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Biomedical subjects

M P Ponomarenko

Publications and source records attributed to M P Ponomarenko.

At least 19 recordsLinked to original sources
PubMed2001

ACTIVITY: a database on DNA/RNA sites activity adapted to apply sequence-activity relationships from one system to another.

ACTIVITY is a database on DNA/RNA site sequences with known activity magnitudes, measurement systems, sequence-activity relationships under fixed experimental conditions and procedures to adapt these relationships from one measurement system to another. This database deposits information on DNA/RNA affinities to proteins and cell nuclear extracts, cutting efficiencies, gene transcription activity, mRNA translation efficiencies, mutability and other biological activities of natural sites occurring within promoters, mRNA leaders, and other regulatory regions in pro- and eukaryotic genomes, their mutant forms and synthetic analogues. Since activity magnitudes are heavily system-dependent, the current version of ACTIVITY is supplemented by three novel sub-databases: (i) SYSTEM, measurement systems; (ii) KNOWLEDGE, sequence-activity relationships under fixed experimental conditions; and (iii) CROSS_TEST, procedures adapting a relationship from one measurement system to another. These databases are useful in molecular biology, pharmacogenetics, metabolic engineering, drug design and biotechnology. The databases can be queried using SRS and are available through the Web, http://wwwmgs. bionet.nsc.ru/systems/Activity/.

Binding Sites↗
PubMed2001

rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations.

rSNP_Guide is a novel curated database system for analysis of transcription factor (TF) binding to target sequences in regulatory gene regions altered by mutations. It accumulates experimental data on naturally occurring site variants in regulatory gene regions and site-directed mutations. This database system also contains the web tools for SNP analysis, i.e., active applet applying weight matrices to predict the regulatory site candidates altered by a mutation. The current version of the rSNP_Guide is supplemented by six sub-databases: (i) rSNP_DB, on DNA-protein interaction caused by mutation; (ii) SYSTEM, on experimental systems; (iii) rSNP_BIB, on citations to original publications; (iv) SAMPLES, on experimentally identified sequences of known regulatory sites; (v) MATRIX, on weight matrices of known TF sites; (vi) rSNP_Report, on characteristic examples of successful rSNP_Tools implementation. These databases are useful for the analysis of natural SNPs and site-directed mutations. The databases are available through the Web, http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/.

Binding Sites↗
PubMed2000

SELEX_DB: an activated database on selected randomized DNA/RNA sequences addressed to genomic sequence annotation.

SELEX_DB is a novel curated database on selected randomized DNA/RNA sequences designed for accumulation of experimental data on functional site sequences obtained by using SELEX and SELEX-like technologies from the pools of random sequences. This database also contains the programs for DNA/RNA functional site recognition within arbitrary nucleotide sequences. The first release of SELEX_DB has been installed under SRS and is available through the WWW at http://wwwmgs.bionet.nsc.ru/mgs/systems/selex/

DNA↗
PubMed1999

Point mutations within 663-666 bp of intron 6 of the human TDO2 gene, associated with a number of psychiatric disorders, damage the YY-1 transcription factor binding site.

Single base mutations G-->A at position 663 and G-->T at position 666 of intron 6 of the human tryptophan oxygenase gene (TDO2) are associated with a variety of psychiatric disorders [Comings, D.E. et al. (1996) Pharmacogenetics 6, 307-318]. Binding of rat liver nuclear extract proteins to synthetic double-strand oligonucleotides corresponding to three allelic states of the region between 651 bp and 680 bp of human TDO2 intron 6 has been studied by gel shift assay. It has been demonstrated that to each allelic state of the region there corresponds a specific set of proteins that interacts with it. With the aid of computer analysis and using specific anti-YY-1 antibodies it has been shown that both mutations damage the YY-1 transcription factor binding site.

Animals↗
PubMed1998

GeneExpress: a computer system for description, analysis, and recognition of regulatory sequences in eukaryotic genome.

GeneExpress system has been designed to integrate description, analysis, and recognition of eukaryotic regulatory sequences. The system includes 5 basic units: (1) GeneNet contains an object-oriented database for accumulation of data on gene networks and signal transduction pathways and a Java-based viewer that allows an exploration and visualization of the GeneNet information; (2) Transcription Regulation combines the database on transcription regulatory regions of eukaryotic genes (TRRD) and TRRD Viewer; (3) Transcription Factor Binding Site Recognition contains a compilation of transcription factor binding sites (TFBSC) and programs for their analysis and recognition; (4) mRNA Translation is designed for analysis of structural and contextual features of mRNA 5'UTRs and prediction of their translation efficiency; and (5) ACTIVITY is the module for analysis and site activity prediction of a given nucleotide sequence. Integration of the databases in the GeneExpress is based on the Sequence Retrieval System (SRS) created in the European Bioinformatics Institute.

Artificial Intelligence↗
PubMed1997

Generating programs for predicting the activity of functional sites.

The computer system ACTIVITY is intended for generating programs with which to predict the activity of functional sites by nucleotide sequences. ACTIVITY analyzes a basis set of nucleotide sequences with known activity. The novelty of this approach is that Zadeh's fuzzy logic and decision-making theory have been employed for determining the best "sequence-->activity" regression. The best one thus determined is then transformed into the text of a program with which the activity for any nucleotide sequence is to be predicted. Testing with independent data has proved this prediction reliable. We have compared our approach with the two commonly used on identical data sets to find the ACTIVITY-generated programs quite competitive.

Database Management Systems↗
PubMed1997

Search for DNA conformational features for functional sites. Investigation of the TATA box.

A method for search of DNA conformational features significant for functional sites is developed. The method uses helical angles averaged for known X-ray structures. Nucleotide sequences are assigned mean angles in a given region. Choice of the significant angles is based on their capabilities to discriminate functional sites from random sequences. The yeast, invertebrate and vertebrate TATA boxes are analyzed using this method. Regions neighboring the TATA boxes are found to have smaller helical twist and roll angles. The results agree with the experimental data on Dickerson-Drew dodecamers. There is a significant decrease in the length of a small roll angle region with increasing complexity of taxon organization.

Animals↗
PubMed1993

SITEVIDEO: a computer system for functional site analysis and recognition. Investigation of the human splice sites.

We developed the computer system SITEVIDEO for analysis and recognition of the functional sites in DNA and RNA molecules. It reveals contextual features essential for site function and thus enable the user to design efficient methods for recognition of the functional sites. We mainly considered only quantitative characteristics reflecting the uneven distribution of oligonucleotides in the sequences of functional sites of interest. The approach suggested makes use of available information about the hierarchical organization of the functional sites, and ensures highly precise prediction of the sites. The present analysis is concerned with the human donor and acceptor splice sites. A method for recognizing these sites in the sequences with an accuracy of approximately 90% was developed.

Algorithms↗
PubMedDate not supplied

Nucleosomal DNA property database.

MOTIVATION: Chromatin structure plays the crucial role in proper gene functioning. Therefore, it is very important to investigate nucleosomal DNA properties and recognize genome nucleosome positioning sequences. Nevertheless, applying different sequence analysis methods separately is insufficient for complete nucleosomal DNA description. One of the most probable reasons for that is the weakness of nucleosome positioning signals. The present paper offers a set of methods to reveal the most important nucleosomal DNA characteristics and to show a common pattern of nucleosome site properties. RESULTS: A complex approach was used to determine conformational and physicochemical properties that are most significant for nucleosome binding site description. The integrated database of nucleosomal DNA properties is compiled. This database comprises different sections for description of DNA characteristics. Revealing significant DNA characteristics allows the classification of various samples of site sequences and the generation of programs for site recognition. AVAILABILITY: The current version of the database is available at http://wwwmgs.bionet.nsc. ru/system/BDNAvideo/. C-code of the recognition program may be found in the section FEATURE. WWW-available programs for testing arbitrary sequences are accessible at http://wwwmgs.bionet.nsc. ru/Programs/bDNA/NA_bDNA.htm/. The links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.

Algorithms↗
PubMedDate not supplied

Oligonucleotide frequency matrices addressed to recognizing functional DNA sites.

MOTIVATION: Recognition of functional sites remains a key event in the course of genomic DNA annotation. It is well known that a number of sites have their own specific oligonucleotide content. This pinpoints the fact that the preference of the site-specific nucleotide combinations at adjacent positions within an analyzed functional site could be informative for this site recognition. Hence, Web-available resources describing the site-specific oligonucleotide content of the functional DNA sites and applying the above approach for site recognition are needed. However, they have been poorly developed up to now. RESULTS: To describe the specific oligonucleotide content of the functional DNA sites, we introduce the oligonucleotide alphabets, out of which the frequency matrix for a given site could be constructed in addition to a traditional nucleotide frequency matrix. Thus, site recognition accuracy increases. This approach was implemented in the activated MATRIX database accumulating oligonucleotide frequency matrices of the functional DNA sites. We have demonstrated that the false-positive error of the functional site recognition decreases if the oligonucleotide frequency matrixes are added to the nucleotide frequency matrixes commonly used. AVAILABILITY: The MATRIX database is available on the Web, http://wwwmgs.bionet.nsc.ru/Dbases/MATRIX/ and the mirror site, http://www.cbil.upenn.edu/mgs/systems/c onsfreq/.

Algorithms↗
PubMedDate not supplied

Conformational and physicochemical DNA features specific for transcription factor binding sites.

MOTIVATION: A reliable recognition of transcription factor binding sites is essential for analysis of regulatory genomic sequences. The experimental data make evident an important role of DNA conformational features for site functioning. However, Internet-available tools for revealing conformational and physicochemical DNA features significant for the site functioning and subsequent use of these features for site recognition have not been developed up to now. RESULTS: We suggest an approach for revealing significant conformational and physicochemical properties of functional sites implemented in the database B-DNA-VIDEO. This database is designed to study the sets of various transcription factor binding sites, providing evidence that transcription factor binding sites are characterized by specific sets of significant conformational and physicochemical DNA properties. For a fixed site, by using the B-DNA features selected for this site recognition, the C-program recognizing this site may be generated, control tested and stored in the database B-DNA-VIDEO. Each B-DNA-VIDEO entry links to the Web-applet recognizing the site, whose significant B-DNA features are stored in this entry as the 'site recognition programs'. The pairwise linked entry-applet pairs are compiled within the B-DNA-VIDEO system, which is simultaneously the database and the program tools package applicable immediately for recognizing the sites stored in the database. Indeed, this is the novelty. Hence, B-DNA-VIDEO is the Web resource of both 'searching for static data' and 'active computation' type, that is why it was called an 'activated database'. AVAILABILITY: B-DNA-VIDEO is available at http://wwwmgs.bionet.nsc.ru/systems/BDNAVideo/ and the mirror site at http://www.cbil.upenn.edu/mgs/systems/c onsfreq/.

Base Sequence↗
PubMedDate not supplied

Integrated databases and computer systems for studying eukaryotic gene expression.

MOTIVATION: The goal of the work was to develop a WWW-oriented computer system providing a maximal integration of informational and software resources on the regulation of gene expression and navigation through them. Rapid growth of the variety and volume of information accumulated in the databases on regulation of gene expression necessarily requires the development of computer systems for automated discovery of the knowledge that can be further used for analysis of regulatory genomic sequences. RESULTS: The GeneExpress system developed includes the following major informational and software modules: (1) Transcription Regulation (TRRD) module, which contains the databases on transcription regulatory regions of eukaryotic genes and TRRD Viewer for data visualization; (2) Site Activity Prediction (ACTIVITY), the module for analysis of functional site activity and its prediction; (3) Site Recognition module, which comprises (a) B-DNA-VIDEO system for detecting the conformational and physicochemical properties of DNA sites significant for their recognition, (b) Consensus and Weight Matrices (ConsFrec) and (c) Transcription Factor Binding Sites Recognition (TFBSR) systems for detecting conservative contextual regions of functional sites and their recognition; (4) Gene Networks (GeneNet), which contains an object-oriented database accumulating the data on gene networks and signal transduction pathways, and the Java-based Viewer for exploration and visualization of the GeneNet information; (5) mRNA Translation (Leader mRNA), designed to analyze structural and contextual properties of mRNA 5'-untranslated regions (5'-UTRs) and predict their translation efficiency; (6) other program modules designed to study the structure-function organization of regulatory genomic sequences and regulatory proteins. AVAILABILITY: GeneExpress is available at http://wwwmgs.bionet.nsc. ru/systems/GeneExpress/ and the links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.

Algorithms↗
PubMedDate not supplied

Identification of sequence-dependent DNA features correlating to activity of DNA sites interacting with proteins.

MOTIVATION: The commonly accepted statistical mechanical theory is now multiply confirmed by using the weight matrix methods successfully recognizing DNA sites binding regulatory proteins in prokaryotes. Nevertheless, the recent evaluation of weight matrix methods application for transcription factor binding site recognition in eukaryotes has unexpectedly revealed that the matrix scores correlate better to each other than to the activity of DNA sites interacting with proteins. This observation points out that molecular mechanisms of DNA/protein recognition are more complicated in eukaryotes than in prokaryotes. As the extra events in eukaryotes, the following processes may be considered: (i) competition between the proteins and nucleosome core particle for DNA sites binding these proteins and (ii) interaction between two synergetic/antagonist proteins recognizing a composed element compiled from two DNA sites binding these proteins. That is why identification of the sequence-dependent DNA features correlating with affinity magnitudes of DNA sites interacting with a protein can pinpoint the molecular event limiting this protein/DNA recognition machinery. RESULTS: An approach for predicting site activity based on its primary nucleotide sequence has been developed. The approach is realized in the computer system ACTIVITY, containing the databases on site activity and on conformational and physicochemical DNA/RNA parameters. By using the system ACTIVITY, an analysis of some sites was provided and the methods for predicting site activity were constructed. The methods developed are in good agreement with the experimental data. AVAILABILITY: The database ACTIVITY is available at http://wwwmgs.bionet.nsc.ru/systems/Activity/ and the mirror site, http://www.cbil.upenn.edu/mgs/systems/acti vity/.

Algorithms↗
PubMedDate not supplied

Prediction of eukaryotic mRNA translational properties.

MOTIVATION: It is well known that eukaryotic mRNAs are translated at different levels depending on their sequence characteristics. Evaluation of mRNA translatability is of importance in prediction of the gene expression pattern by computer methods and to improve the recognition of mRNAs within cloned nucleotide sequences. It may also be used in biotechnological experiments to optimize the expression of foreign genes in transgenic organisms. RESULTS: The sets of 5' untranslated region characteristics, significantly different between mRNAs encoding abundant and scarce polypeptides, were determined for mammals, dicot plants and monocot plants, and collected in the LEADER_RNA database. Computer tools for the prediction of mRNA translatability are presented. AVAILABILITY: Programs for mRNA translatability prediction are available at http://wwwmgs.bionet.nsc. ru/programs/acts2/mo_mRNA.htm (for monocots), http://wwwmgs.bionet. nsc.ru/programs/acts2/di_mRNA.htm (for dicots) and http://wwwmgs. bionet.nsc.ru/programs/acts2/ma_mRNA.htm (for mammals). The LEADER_RNA database may be accessed at: http://wwwmgs.bionet.nsc. ru/systems/LeaderRNA/.

5' Untranslated Regions↗