In Silico Biology - Volume 2, issue 2

Authors: Hofestädt, Ralf Hofestädt Ralf | Kolchanov, Nikolay | Reinitz, John

Article Type: Other

Citation: In Silico Biology, vol. 2, no. 2, pp. 35-36, 2002

Authors: Freier, Andreas | Hofestädt, Ralf | Lange, Matthias | Scholz, Uwe | Stephanik, Andreas

Article Type: Research Article

Abstract: REGARDING MOLECULAR BIOLOGY, WE SEE AN EXPONENTIAL GROWTH OF DATA AND KNOWLEDGE. AMONG OTHERS, THIS FACT IS REFLECTED IN MORE THAN 300 MOLECULAR DATABASES WHICH ARE READILY AVAILABLE ON THE INTERNET. THE USAGE OF THESE DATA REQUIRES INTEGRATION TOOLS CAPABLE OF COMPLEX INFORMATION FUSION PROCESSES. THIS PAPER WILL PRESENT A NOVEL CONCEPT FOR USER SPECIFIC INTEGRATION OF LIFE SCIENCE DATA. OUR APPROACH IS BASED ON A MEDIATOR ARCHITECTURE IN CONJUNCTION WITH FREELY ADJUSTABLE DATA SCHEMES. THE …IMPLEMENTED PROTOTYPE IS CALLED BIODATASERVER AND CAN BE ACCESSED ON THE INTERNET: HTTP://INTEGRATION.GENOPHEN.DE. TO REALIZE A COMFORTABLE USAGE OF THE RESULTED DATA SETS OF THE INTEGRATION PROCESS, A SQL-BASED QUERY LANGUAGE AND A XML DATA FORMAT WERE DEVELOPED AND IMPLEMENTED. Show more

Keywords: DATA INTEGRATION, DATA FUSION, MEDIATOR, WRAPPER

Citation: In Silico Biology, vol. 2, no. 2, pp. 37-57, 2002

Authors: Schreiber, Falk

Article Type: Research Article

Abstract: Biochemical reactions form large and complex networks. Comprehensible visual representations of these networks help biochemists understand the relationships between the chemical components. Typically pathway diagrams are manually produced drawings. Because of the steady progress of knowledge and the complex relationships in these networks, automatic visualizations are necessary. BioPath is a system for the exploration and automatic visualization of biochemical pathways. It has been developed to obtain an electronic version of the well-known …Boehringer Biochemical Pathways poster and offers new possibilities to find information and to navigate through pathways. BioPath has a specific database containing reactions and a hierarchical clustering of reactions and reaction networks. One feature is the automatic generation of pathways from the database and their high quality visualization. This paper states the requirements for the visualization of biochemical pathways, presents a layout algorithm and shows how BioPath can be used to explore biochemical reaction networks. Show more

Keywords: graph drawing , metabolic pathways, visualization, biochemical pathways

Citation: In Silico Biology, vol. 2, no. 2, pp. 59-73, 2002

Authors: Rojas, Isabel | Bernardi, Luca | Ratsch, Esther | Kania, Renata | Wittig, Ulrike | Saric, Jasmin

Article Type: Research Article

Abstract: To provide support for the analysis of biochemical pathways a database system based on a model that represents the characteristics of the domain is needed. This domain has proven to be difficult to model by using conventional data modelling techniques. We are building an ontology for biochemical pathways, which acts as the basis for the generation of a database on the same domain, allowing the definition of complex queries and complex data representation. The ontology is …used as a modelling and analysis tool which allows the expression of complex semantics based on a first-order logic representation language. The induction capabilities of the system can help the scientist in formulating and testing research hypotheses that are difficult to express with the standard relational database mechanisms. An ontology representing the shared formalisation of the knowledge in a scientific domain can also be used as data integration tool clarifying the mapping of concepts to the developers of different databases. In this paper we describe the general structure of our system, concentrating on the ontology-based database as the key component of the system. Show more

Keywords: Mycoplasma pneumoniae , biochemical pathways, database, ontology

Citation: In Silico Biology , vol. 2, no. 2, pp. 75-86, 2002

Authors: Hagelsieb, Gabriel Moreno | Collado-Vides, Julio

Article Type: Research Article

Abstract: We have previously demonstrated that genes within experimentally characterized operons of Escherichia coli are conserved together in other genomes more frequently than genes at the borders of transcription units. Here we expand the analyses and show that, as the phylogenetic distance of the genomes compared increases, the genes remaining together must belong to genes associated into operons in other prokaryotes regardless of the operon organization of the corresponding orthologous gene pair of E. coli. At the …same time, we show that the observed tendencies of genes within operons to keep very short inter-genic distances in E. coli, is the same in any other prokaryote whose genome is currently available. We also show the relationship between our analyses of conservation and the inference of functional relationships from genomic context. Show more

Keywords: genome context, functional relationship, operon conservation, intergenic distance

Citation: In Silico Biology, vol. 2, no. 2, pp. 87-95, 2002

Authors: Kolchanov, Nikolay A. | Nedosekina, Eugenia A. | Ananko, Elena A. | Likhoshvai, Vitaly A. | Podkolodny, Nikolay L. | Ratushny, Alexander V. | Stepanenko, Irina L. | Podkolodnaya, Olga A. | Ignatieva, Elena V. | Matushkin, Yury G.

Article Type: Research Article

Abstract: Almost all cellular processes in an organism are controlled by gene networks. Here we report on the analysis of gene networks functioning using two associated methods - data accumulation in GeneNet system and generalized chemical kinetic method for mathematical simulation of gene network functional dynamics. The technology of the usage of these methods is shown on the example of the gene network of macrophage activation.

Keywords: gene network, modeling, mathematical simulation, database designing, macrophage

Citation: In Silico Biology , vol. 2, no. 2, pp. 97-110, 2002

Authors: Jaeger, Johannes | Goodwin, Brian C.

Article Type: Research Article

Abstract: Kinetic modeling of developmental dynamics requires detailed knowledge about genetic and metabolic networks that underlie developmental processes. However, such knowledge is not available for a vast majority of developmental processes. Here, we present an coarse-grained, phenomenological model of periodic pattern formation in multicellular organisms based on cellular oscillators (CO) that can be applied to systems for which little or no molecular data is available. An oscillatory process within cells serves as a …developmental clock whose period is tightly regulated by cell-autonomous and non-autonomous mechanisms. A spatial pattern is generated as a result of an initial temporal ordering of the cell oscillators freezing into spatial order as the clocks slow down and stop at different times or phases in their cycles. When applied to vertebrate somitogenesis, the CO model can reproduce the dynamics of periodic gene expression patterns observed in the presomitic mesoderm. Different somite lengths can be generated by altering the period of the oscillation. There is evidence that a CO-type mechanism might also underlie segment formation in certain invertebrates, such as annelids and short germ insects. This suggests that the dynamical principles of sequential segmentation might be equivalent throughout the animal kingdom although most of the genes involved in segment determination differ between distant phyla. Show more

Keywords: segmentation, somitogenesis, short-germ band insects, cellular oscillators , phenomenological modeling, coarse-grained modeling, evolution of development, developmental dynamics

Citation: In Silico Biology, vol. 2, no. 2, pp. 111-123, 2002

Authors: Kozlov, Konstantin | Myasnikova, Ekaterina | Pisarev, Andrei | Samsonova, Maria | Reinitz, John

Article Type: Research Article

Abstract: We apply the fast redundant dyadic wavelet transform to the spatial registration of two-dimensional gene expression patterns of 736 Drosophila melanogaster embryos. This method is superior to the Fourier transform or windowed Fourier transform because of its ability to reduce noise and is of high resolution. In registration of …the dataset we use two cost functions based on computing the Euclidean or Mahalanobis distance. The algorithm shows a high level of accuracy. For early temporal classes the cost function based on Mahalanobis distance gives better results. We have reported a method for construction of an integrated dataset elsewhere. In this paper the method is extended to the two-dimensional case. The procedure for data assembly provides for the preservation of some aspects of the nuclear structure of a two-dimensional gene expression pattern. It is based on creating an averaged model that reproduces the spatial distribution of nuclei over the embryo image. The average concentrations of each protein in each averaged nucleus are computed from the series of embryos of the same age. Show more

Keywords: registration , wavelets, segmentation, Drosophila, gene expression patterns

Citation: In Silico Biology , vol. 2, no. 2, pp. 125-141, 2002

Authors: Arrigo, Patrizio | Ivaldi, Giovanni | Cardo, Pasquale Paolo

Article Type: Research Article

Abstract: The functional characterization of available genomic sequences is the major task of the research in the post-genome era. This complex task requires an integrative approach of high-throughput systems with in vitro and in vivo models in order to have a reliable evaluation of the biological function. The oligonucleotide antisense technology is one of the most promising approaches for the investigation of gene function; the crucial point of antisense experiments is the identification of optimal target sites …for hybridisation. In this paper we have applied a bioinformatic tool for the recognition of optimal antisense targets. In order to evaluate the effect of mutational events on target selection we have tested the program on a sample of human ?-hemoglobin variants. The proposed algorithm software will be integrated in a web based tool at the site: http://www.nettab.org/agewa Show more

Keywords: Antisense , oligonucleotide, hybridisation, point mutation, molecular diagnostic, gene functionalization, artificial neural networks, unsupervised learning

Citation: In Silico Biology , vol. 2, no. 2, pp. 143-150, 2002

Authors: Cooper, Mark | Chapman, Scott C. | Podlich, Dean W. | Hammer, Graeme L.

Article Type: Research Article

Abstract: In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that …underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes. Links: http://pig.ag.uq.edu.au/qu-gene/ http://www.apsru.gov.au/Products/apsim.htm Show more

Keywords: E(NK) model, epistasis, genotype-by-environment interactions, plant , crop, target population of environments, genetic space

Citation: In Silico Biology, vol. 2, no. 2, pp. 151-164, 2002