Nikolay L. Podkolodny

Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL

TRANSFAC, TRRD (Transcription Regulatory Region Database) and COMPEL are databases which store information about transcriptional regulation in eukaryotic cells. The three databases provide distinct views on the components involved in transcription: transcription factors and their binding sites and binding profiles (TRANSFAC), the regulatory hierarchy of whole genes (TRRD), and the structural and functional properties of composite elements (COMPEL). The quantitative and qualitative changes of all three databases and connected programs are described. The databases are accessible via WWW:http://transfac.gbf.de/TRANSFAC orhttp://www.bionet.nsc.ru/TRRD

Transcription Regulatory Regions Database (TRRD): its status in 2002

Transcription Regulatory Regions Database (TRRD) is an informational resource containing an integrated description of the gene transcription regulation. An entry of the database corresponds to a gene and contains the data on localization and functions of the transcription regulatory regions as well as gene expression patterns. TRRD contains only experimental data that are inputted into the database through annotating scientific publication. TRRD release 6.0 comprises the information on 1167 genes, 5537 transcription factor binding sites, 1714 regulatory regions, 14 locus control regions and 5335 expression patterns obtained through annotating 3898 scientific papers. This information is arranged in seven databases: TRRDGENES (general gene description), TRRDLCR (locus control regions); TRRDUNITS (regulatory regions: promoters, enhancers, silencers, etc.), TRRDSITES (transcription factor binding sites), TRRDFACTORS (transcription factors), TRRDEXP (expression patterns) and TRRDBIB (experimental publications). Sequence Retrieval System (SRS) is used as a basic tool for navigating and searching TRRD and integrating it with external informational and software resources. The visualization tool, TRRD Viewer, provides the information representation in a form of maps of gene regulatory regions. The option allowing nucleotide sequences to be searched for according to their homology using BLAST is also included. TRRD is available at http://www.bionet.nsc.ru/trrd/.

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/.

GeneNet in 2005

The GeneNet system is designed for collection and analysis of the data on gene and metabolic networks, signal transduction pathways and kinetic characteristics of elementary processes. In the past 2 years, the GeneNet structure was considerably improved: (i) the current version of the database is now implemented using ORACLE9i; (ii) the capacities to describe the structure of the protein complexes and the interactions between the units are increased; (iii) two tables with kinetic constants and more detailed descriptions of certain reactions were added; and (iv) a module for kinetic modeling was supplemented. The current SRS release of the GeneNet database contains 37 graphical maps of gene networks, as well as descriptions of 1766 proteins, 1006 genes, 241 small molecules and 3254 relationships between gene network units, and 552 kinetic constants. Information distributed between 16 interlinked tables was obtained by annotating 1980 journal publications. SRS release of the GeneNet database, the graphical viewer and the modeling section are available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/.

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/.

GeneNet: a database on structure and functional organisation of gene networks.

The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 proteins, 567 genes, 151 other substances and 1364 relationships between components of gene networks. Information distributed between 14 interlinked tables was obtained by annotating 968 scientific publications. The SRS-version of GeneNet database is freely available (http://wwwmgs.bionet.nsc.ru/mgs/systems/genenet/).

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

Transcription Regulatory Regions Database (TRRD): A Source of Experimentally Confirmed Data on Transcription Regulatory Regions of Eukaryotic Genes

The goal of creation of the Transcription Regulatory Regions Database (TRRD) was to provide a complete and adequate description of the structure-function organization of transcription regulatory regions in eukaryotic genes. TRRD contains only experimentally confirmed data about (i) transcription factor binding sites; (ii) regulatory units (promoter regions, enhancers, and silencers); and (iii) locus control regions. The main tool for searching TRRD and navigation in it is SRS. TRRD has hierarchically organized vocabularies and thesauruses used for developing specialized data retrieval tools. The current TRRD release contains information about 2308 eukaryotic genes (of them, 34 % are human genes) inputted basing on annotation of 7565 scientific papers. For these genes, the largest in the world sets of experimentally confirmed regulatory units (3439) and transcription factor binding sites (10 045) are collected in TRRD. Of them, 37 % of regulatory units and 38 % of binding sites are related to human genes. This paper characterizes groups of experiments basing on which regulatory units and binding sites are annotated. Examples of TRRD entries are given. The database is available at http://www.bionet.nsc.ru/trrd/.

An Integrated Computer System for Studying the Regulation of Eukaryotic Gene Expression

The review describes several modules of the GeneExpress integrated computer system concerning the regulation of gene expression in eukaryotes. Approaches to the presentation of experimental data in databases are considered. The employment of GeneExpress in computer analysis and modeling of the organization and function of genetic systems is illustrated with examples. GeneExpress is available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/.

From published expression and phenotype data to structured knowledge: the arabidopsis gene net supplementary database and its applications

We report on the development progress of the AGNS (Arabidopsis gene net supplementary) database and a AGNS-based information system for automation of research on the morphogenesis of Arabidopsis thaliana (L.), a well-known model plant in system biology.