Delay-differential SEIR modeling for improved modelling of infection dynamics.

SEIR (Susceptible-Exposed-Infected-Recovered) approach is a classic modeling method that is frequently used to study infectious diseases. However, in the vast majority of such models transitions from one population group to another are described using the mass-action law. That causes inability to reproduce observable dynamics of an infection such as the incubation period or progression of the disease's symptoms. In this paper, we propose a new approach to simulate the epidemic dynamics based on a system of differential equations with time delays and instant transitions to approximate durations of transition processes more correctly and make model parameters more clear. The suggested approach can be applied not only to Covid-19 but also to the study of other infectious diseases. We utilized it in the development of the delay-based model of the COVID-19 pandemic in Germany and France. The model takes into account testing of different population groups, symptoms progression from mild to critical, vaccination, duration of protective immunity and new virus strains. The stringency index was used as a generalized characteristic of the non-pharmaceutical government interventions in corresponding countries to contain the virus spread. The parameter identifiability analysis demonstrated that the presented modeling approach enables to significantly reduce the number of parameters and make them more identifiable. Both models are publicly available.

[Air pollution by particulate matter as the risk factor for the cardiovascular diseases].

In the review there highlighted contemporary concepts about the relation between the air pollution by the particulate matter (PM) and human morbidity and mortality rate due to cardiovascular diseases. There are considered results of the short- and long-term PM impact on the human cardiovascular system in the dependence on size, origin, chemical composition, and concentration in the air. Authors performed the formalized description of the action and possible effects of PM on vascular endothelium presented as an example of systemization. Summarizing data respective knowledge collected in the literature were used in the article as an example.

[Prediction of a non-small cell lung cancer sensitivity to cisplatin and paclitaxel based on the marker genes expression].

The goal of the present study was to define gene expression signatures that predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate set of candidate genes likely to be predictive a current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty four genes coding proteins belonging to following categories: ATP-dependent transport proteins, detoxification system proteins, reparation system proteins, tubulin and proteins responsible for its synthesis, cell cycle and apoptosis proteins were considered. Eight NSCLC cell lines (A549, Calul, H1299, H322, H358, H460, H292, and H23) were used in our study. For each NSCLC cell line a cisplatin and paclitaxel chemosensitivity as well as an expression level of 44 candidate genes were evaluated. To develop a chemosensitivity prediction model based on selected genes expression level a multiple regression analysis was performed. The model based on the expression level of 11 genes (TUBB3, TXR1, MRP5, MSH2, ERCC1, STMN, SMAC, FOLR1, PTPN14, HSPA2, GSTP1) allowed us to predict the paclitaxel cytotoxic concentration with high level of correlation (r = 0.91, p < 0.01). However, none model developed was able to reliably predict a sensitivity of the NSCLC cells to cisplatin.

Transcription regulatory regions database (TRRD): its status in 2000.

Transcription Regulatory Regions Database (TRRD) has been developed for accumulation of experimental information on the structure-function features of regulatory regions of eukaryotic genes. Each entry in TRRD corresponds to a particular gene and contains a description of structure-function features of its regulatory regions (transcription factor binding sites, promoters, enhancers, silencers, etc.) and gene expression regulation patterns. The current release, TRRD 4.2.5, comprises the description of 760 genes, 3403 expression patterns, and >4600 regulatory elements including 3604 transcription factor binding sites, 600 promoters and 152 enhancers. This information was obtained through annotation of 2537 scientific publications. TRRD 4.2.5 is available through the WWW at http://wwwmgs.bionet.nsc.ru/mgs/dbases/trrd4/

[Automatic generation of gene network schemes based on their formalized description in the GeneNet database]. / Avtomaticheskaia generatsiia skhem gennykh setei na osnove ikh formalizovannogo opisaniia v baze dannykh GeneNet.

A database for gene networks GeneNet was created. The main principles of formalized description of gene networks for the cases of regulation of antiviral responses and hemopoiesis were developed. A program for automatic graphical representation of diagrams of gene networks was created, which is based on their formalized description. A system of filters was developed, which makes it possible to select individual network components for graphical representation. The selection can be performed with respect to specific type of treatment, species, and/or cell type. The GeneNet database is accessible via Internet at http://wwwmgs.bionet.nsc.ru/systems/MGL/Gen eNet.

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+ ++.

Interactive data input into the GeneNet database.

SUMMARY: The GeneNet database has been developed for a formalized hierarchical description of the gene networks. To provide rapid data accumulation in the database, the Java graphical interface for data input through the Internet by independent experts equipped with convenient visual tools is developed. AVAILABILITY: http://wwwmgs. bionet.nsc.ru/systems/MGL/GeneNet/

Transcription Regulatory Regions Database (TRRD):its status in 1999.

The Transcription Regulatory Regions Database (TRRD) is a curated database designed for accumulation of experimental data on extended regulatory regions of eukaryotic genes, the regulatory elements they contain, i.e., transcription factor binding sites, promoters, enhancers, silencers, etc., and expression patterns of the genes. Release 4.1 of TRRD offers a number of significant improvements, in particular, a more detailed description of transcription factor binding sites, transcription factors per se, and gene expression patterns in a computer-readable format. In addition, the new TRRD release provides considerably more references to other molecular biological databases. TRRD 4.1 is installed under SRS and is available through the WWW at http://www.bionet.nsc.ru/trrd/

[GeneExpress: an integrator for databases and computer systems accessible by the Internet and intended for studying eukaryotic gene expression]. / Gene Express: integrator baz dannykh i komp'iuternykh sistem, dostupnykh po seti internet i prednaznachennykh dlia izucheniia ékspresii genov éukariot.

We have developed GeneExpress that is the WWW-oriented integrator for the databases and systems supporting the investigation of gene expression. The total number of the Web-based resources integrated is 30. The database GeneNet on molecular events forming gene networks was assigned its integrative core. To navigate all these WWW-available resources, the SRS, HTML, and Java viewers were developed, http:@wwwmgs.bionet.nsc.ru/systems/GeneExpress/.

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.

GeneNet: a gene network database and its automated visualization.

MOTIVATION: Gene networks that provide the regulation of physiological processes are the basic feature of organisms. Information regarding the regulation of gene expression and signal transduction pathways is increasing rapidly. However, the information is hard to formalize and systematize. Ways and means for automated visualization of the gene networks based on their formalized description are needed. RESULTS: The object-oriented database GeneNet and the software for its automated visualization have been developed. The main principles of a formalized description of the gene network have been worked out. Antiviral response and erythropoiesis are provided as examples to show how this is achieved. The GeneNet graphical user interface written in Java provides automated generation of the gene network diagrams and allows visualization and exploration of the GeneNet database through the Internet. A system of filters allows the selection of particular components of the network for visualization. AVAILABILITY: The GeneNet database and its graphical user interface are available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneN et/ CONTACT: fedor@bionet.nsc.ru

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