopic data from benign and malignant lesions in breast tissue sections by point microscopy with spot sizes of 30-40 microm. Four classes of distinct breast tissue spectra were defined and stored in the data base: fibroadenoma (a total of 1175 spectra from 14 patients), ductal carcinoma in situ (a total of 1349 spectra from 8 patients), connective tissue (a total of 464 spectra), and adipose tissue (a total of 146 spectra). Artifical neural network analysis, a supervised pattern recognition method, was used to develop an automated classifier to separate the four classes. After training the artifical neural network classifier, infrared spectra of independent external validation data sets ("unknown spectra") were analyzed. In this way, all spectra (a total of 386) taken from micro areas inside the epithelium of fibroadenomas from 4 patients were correctly classified. Out of the 421 spectra taken from micro areas of the in situ component of invasive ductal carcinomas of 3 patients, 93% were correctly identified. Based on these results, the potential of the IR-microspectroscopic approach for diagnosing breast tissue lesions is discussed.

Breast Neoplasms↗
PubMed2005

Epistasis analysis with global transcriptional phenotypes.

Classical epistasis analysis can determine the order of function of genes in pathways using morphological, biochemical and other phenotypes. It requires knowledge of the pathway's phenotypic output and a variety of experimental expertise and so is unsuitable for genome-scale analysis. Here we used microarray profiles of mutants as phenotypes for epistasis analysis. Considering genes that regulate activity of protein kinase A in Dictyostelium, we identified known and unknown epistatic relationships and reconstructed a genetic network with microarray phenotypes alone. This work shows that microarray data can provide a uniform, quantitative tool for large-scale genetic network analysis.

Animals↗
PubMed2007

Reduced genetic structure of north Ethiopian cattle revealed by Y-chromosome analysis.

Ethiopia is considered to be a putative migratory corridor for both Near-East Bos taurine and Arabian and Indian B. indicus cattle into East Africa. African pastoralism, which is associated with adaptation to specific habitats and farming systems, has contributed to the composite constitution of Ethiopian cattle. We analyse, for the first time, five Y-chromosome microsatellite markers from seven north Ethiopian cattle populations, using a European Holstein-Friesian population as a reference, to assess the paternal gene pool and to explore the mechanisms behind the genetic structure. Our results reveal that the indicine alleles predominate in the present populations, with only one animal in the Arado carrying the taurine alleles. The north Ethiopian cattle populations with one exception (Abergelle) are characterized by a general low Y-chromosome haplotype diversity, as well as by a reduced interpopulation variance (Phi(ST)=4.0%), which can be a result of strong male-mediated selective sweeps. Population structure revealed by multidimensional-scaling analysis differentiates two populations (Arado and Abergelle) from the rest. Analysis of molecular variance does not lend support to the traditional classification for the populations, which is mainly based on physical characteristics. A network analysis indicates two closely related founding haplotypes accounting for a large proportion (50.0% in Abergelle and 85.0-94.7% in others) of north Ethiopian cattle Y-chromosomes. Our findings point to a common, but limited, paternal origin of the north Ethiopian cattle populations and strong male-mediated gene flow among them. The findings also provide insight into the historical immigration of cattle into East Africa.

Animals↗
PubMed2006

Public health preparedness in Alberta: a systems-level study.

BACKGROUND: Recent international and national events have brought critical attention to the Canadian public health system and how prepared the system is to respond to various types of contemporary public health threats. This article describes the study design and methods being used to conduct a systems-level analysis of public health preparedness in the province of Alberta, Canada. The project is being funded under the Health Research Fund, Alberta Heritage Foundation for Medical Research. METHODS/DESIGN: We use an embedded, multiple-case study design, integrating qualitative and quantitative methods to measure empirically the degree of inter-organizational coordination existing among public health agencies in Alberta, Canada. We situate our measures of inter-organizational network ties within a systems-level framework to assess the relative influence of inter-organizational ties, individual organizational attributes, and institutional environmental features on public health preparedness. The relative contribution of each component is examined for two potential public health threats: pandemic influenza and West Nile virus. DISCUSSION: The organizational dimensions of public health preparedness depend on a complex mix of individual organizational characteristics, inter-agency relationships, and institutional environmental factors. Our study is designed to discriminate among these different system components and assess the independent influence of each on the other, as well as the overall level of public health preparedness in Alberta. While all agree that competent organizations and functioning networks are important components of public health preparedness, this study is one of the first to use formal network analysis to study the role of inter-agency networks in the development of prepared public health systems.

Alberta↗
PubMed2001

Phytoplankton group dynamics in the Bay of Marseilles during a 2-year survey based on analytical flow cytometry.

BACKGROUND: The Bay of Marseilles is under the influence of a large urban concentration and its maritime activities. All of them discharge compounds (hydrocarbons, excess nutrients, heavy metals, chemicals, etc.) that can alter the marine ecosystem. To investigate whether ultraphytoplankton (<10 microm) could be used as biosensors for their own ecosystem, a 2-year survey was conducted in the Bay of Marseilles. METHODS: Seven stations monitored water mass and potential anthropic effects in the bay. Seawater samples were collected monthly or bimonthly at three depths, prefiltered, fixed, and kept in liquid nitrogen until flow cytometric analysis. RESULTS: Five categories were created: Prochlorococcus, picoeukaryotes (<2 microm), nanoeukaryotes I (2--6 microm), nanoeukaryotes II (6--10 microm), and Synechococcus (<1.5 microm). Artificial neural network analysis (Kohonen self-organizing maps) produced the same number of clusters as cluster analysis with Winlist software (Verity Software House). CONCLUSIONS: In addition to the wide variabilities in abundance and biomass, there were a strong seasonal signal and sporadic events. Lessons are derived from this study for future monitoring of marine microorganisms.

Flow Cytometry↗
PubMed2003

Both processing speed and semantic memory organization predict verbal fluency in schizophrenia.

We systematically examined the relationship of both lexical retrieval and semantic memory organization to categorical verbal fluency performance in 40 outpatient schizophrenic subjects and 16 healthy controls. Mean choice reaction time (RT) on a lexical decision task was used as a measure of lexical retrieval efficiency. The complexity of semantic memory organization was measured using a Pathfinder semantic network analysis (calculated as the number of inter-node links obtained from a similarity rating task). In the schizophrenia group only, RT and semantic network links were each significantly negatively correlated with fluency and, together, accounted for 23% of the variance in fluency. RT and links were not significantly correlated with one another. Findings were unrelated to age, sex, education, or medication dose. Controlling for IQ reduced but did not abolish the relationship between fluency and network links. We conclude that the restricted verbal output of schizophrenic subjects is related both to impaired lexical retrieval and to variation in semantic memory organization, which partly reflects general intelligence. The statistical independence of the retrieval speed and organizational factors suggests that individuals with schizophrenia differ in the underlying processes that contribute to their reduced verbal fluency.

Adult↗
PubMed2003

Chlamydia trachomatis omp1 genotypic diversity and concordance with sexual network data.

Sexual and social network analysis have been proposed as novel sexually transmitted disease control and research tools. Here, the concordance between chlamydia genotype data and a large sexual network constructed from routinely collected contact tracing data was examined. A sexual network was constructed for Manitoba, Canada, from province-wide contact tracing data. Positive chlamydia specimens from the same time period were collected and genotyped by omp1 DNA sequencing. A high degree of concordance was found between transmission events, on the basis of molecular data, and proposed transmission events, on the basis of sexual network data. Discordant results appeared to occur when a portion of the network contained potential core group members or in areas where contact tracing is difficult to carry out. The agreement between the molecular and epidemiologic data suggests that the use of routine contact tracing data is a valid approach for the construction of sexual networks.

Chlamydia Infections↗
PubMed1979

Health-seeking behavior and social networks of the aged living in single-room occupancy hotels.

The elderly who reside in single-room occupancy (SRO) hotels often have been depicted as "isolates," lacking the interest or ability to engage primary or secondary support systems. This characterization has not enhanced understanding of how the SRO aged are able to survive in the community. With the use of network analysis techniques, this study demonstrates the inaccuracy of the assertion that these old persons lack significant social support. The data pointed to differences in network size, complexity, intensity, connectedness, and directionality in relation to varying degrees of physical and psychiatric health.

Aged↗
PubMed1996

Effect of preoperative donation of autologous blood on deep-vein thrombosis following total joint arthroplasty of the hip or knee.

The effect of preoperative donation of autologous blood on postoperative deep-vein thrombosis was retrospectively studied in men who had been managed consecutively with elective total joint replacement of the hip or knee because of osteoarthrosis. The patients had, on the average, two of nine considered risk factors for deep-vein thrombosis. Two hundred and thirty-seven patients were evaluated postoperatively with ascending venography, and they form the basis of this study. Fifty-four patients had venographic evidence of deep-vein thrombosis of the lower extremity, with most having asymptomatic clots distal to the knee. The prevalence of deep-vein thrombosis was nineteen (16 per cent) of 116 after total hip arthroplasty, compared with thirty-five (29 per cent) of 121 after total knee arthroplasty (chi square=4.6, p=0.03). Deep-vein thrombosis developed in twenty-eight (17 per cent) of the 161 patients who had donated blood preoperatively, compared with twenty-six (34 per cent) of the seventy-six patients who had not donated blood preoperatively (chi square=7.7, p=0.006). Through logistic regression analysis, the donation of autologous blood was shown to reduce significantly the development of postoperative deep-vein thrombosis for patients managed with total knee arthroplasty (p<0.01) but not for patients managed with total hip arthroplasty. Additional neural network analysis showed the donation of autologous blood to be the most important prognostic factor in predicting the absence of postoperative deep-vein thrombosis. In addition to diminishing the need for transfusion of homologous blood after total joint arthroplasty, preoperative donation of autologous blood appears to protect against postoperative deep-vein thrombosis after total knee arthroplasty.

Adult↗
PubMed1999

Artificial neural network-aided image analysis system for cell counting.

BACKGROUND: In histological preparations containing debris and synthetic materials, it is difficult to automate cell counting using standard image analysis tools, i.e., systems that rely on boundary contours, histogram thresholding, etc. In an attempt to mimic manual cell recognition, an automated cell counter was constructed using a combination of artificial intelligence and standard image analysis methods. METHODS: Artificial neural network (ANN) methods were applied on digitized microscopy fields without pre-ANN feature extraction. A three-layer feed-forward network with extensive weight sharing in the first hidden layer was employed and trained on 1,830 examples using the error back-propagation algorithm on a Power Macintosh 7300/180 desktop computer. The optimal number of hidden neurons was determined and the trained system was validated by comparison with blinded human counts. System performance at 50x and lO0x magnification was evaluated. RESULTS: The correlation index at 100x magnification neared person-to-person variability, while 50x magnification was not useful. The system was approximately six times faster than an experienced human. CONCLUSIONS: ANN-based automated cell counting in noisy histological preparations is feasible. Consistent histology and computer power are crucial for system performance. The system provides several benefits, such as speed of analysis and consistency, and frees up personnel for other tasks.

Cell Count↗
PubMedDate not supplied

Analysis of biofluids in aqueous environment based on mid-infrared spectroscopy.

In this study we describe a semiautomatic Fourier transform infrared spectroscopic methodology for the analysis of liquid serum samples, which combines simple sample introduction with high sample throughput. The applicability of this new infrared technology to the analysis of liquid serum samples from a cohort of cattle naturally infected with bovine spongiform encephalopathy and from controls was explored in comparison to the conventional approach based on transmission infrared spectroscopy of dried serum films. Artifical neural network analysis of the infrared data was performed to differentiate between bovine spongiform encephalopathy-negative controls and animals in the late stage of the disease. After training of artifical neural network classifiers, infrared spectra of sera from an independent external validation data set were analyzed. In this way, sensitivities between 90 and 96% and specificities between 84 and 92% were achieved, respectively, depending upon the strategy of data collection and data analysis. Based on these results, the advantages and limitations of the liquid sample technique and the dried film approach for routine analysis of biofluids are discussed.

Algorithms↗
PubMed2006

Time-dependent sensitivity analysis of biological networks: coupled MAPK and PI3K signal transduction pathways.

Sensitivity analysis has been widely used in the studies of complicated chemical reaction and biological networks, for example, in combustion studies and metabolic control analysis of pathways. In the latter cases, the responses of system properties at steady states with respect to changes of parameters, such as initial concentrations and rate constants, are often expressed as sensitivities. Besides steady-state sensitivities, time-dependent sensitivities should be useful; however, the explicit use of them in analyzing complicated biological systems has so far been limited. Using the coupled mitogen activated protein kinase (MAPK)-phophatidylinoisitol 3'-kinase (PI3K) system of the Ras pathways, known to be involved in about 30% of human cancers, as an example, we show that time-dependent sensitivities are useful for the studies of complex biological systems. They provide, for example, the following information: (a) multiple time scales existing in a complex system involving cross-talks and feedback loops; (b) the signs and strengths of responses to perturbations (as system complication increases, the signs of global responses are not always easily determined; for example, response may change sign more than once as time evolves); (c) beyond concentration dynamics, sensitivities revealing further details about the intricate dynamics and the effects of the cross-talks; (d) ranking of vulnerability of nodes of a biological network using integrated sensitivity-a first step toward the identification of drug targets; (e) reduced sensitivity serving as a measure of the stability or robustness of pathways. Our results indicate that the role of the PI3K branch in the coupled pathways is to enhance the robustness of the MAPK pathway. More importantly, they demonstrate that time-dependent sensitivity analysis can be a valuable tool in system biology.

Mitogen-Activated Protein Kinases↗
PubMedDate not supplied

Bioinformatics for the genomic sciences and towards systems biology. Japanese activities in the post-genome era.

The knowledge gleaned from genome sequencing and post-genome analyses is having a very significant impact on a whole range of life sciences and their applications. 'Genome-wide analysis' is a good keyword to represent this tendency. Thanks to innovations in high-throughput measurement technologies and information technologies, genome-wide analysis is becoming available in a broad range of research fields from DNA sequences, gene and protein expressions, protein structures and interactions, to pathways or networks analysis. In fact, the number of research targets has increased by more than two orders in recent years and we should change drastically the attitude to research activities. The scope and speed of research activities are expanding and the field of bioinformatics is playing an important role. In parallel with the data-driven research approach that focuses on speedy handling and analyzing of the huge amount of data, a new approach is gradually gaining power. This is a 'model-driven research' approach, that incorporates biological modeling in its research framework. Computational simulations of biological processes play a pivotal role. By modeling and simulating, this approach aims at predicting and even designing the dynamic behaviors of complex biological systems, which is expected to make rapid progress in life science researches and lead to meaningful applications to various fields such as health care, food supply and improvement of environment. Genomic sciences are now advancing as great frontiers of research and applications in the 21st century. This article starts with surveying the general progress of bioinformatics (Section 1), and describes Japanese activities in bioinformatics (Section 2). In Section 3, I will introduce recent developments in Systems Biology which I think will become more important in the future.

Animals↗
PubMed2003

A novel method for diagnosing chronic rhinosinusitis based on an electronic nose.

The nasal out-breath of persons with chronic nasal and/or paranasal infections may have characteristic strange odors, which in our experience are in most cases related to bacterial and/or fungal infections of the sinuses. The objective of the present study was to examine nasal out-breath samples from patients with chronic rhinosinusitis (CRS) (with or without polyposis) and healthy control volunteers using the electronic-nose (EN) technology. We developed a simple technique for collecting samples of nasal out-breath in disposable sterile plastic sacks with a tight closing seal. The principal component analysis correctly classified all individual EN patterns for CRS patients and misclassified 2 samples from the healthy controls (80.0% successful classification rate). The artificial neural network analysis correctly classified 60.0% of the patterns of both groups. We believe that the use of methodologies based on EN technology, combined with conventional clinical examinations, may improve the diagnosis of chronic rhinosinusitis.

Adult↗
PubMed2025

LncRNA Profiling and ceRNA Network Construction of Intrauterine Exosomes in Goats During Embryo Implantation.

Exosomes have been shown to play an important role in embryo implantation, but the mechanism is still unclear. This study aimed to investigate the functional roles of lncRNAs in intrauterine exosomes in goat pregnancy. We used RNA-seq to identify the lncRNA profiles of exosomes obtained from goat uterine rinsing fluid at 5, 15, and 18 days of gestation. In addition, we performed weighted gene co-expression network analysis based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs). Functional enrichment analyses of gene modules were conducted using Gene Ontology classification (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on predictive interaction derived from miRTarBase, miRDB and RNAhybrid databases. Altogether, 831 DELs were identified. GO and KEGG analysis showed that the target genes were enriched in processes associated with embryo implantation, such as signaling receptor activity, binding and immune response. Nine functional co-expression modules were enriched in various biological processes, such as metabolic pathways, protein transport, cell cycle and VEGF signaling pathway. Additionally, 12 lncRNA-mediated ceRNA networks were constructed. Our results demonstrate that exosomal lncRNAs in uterine flushing fluid exhibit dynamic changes across gestational stages and play an important role in regulating the uterine microenvironment during embryo implantation. These findings provide a foundational basis for screening exosome-derived lncRNAs that influence embryo implantation and contribute to elucidating the mechanistic roles of lncRNAs in exosome-mediated processes during early pregnancy.

embryo implantation↗
PubMed2002

Software for signaling networks, electronic and cellular.

Cellular signaling networks have many similarities with electronic circuits. Therefore, the tools used to test and analyze electronic circuits can be adapted to analyze cellular signaling processes. Lok describes some of these signaling network analysis tools, their underlying principles, and their limitations.

Feedback, Physiological↗