ARGO: a web system for the detection of degenerate motifs and large-scale recognition of eukaryotic promoters

Reliable recognition of the promoters in eukaryotic genomes remains an open issue. This is largely owing to the poor understanding of the features of the structural–functional organization of the eukaryotic promoters essential for their function and recognition. However, it was demonstrated that detection of ensembles of regulatory signals characteristic of specific promoter groups increases the accuracy of promoter recognition and prediction of specific expression features of the queried genes. The ARGO_Motifs package was developed for the detection of sets of region-specific degenerate oligonucleotide motifs in the regulatory regions of the eukaryotic genes. The ARGO_Viewer package was developed for the recognition of tissue-specific gene promoters based on the presence and distribution of oligonucleotide motifs obtained by the ARGO_Motifs program. Analysis and recognition of tissue-specific promoters in five gene samples demonstrated high quality of promoter recognition. The public version of the ARGO system is available at and

Pecularities of immunoglobulin gene structures as a basis for somatic mutation emergence

AbstractUsing the method of contextual analysis, we have studied the collection of somatic mutations in immunoglobulin genes. It has been found that the emergence of somatic mutations can be based on the reparation of complementarity violations in the heteroduplexes corresponding to complementary palindromes or direct repeats of DNA

Combined in silico/in vivo analysis of mechanisms providing for root apical meristem self-organization and maintenance.

Background and aimsThe root apical meristem (RAM) is the plant stem cell niche which provides for the formation and continuous development of the root. Auxin is the main regulator of RAM functioning, and auxin maxima coincide with the sites of RAM initiation and maintenance. Auxin gradients are formed due to local auxin biosynthesis and polar auxin transport. The PIN family of auxin transporters plays a critical role in polar auxin transport, and two mechanisms of auxin maximum formation in the RAM based on PIN-mediated auxin transport have been proposed to date: the reverse fountain and the reflected flow mechanisms.MethodsThe two mechanisms are combined here in in silico studies of auxin distribution in intact roots and roots cut into two pieces in the proximal meristem region. In parallel, corresponding experiments were performed in vivo using DR5::GFP Arabidopsis plants.Key resultsThe reverse fountain and the reflected flow mechanism naturally cooperate for RAM patterning and maintenance in intact root. Regeneration of the RAM in decapitated roots is provided by the reflected flow mechanism. In the excised root tips local auxin biosynthesis either alone or in cooperation with the reverse fountain enables RAM maintenance.ConclusionsThe efficiency of a dual-mechanism model in guiding biological experiments on RAM regeneration and maintenance is demonstrated. The model also allows estimation of the concentrations of auxin and PINs in root cells during development and under various treatments. The dual-mechanism model proposed here can be a powerful tool for the study of several different aspects of auxin function in root

Molecular evolution of the hyperthermophilic archaea of the Pyrococcus genus: analysis of adaptation to different environmental conditions

<p>Abstract</p> <p>Background</p> <p>Prokaryotic microorganisms are able to survive and proliferate in severe environmental conditions. The increasing number of complete sequences of prokaryotic genomes has provided the basis for studying the molecular mechanisms of their adaptation at the genomic level. We apply here a computer-based approach to compare the genomes and proteomes from <it>P. furiosus, P. horikoshii</it>, and <it>P. abyssi </it>to identify features of their molecular evolution related to adaptation strategy to diverse environmental conditions.</p> <p>Results</p> <p>Phylogenetic analysis of rRNA genes from 26 Pyrococcus strains suggested that the divergence of <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>might have occurred from ancestral deep-sea organisms. It was demonstrated that the function of genes that have been subject to positive Darwinian selection is closely related to abiotic and biotic conditions to which archaea managed to become adapted. Divergence of the <it>P. furiosus </it>archaea might have been due to loss of some genes involved in cell motility or signal transduction, and/or to evolution under positive selection of the genes for translation machinery. In the course of <it>P. horikoshii </it>divergence, positive selection was found to operate mainly on the transcription machinery; divergence of <it>P. abyssi </it>was related with positive selection for the genes mainly involved in inorganic ion transport. Analysis of radical amino acid replacement rate in evolving <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>showed that the fixation rate was higher for radical substitutions relative to the volume of amino acid side-chain.</p> <p>Conclusions</p> <p>The current results give due credit to the important role of hydrostatic pressure as a cause of variability in the <it>P. furiosus, P. horikoshii </it>and <it>P. abyssi </it>genomes evolving in different habitats. Nevertheless, adaptation to pressure does not appear to be the sole factor ensuring adaptation to environment. For example, at the stage of the divergence of <it>P. horikoshii </it>and <it>P. abyssi</it>, an essential evolutionary role may be assigned to changes in the trophic chain, namely, acquisition of a consumer status at a high (<it>P. horikoshii</it>) or low level (<it>P. abyssi</it>).</p

Recognition of interferon-inducible sites, promoters, and enhancers

BACKGROUND: Computational analysis of gene regulatory regions is important for prediction of functions of many uncharacterized genes. With this in mind, search of the target genes for interferon (IFN) induction appears of interest. IFNs are multi-functional cytokines. Their effects are immunomodulatory, antiviral, antibacterial, and antitumor. The interaction of the IFNs with their cell surface receptors produces an activation of several transcription factors. Four regulatory factors, ISGF3, STAT1, IRF1, and NF-κB, are essential for the function of the IFN system. The aim of this work is the development of computational approaches for the recognition of DNA binding sites for these factors and computer programs for the prediction of the IFN-inducible regions. RESULTS: We developed computational approaches to the recognition of the binding sites for ISGF3, STAT1, IRF1, and NF-κB. Analysis of the distribution of these binding sites demonstrated that the regions -500 upstream of the transcription start site in IFN-inducible genes are enriched in putative binding sites for these transcription factors. Based on selected combinations of the sites whose frequencies were significantly higher than in the other functional gene groups, we developed methods for the prediction of the IFN-inducible promoters and enhancers. We analyzed 1004 sequences of the IFN-inducible genes compiled using microarray data analyses and also about 10,000 human gene sequences from the EPD and RefSeq databases; 74 of 1,664 human genes annotated in EPD were significantly IFN-inducible. CONCLUSION: Analyses of several control datasets demonstrated that the developed methods have a high accuracy of prediction of the IFN-inducible genes. Application of these methods to several datasets suggested that the number of the IFN-inducible genes is approximately 1500–2000 in the human genome

The impact of supply disruption on the standing order system in the FMCG supply chain

Purpose: The article aims to present the impact of supply disruption on the FMCG supply chain's standing order system. Design/Methodology/Approach: The research methodology used is the inventory control system's indicators with a fixed order quantity and graphic modeling. Findings: The system with a fixed order quantity requires the determination of the average annual demand for a given good and the determination of the ordering point, which is important for the FMCG branch. Practical Implications: Delivering goods in the right place and time plays an important role in the supply chain of movable goods. Maintaining a safe level of inventory ensures an effective and smooth flow of inventories through the supply chain's links. Originality/value: This article demonstrates the system with a fixed order quantity allows you to determine the size of the average annual demand for a given good and the point of ordering. It was indicated when logistic companies should use this method.peer-reviewe

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

BACKGROUND: Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. RESULTS: The compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein-coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). CONCLUSIONS: A compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity