Bioinformatics Sciences Projects . Novosibirsk. Siberian Branch of Russian Academy of Science
List of ProjectsProject description
The Project is devoted to establishment of a high performance network linking scientists from the U.S. and Russian Federation. The Institute of Cytology and Genetics of SB RAS has broad cooperation with American partners. One of the Projects is entitled "Developing modeling and bioinformatics" and sponsored by the NSF Frontiers in Integrative Biological Research (FIBR) Program.
By integrating advances in biological knowledge, biological instrumentation, applied biomathematics, and computing, the authors of this proposal will create a computational modeling tool for developmental biology research. This effort requires a multidisciplinary, multi-institutional team, which will integrate advances in mathematical models of cell regulation and development, plant developmental biology, and software architectures to produce a scalable software platform for research and educational outreach related to the developmental biology of the shoot apical meristem in Arabidopsis and more generally to the study of complex developmental biological systems.
The research under the Project will be done at the edge of two different areas of modern science: systemic biology integrating mathematics, bioinformatics, genomics, computer and systems science and developmental biology. As a result, we propose to create a first, scalable version of a general tool and to demonstrate its success in appropriate developmental biological systems beginning with plants. In greater detail, we propose a multi-disciplinary and multi-institutional team which will integrate advances in mathematical models of cell regulation and development, plant developmental biology, microscopy, image processing, bioinformatics, and intelligent software architectures, to produce a software platform capable of contributing first to the developmental biology of the shoot apical meristem (SAM) in Arabidopsis and then more generally to the study of complex developmental biological systems.
The scientific objectives of this effort also include achieving a quantitative scientific understanding of developmental systems in Arabidopsis, starting with the shoot apical meristem stem cell population and phyllotaxis. Realistic computational models of stem cell behaviour in shoot apical meristems, and of organ positioning around the shoot apical meristem, will provide software of use in modelling of development in other organisms, and in modelling any complex set of processes in multicellular tissues. It will also provide a highly specific mechanistic description and model of key aspects of plant development, Refinement and extension of the model will eventually lead to a “silicon plant,” a complete systems model of gene activity and its consequences in plant growth and development.
Another objective of the project is to study complex hierarchy of system development. In particular, shoot apical meristem development will be represented as a hierarchical system of minimal models. T his system should be self-consistent, that is, conclusions that were obtained for a model at one hierarchical level could be interpreted as the limitations for the model of the higher hierarchical level. To this aim, we plan to apply Petri nets that are useful for modeling of complex systems with parallel architecture and synchronization of events. These features are of especial importance for administration of biological systems at different levels, from gene expression, to protein synthesis, toward organism level and higher. Experimental data representation in a form of Petri nets will give some advantages, since numerous software programs are known for Petri nets analysis. Under construction of hierarchical Petri net system, the main attention will be paid to genetic systems controlling cell proliferation and differentiation, as well as to spatio-temporal interaction between these two basic processes during shoot apical meristem development.
During the Project implementation, Russian and American sides will get mutual benefits. American Partner has a great experience in studying genetic control of shoot apical meristem function in development. They have analyzed a number of mutations that affect shoot meristem size and growth, shoot apical meristem formation, and activities of floral meristems that relate to shoot apical meristem cell division patterns, have been isolated, studied in detail at the phenotypic level, cloned, and studied in detail at the molecular level. Russian team has independent but very compatible capabilities in pathway and expression informatics, so exchange of software will not be required in order to pool mutual efforts on the representation, in SBML, of broad plant development pathway knowledge and on the development of scalable regulatory network inference algorithms for plant development.
The expected outcome of the proposed work is a computational model of the developing and growing shoot apical meristem of Arabidopsis (and thus, presumably, of any dicotyledonous plant). This model will be based on microscopic observations of the cellular domains and cell division patterns in the SAM in mutants and wild-type, and will be detailed enough to allow prediction of mutant phenotypes, and therefore experimental tests of the model. The computational model will itself be adaptable to other situations of cell-cell signaling in solid tissues, and will therefore serve as the basis for a new generation of studies, in vivo and in silico, of growth and development in plants and in animals. Refinement and extension of the model will eventually lead to a “silicon plant,” a complete model of gene activity and its consequences in plant growth and development. The outreach component of the proposal is designed to raise public awareness of the critical importance of cells in plants and animals, and therefore to introduce students and adults to one of the fundamental pillars of modern biology – the understanding of which is essential for citizens to understand their own bodies and cellular processes, including illnesses such as cancer.
Broader Impact: the goal of the outreach plan is to develop, evaluate, and introduce a new set of techniques for high school and pre-service science teachers. Ultimately this will put fundamental, powerful new capabilities in the hands of the biotechnology industry.
Leaders from Russian side
- RAS Corresponding Member Nikolay Kolchanov (kol@bionet.nsc.ru),
- RAS Corresponding Member Anatoly Fedotov (fedotov@sbras.ru)
- Grant Programs of the Russian Foundation for Basic Research (No. 01-07-90376,
01-07-90084, 02-07-90355, 02-07-90359, 03-07-90181-_, 03-04-48506-_, 03-04-48469-_, 03-04-48555-_,
03-07-96837, 03-07-96833-_2003)
- Grant Programs of Russian Ministry of Industry, Sciences and Technologies (No. 43.073.1.1.1501),
- Grant Programs of Siberian Branch of the Russian Academy of Sciences (Integration Projects
Nos.119, 145, 142),
- Subcontract of the National Institutes of Health USA (No.2 R01-HG-01539-04A2).
- Scientific Inference Systems Laboratory Institute for Genomics and Bioinformatics
- University of California Irvine California Institute of Technology 1200 East California Boulevard Pasadena, California 91125
The main research Vector activities in bioinformatics are focused in:
Development of mathematical models in biotechnology, virology, immunology, ecology, molecular biology and aerobiology so as development of software supporting the models, development of databases in many fields, development of knowledge based systems in biotechnology, virology, and molecular biology.- Development of GigaGene Technology: a search for new genetic elements in the human genome
(Dr. Vladimir Blinov, e-mails: vblinov@online.nsk.ru)
A new matrix visual technology GigaGene allows superlong sequences of complete genomes of bacteria, viruses, and human chromosomes to be analyzed. In particular, this technology allows detecting automatically all the direct and inverted repeats of such sequences and displaying them in a compact fashion that conveys fold back structure. The technology includes algorithms, software, research technique and methods for comparing and analysis of genes sequences. Logically, the architecture of GigaGene technology based on well developed in "Vector" MegaGene and MegaDNA technologies and using both high performance computations and data compression.
The result will be a software package, which analyzes digital sequence data (nucleotides) and displays repeats and their hierarchical structure interactively. The package should be as portable as possible, so it should be in a standard language, such as C++ with modular design, to allow for rapid conversion of Graphical User Interface (GUI) features between PC, Mac and Unix-X windows systems. Definitely high performance parts of the software will be oriented to concrete computing system.
At present the proposal have been prepared for development of GigaGene Technology (manager of project: Dr. Vladimir Blinov, e-mails: vblinov@online.nsk.ru).
- Investigation of orthopoxviruses (Domestic Collection of Variola Virus Strains) –
Professor Sergei Shchelkunov, e-mail: snshchel@vector.nsc.ru
These studies include comparative phylogenetic analysis of structure and molecular evolution of orthopoxvirus genomes as well as sequencing and analysis of the genes determining virulence of orthopoxviruses (for example variola virus) and genes encoding some structural proteins. These investigations allowed accumulating the information on structures of the genes and performing their comprehensive computer analysis. The sequencing data formed the background f or comparing the nucleotide sequences of the corresponding genes.
- Methods and software for analysis of structure-activity relationship in families of homologous
proteins and designing of artificial proteins with improved medical and biological properties
(Dr Vladimir Ivanisenko, e-mails: salix@bionet.nsc.ru)
Mutations in human TNF-_, lowering cytotoxic activity and ensuring prolonged action of the modified proteins, have been proposed. An experimental verification of properties of the proposed mutants of TNF-_ has shown the complete conformity of experimental data with the theoretical predictions.
A relationship between ability of self-assembly of virus particles of bacteriophages M13, f1 and Fd and the presence of positively charged amino acids in the foreign insertions of surface proteins has determined. Analysis of foreign epitopes inserted in HBcAG for solving the problem of chimerical core particle self-assembly was carried out.
These investigations were based on programs ProAnalyst, ProAnal, SADC, PRANA, Salix that allow to reveal sites, whose physical-chemical characteristics correlate with activities of proteins or other their properties.
- An algorithm and computer program EpIdRPL for calculation of sets of peptides, which are able
according to stereochemical rules to be conformationally identical to surface part of proteins.
- GArna - an Internet interactive tool for RNA folding simulation by genetic algorithm and a
steepest descent.
- Structure-based design of peptides mimicking protein functional sites and antigenic epitopes
(Dr Vladimir Ivanisenko, e-mails: salix@bionet.nsc.ru)
An algorithm and computer program EpIdRPL for calculation of sets of peptides, which are able according to stereochemical rules to be conformationally identical to surface part of proteins.
- Technology for searching of regions in virus proteins that have local similarities with human
proteins (Dr Amir Maksyutov, e-mail: maksyutov@vector.nsc.ru; Dr Alexander Bachinsky,
e-mail: bachin@vector.nsc.ru;
Dr Sergei Bazhan, e-mail: bazhan@vector.nsc.ru)
Fragments of HIV-1, Ebola, Marburg, Hepatitis and other viral proteins having high similarity with human proteins have been revealed. Some of these outcomes could spill light on gears of pathogenicity of these infections and form the basis of rational designing of vaccines.
- Theoretical design of artificial polyepitope B and T cell immunogens, candidates for use as
peptide and DNA vaccines (Dr Amir Maksyutov,
e-mail: maksyutov@vector.nsc.ru; Dr Sergei Bazhan,
e-mail: bazhan@vector.nsc.ru)
- Databank of protein family patterns PROF_PAT for detecting conserved motifs
(Dr Alexander Bachinsky, e-mail: bachin@vector.nsc.ru)
Motifs of patterns, which had the minimum level of probability to be found in random sequences, were selected. Flexible fast search program accompanies the database of patterns. It allows treat thousands of amino acid sequences in a few minutes. The researcher can specify a similarity matrix (the type PAM, BLOSUM and other). Variable levels of similarity can be set (permitting search strategies ranging from exact matches to increasing levels of "fuzziness").
- Mathematical model of epidemics (Dr Alexander Bachinsky,
e-mail: bachin@vector.nsc.ru)
The model allows one to estimate spreading of infections in dependence on population structure, characteristics of infectious agent, and response actions. Effectiveness of these actions was investigated for smallpox outbreaks.
- Research into ecologo-epidemiological impacts of various anthropogenic contaminants of the
environment, development of new methodic approaches to their analysis, and creation of the
appropriate program-algorithmic complexes intended for the formation of databases. The program
complex ALGOS-SMOG (Dr Alexander Borodulin,
e-mail: borodulin@vector.nsc.ru) serves to:
- Determination of the correlation between characteristics of environment set by user and the
health structure of the groups of population under study;
- Evaluation of the contribution of each ecological factor and a given set of the factors to
the changes of health characteristics of population;
- Development of integral characteristics for environment quality and population
health;
- Evaluation of the degree of ecological heterogeneity of an area.
- Determination of the correlation between characteristics of environment set by user and the
health structure of the groups of population under study;
- Expert system for selection of processes for cell cultivation of animal cells and viruses
(Dr Alexander Bachinsky, e-mail: bachin@vector.nsc.ru;
Dr Sergei Bazhan, e-mail: bazhan@vector.nsc.ru)
On the basis of such facts as a type of the product (a biomass of viable cells, a protein or a low weight compound produced by the cells or a virus reproduced in the cell culture), scale of cultivation, sensitivity of the cells to shear forces, mode of the product processing, and other, during a session of the consultation, the system selects optimal combinations of reactor type, method of cultivation and substrate (carrier) for attachment and growth of cells (including suspension). The expert system can give an estimation of expediency of application of configurations specified by user.
- Expert system for estimation of pathogenic results of interactions of infectious agents in
mixed infections (Dr Alexander Bachinsky, e-mail: bachin@vector.nsc.ru)
The system estimates such characteristics as severity of the disease, state of defense systems, pathologic damages, and some other ones, including epidemic parameters. These estimations based on 35 characteristics of main pathogenic agent and on 68 characteristics of an agent that interferes with the pathogen.
Today SRC VB VECTOR has 39 active international projects. These projects involve close collaboration with CRDF, US Department of Energy, DARPA (Defense Advanced Research Projects Agency), CTR (the Cooperative Threat Reduction Program of the U.S. Department of Defense), USDA (U.S. Department of Agriculture/Agricultural Research Service),
(U.S. Department of Health and Human Services Biotechnology Engagement Program), as well as with the US leading scientific research centers.
Major areas of research pursued under international projects:
- development of vaccines against HIV/AIDS; influenza, measles;
- development of edible vaccines based on transgenic plants;
- investigation of genetic variability of genomes of viruses circulating in the territory of Russia (viral hepatitides; measles, mumps, Crimean-Congo hemorrhagic fever, West Nile etc.);
- discovery and screening of antivirals to include antivirals against smallpox virus;
- diagnosis of drug-resistant TB strains;
- development of novel approaches in TB therapy.
Protein and associated topics databases
- Swiss-Prot - Swiss-Prot annotated protein sequence db
- PMD - Protein Mutant db
- InterPro - Integrated Resources of Proteins Domains and Functional Sites
- PROSITE - PROSITE dictionary of protein sites and patterns
- PRINTS - Protein Motif fingerprint db
- ProDom - Protein domain db (Automatically generated)
- PROTOMAP - An automatic hierarchical classification of Swiss-Prot proteins
- SBASE - SBASE domain db
- SMART - Simple Modular Architecture Research Tool
- TIGRFAMs - TIGR protein families db
- BIND - Biomolecular Interaction Network db
- DIP - Db of Interacting Proteins
- MINT - Molecular INTeractions
- ProNet - Protein-Protein interaction db


