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PubMed2004

Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens.

Lineage trees of mutated rearranged Ig V region sequences in B lymphocyte clones often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation. In this study, we use a novel method for analyzing lineage tree shapes, using terms from graph theory to quantify the differences between primary and secondary diversification in rabbits and chickens. In these species, Ig gene diversification starts with rearrangement of a single (in chicken) or a few (in rabbit) V(H) genes. Somatic hypermutation and gene conversion contribute to primary diversification in appendix of young rabbits or in bursa of Fabricius of embryonic and young chickens and to secondary diversification during immune responses in germinal centers (GCs). We find that, at least in rabbits, primary diversification appears to occur at a constant rate in the appendix, and the type of Ag-specific selection seen in splenic GCs is absent. This supports the view that a primary repertoire is being generated within the expanding clonally related B cells in appendix of young rabbits and emphasizes the important role that gut-associated lymphoid tissues may play in early development of mammalian immune repertoires. Additionally, the data indicate a higher rate of hypermutation in rabbit and chicken GCs, such that the balance between hypermutation and selection tends more toward mutation and less toward selection in rabbit and chicken compared with murine GCs.

Algorithms↗

PubMed1999

[An analysis of the structure in material pictures of collage work].

The purpose of this study was to analyze the process by which collage material was chosen, by looking at the structure in material pictures in terms of their transitive chain and connection strength, and investigate the relationship between planning process and artwork characteristics. For the purpose, successive choices of material pictures were analyzed, and graph theory applied. Forty mentally retarded and normal subjects participated in an experiment of collage work production. The transitive chain of collage material pictures for normal subjects was long (deep) and showed story development, and connections among material pictures were strong. On the other hand, the chain for retarded subjects was short (shallow), without story development, and the connections weak. These results showed a correspondence between planning process and artwork characteristics. It was suggested that the method used in this study was effective in analyzing the structure of collage as well as Hakoniwa work.

Adult↗

PubMed1998

Conceptual integration of information databases into an Intranet.

Large information systems handle massive volume of data stored in heterogeneous sources of information. Each server has its own model of concepts representation with regard to its aims. One of the main problems encountered by end-users when accessing different servers is to match their own viewpoint on biomedical concepts with their various representations that are made in the database servers. The aim of the project ARIANE is to provide end-users with easy-to-use and natural means to access and query heterogeneous information databases. The objectives of this research work consist in building a conceptual interface by means of the Internet technology inside an enterprise Intranet, and to propose a method to realize it. Moreover, this method provides designers of web sites with a powerful tool to manage them on the basis of an ontology of the biomedical domain. This method is based on the knowledge sources provided by the Unified Medical Language System project of the U.S. National Library of Medicine and exploits intensively the conceptual graphs theory.

Computer Communication Networks↗

PubMed2000

Search for a new description of protein topology and local structure.

A novel description of protein structure in terms of the generalized secondary structure elements (GSSE) is proposed. GSSE's are defined as fragments of the protein structure where the chain doesn't radically change its direction. In this new language, global protein topology becomes a particular arrangement of the relatively small number of large, rod like GSSE's. Protein topology can be described by an adjacency matrix giving information, which GSSE's are close in space to each other and defining a graph, where GSSE's are equivalent to vertices and interactions between them to edges. The information about the local structure is translated into the local density of pseudo-Calpha atoms along the chain and the curvature of the chain. This new description has a number of interesting and useful features. For instance, enumeration theorems of graph theory can be used to estimate a number of possible topologies for a protein built from a given number of elements. Different topologies, including novel ones, can be generated from the known by various permutations of elements. Many new regularities in protein structures become suddenly visible in a new description. A new local structure description is more amenable to predictions and easier to use in fold predictions.

Animals↗

PubMed2000

Towards a complete map of the protein space based on a unified sequence and structure analysis of all known proteins.

In search for global principles that may explain the organization of the space of all possible proteins, we study all known protein sequences and structures. In this paper we present a global map of the protein space based on our analysis. Our protein space contains all protein sequences in a non-redundant (NR) database, which includes all major sequence databases. Using the PSI-BLAST procedure we defined 4,670 clusters of related sequences in this space. Of these clusters, 1,421 are centered on a sequence of known structure. All 4,670 clusters were then compared using either a structure metric (when 3D structures are known) or a novel sequence profile metric. These scores were used to define a unified and consistent metric between all clusters. Two schemes were employed to organize these clusters in a meta-organization. The first uses a graph theory method and cluster the clusters in an hierarchical organization. This organization extends our ability to predict the structure and function of many proteins beyond what is possible with existing tools for sequence analysis. The second uses a variation on a multidimensional scaling technique to embed the clusters in a low dimensional real space. This last approach resulted in a projection of the protein space onto a 2D plane that provides us with a bird's eye view of the protein space. Based on this map we suggest a list of possible target sequences with unknown structure that are likely to adopt new, unknown folds.

Algorithms↗

PubMed2002

An eigenvector method for estimating item parameters of the dichotomous and polytomous Rasch models.

The purpose of this paper is to describe a technique for obtaining item parameters of the Rasch model, a technique in which the item parameters are extracted from the eigenvector of a matrix derived from comparisons between pairs of items. The technique can be applied to both dichotomous and polytomous data. In application to a previously published data set, it is shown that the technique provides item parameter estimates comparable to those produced by joint maximum likelihood estimation, and for the most difficult items, the technique appears to produce superior estimates. This method has several advantages. It easily accommodates missing data, and makes transparent the basis for item parameter estimation in the presence of missing data. Furthermore, the method provides a link to other methods in the social sciences and, in particular, provides the framework for application of graph theory to the analysis of assessment networks. Finally, it exploits several characteristics that are unique to the Rasch model.

Algorithms↗

PubMed2000

De Novo Interpretation of MS/MS Spectra and Protein Identification via Database Searching.

Peptide sequencing via tandem mass spectrometry(MS/MS)is one of the most powerful tools in proteomics to identify proteins. A new algorithm was developed for de novo interpretation of MS/MS spectra using graph theory and dynamic alignment between real spectra and theoretical spectra. The trustworthy peptides from de novo interpretation were used in protein identification via database searching. A high throughput statistical analysis of SwissProt and TrEMBL protein databases showed that it's enough to identify a protein in database with three sequence tags of four amino acid residues, two sequence tags of five amino acid residues or one sequence tag of eight amino acid residues.

Journal Article↗

PubMed2002

A unified approach to joint modeling of multiple quantitative and qualitative traits in gene mapping.

Using graph theory, we present a theoretical basis for mapping oligogenes in the joint presence of multiple phenotypic measurements of both quantitative and qualitative types. Various statistical models proposed earlier for several traits of solely single type are special cases of the unified approach given here. Our emphasis is on the generality of the framework, without specifying explicit assumptions about a sampling design. When information about environmental factors potentially affecting the traits is available, it can be incorporated into the genetic model. We adopt the Bayesian inferential machinery due to its firm theoretical basis and its capability of handling uncertain quantities; such as unobserved model parameters, missing marker data, and even different putative genetic models, probabilistically within a single framework. It is shown here that biological hypotheses about single gene affecting simultaneously multiple traits (pleiotropy) can be intuitively imposed as parameter constraints, leading to pleiotropic models for which posterior probabilities can be calculated. Outline of the possible implementation of the Bayesian method is described using the general reversible-jump Markov chain Monte Carlo algorithm. Some future challenges and extensions are also discussed.

Animals↗

PubMed2000

Morphometric analysis of dendritic tree of cerebellar Purkinje-cells.

Basic neural processes of sensorimotor adaptation can be observed by cellular-level studies on cerebellar cortex, both by electrophysiological and morphological means. In earlier studies we demonstrated double (sometimes triple or quadruple) rhythmic prespike activity patterns in dendritic microelectrode records taken from cerebellar Pc. By their active and passive interactions, the actual input pattern will turn into an arrhythmic output spiking, realizing a nonlinear and phase-sensitive integration. This curious complex spike-generating process can give rise to novel cerebellar functional models. The acting membrane dynamics rely not just upon the ionic current machinery but also upon the specific micromorphology of the dendritic tree, especially that of the branching areas. Although, statistical analyses on Pc dendrites generally followed the graph-theory, elaborated abstract parameters for complexity and hierarchy, and denied realistic geometry. Thus a novel specific morphometric study should be carried out, first applied to the main branching sites.

Animals↗

PubMed1992

Analysis of spatial structure of thymocytes and of their contacts with thymic non-lymphoid cells.

The study aimed et determining morphological relations between thymic cells and thymocytes. The studies were performed on 16 days old rats of Wistar strain. The material was processed for ultrastructural studies in a routine manner. For 50 thymocytes computer reconstruction was performed which allowed to define cell volume, volume of cell nucleus and of condensed chromatin. The value characterizing three-dimensional morphology of thymocytes provided grounds for analysis using graph theory. The stereological methods allowed to examine microarchitecture of individual thymic zones. Thymocytes in contact with dendritic cells or with macrophages were found to differ in morphology from thymocytes with no such contacts. The results indicated direct effect of dendritic cells and of macrophages on thymocytes.

Animals↗

PubMed2004

Universal electronic health record MUDR.

One of the important research tasks of the European Centre for Medical Informatics, Statistics and Epidemiology - Cardio (EuroMISE Centre - Cardio) is the applied research in the field of electronic health record design including electronic medical guidelines and intelligent systems for data mining and decision support. The research in the field of data storage and data acquisition was inspired by several European projects and standards, mostly by the I4C and TripleC projects. Based on experience gathered during cooperation in the TripleC project we have proposed a description of a flexible information storage model. The motivation for this effort was the large variability of the set of collected features in different departments - including temporal variability. Therefore, a dynamically extensible and modifiable structure of items is needed. In our model we use two basic structures called the knowledge base and data files. The main function of the knowledge base is to express the hierarchy of collectable features - medical concepts, their characteristics and relations among them. The data files structure is used to store the patient's data itself. These two structures can be described using graph theory expressions. Based on this model, a three-layer system architecture named "Multimedia Distributed Record" (MUDR) has been proposed and implemented. During the implementation, modern technologies such as Web Services, SOAP and XML were used. For the practical usage of EHR MUDR, an intelligent application called MUDRc (MUDR Client) was created. It enables physicians to use EHR MUDR in a flexible way. During the development process, maximum emphasis was placed on user-friendliness and comfortable usage of this application. Several methods of data entry can be used: pre-defined forms, direct entry into the tree data structure of the EHR MUDR, or automatic unstructured free-text report parsing and data retrieval. The system enables fast and simple importing and exporting of data as well. The system integrates modern multimedia formats (X-ray photos, sonography and other pictures, video-sequences, audio records) as well as progressive methods of decision support systems realized by medical guidelines and other modules.

Artificial Intelligence↗

PubMed2005

Microarray annotation and biological information on function.

OBJECTIVES: Many methods for statistical analysis of gene expression studies by DNA microarrays produce lists of genes as output. To understand gene lists in terms of traditional biology, e.g. which pathways may be affected, it is necessary to get appropriate annotations for the probes on an array. METHODS: Problems arise with the different sources that have been used by manufacturers to design microarray probes, and their association to biological entities like genes, transcripts and proteins. Function annotation is of crucial importance, and systems like Gene Ontology can be used for this purpose. It arranges annotation terms in a hierarchical manner and thus makes annotations in a gene list amenable to automated analysis. RESULTS: Several methods for analyses of gene function are described. The hierarchical nature of systems like Gene Ontology particularly suggests using methods from graph theory. CONCLUSIONS: The main problem in annotating microarray probes and inferring affected functional modules is the incompleteness and degree of error in current biological databases. Initial approaches to make use of functional annotation exist, but have to be extended, in particular with respect to estimating the statistical significance of results.

Computational Biology↗

PubMed2006

[Automatic diagnosis of malignant degree of brain glioma based on Bayesian network].

Bayesian network connects graph theory with statistics, being an important research direction in data mining. Compared with other approaches used for data mining, Bayesian network can combine prior knowledge with observed data. Besides that, it can handle incomplete data sets. This paper applies Bayesian network to predict the malignant degree of brain glioma. Totally 280 cases are collected, and some of them contain missing values. Preprocessing is taken to make them applicable to the algorithms. Unlike MLP network, both Bayesian network and decision tree use attribute-value pairs to represent diagnostic knowledge derived from treated cases. These could improve both the understandability and applicability of their results. Results of all these algorithms can achieve accuracy rate over 80%, which satisfies the requirement of neuroradiologists.

Bayes Theorem↗

PubMed1990

Analysis of multiscale biochemical systems: graph methods.

The applicability of usual biochemical modelling by ordinary differential equations is restricted if some of the metabolite concentrations leave the range of observability during the time span of interest. Therefore, a method is needed for testing whether the solution of a differential equation system remains comparable with given reference concentrations, which depend on the conditions of measurement. In the present paper, such a method based on graph theory and non-standard analysis is developed for the special case of networks of monomolecular reactions endowed with linear kinetics.

Algorithms↗

PubMed1990

Classification applied to smears in hormone cytology.

Hormone cytology smears have been classified using a standard method of graph theory. The Euclidean distance was chosen as a suitable measure of the dissimilarity between smears. Maximum cliques were defined as groups to which no further element can be added without invalidating the group-defining distance. Both the type and number of cells found in the smear influence the classification. The absolute number of cells appears to be especially appropriate for the discrimination of the different proliferation stages of vaginal epithelium. However, the elaboration of an adequate sampling procedure is necessary for obtaining smears from the lateral wall of the vagina, as well as for the improved preparation of the smears themselves.

Female↗

PubMed1987

Analysis of adenomatous structures in histopathology.

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

Adenocarcinoma↗

PubMedDate not supplied

[Effective method for physical mapping the DNA molecule].

The method of DNA molecules physical mapping based on the algorithms of discrete optimization and graph theory was proposed. The input information consisted of the sizes of single and double restrictions fragments and the level of their measurement errors. The method presents possibilities for optimal planning of experiments and step by step construction of physical maps. Efficiency of the method and examples of its application are discussed.

DNA↗

PubMedDate not supplied

[Kinetic manifestations of slow conformation rearrangements of lactate dehydrogenase. An experiment and a mathematical model].

Non-steady-state kinetics of lactate dehydrogenase (LDH) catalyzed reaction was investigated for a wide time interval (from 100 msec to 1-3 min) by using stopped-flow methods. A two-stage character of LDH reaction, slow changes like a lag-period on kinetic curves at pH 8.0, flexions on kinetic curves after pre-mixing LDH with NAD+ and pyruvate have been revealed. The graph theory for mathematical analysis of experimental data was applied, which has been developed for the non-steady-state kinetics. An enzyme model of the two-conformer LDH structure was used. The reaction scheme with a preferential inhibition of one of the conformers (pH 8.0) is suggested. The obtained values of kinetic constants prove that transitions between LDH conformers must be slow.

Animals↗