Reconstruction and analysis of the gene regulatory network for cell wall function in Arabidopsis thaliana L. leaves in response to water deficit.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit. The adaptation mechanisms of the cell wall to water loss are of interest for identifying important genetic factors determining plant drought resistance and provide valuable information on biomarkers for further selection aimed at increasing the yield of crop plants. Using ANDSystem, a gene network describing the regulation of CWPs under water restriction conditions was reconstructed. The analysis of the gene network and the transcriptome data analysis allowed prioritizing transcription factors (TF) based on their enrichment of differentially expressed genes regulated by them. As a result, scores were calculated, acting as indicators of the association of TFs with water deficit. On the basis of the score values, eight most significant TFs were selected. The highest priority was given to the TF GBF3. CWPs were prioritized according to the criterion of summing up the scores of transcription factors regulating these genes. Among the most prioritized CWPs were the AT5G03350 gene encoding a lectin-like protein, AT4G20860 encoding BBE-like 22 required for the oxidation of cellulose degradation products, and AT4G37800 encoding xyloglucan endotransglucosylase/ hydrolase 7. Overall, the implemented algorithm could be used for prediction of regulatory interactions between transcription factors and target genes encoding cell wall proteins in plants.

[N-aсetyltransferase (NAT2) gene polymorphism and gene network analysis]. / Polimorfizm variantov gena N-atsetiltransferazy 2 (NAT2) i analiz gennoi seti.

To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.

[Reconstruction of gene network associated with Parkinson disease for gene targets search]. / Rekonstruktsiia gennoi seti bolezni Parkinsona dlia poiska genov-mishenei.

Accumulation of genetic data in the field of Parkinson's disease research culminated in identifying risk factors and confident prediction of the disease occurrence. To find new gene-targets for diagnostics and therapy we have to reconstruct gene network of the disease, to cluster genes in the network, to reveal key (hub) genes with largest number of interactions in the network. Using the on-line bioinformatics tools OMIM, PANTHER, g:Profiler, GeneMANIA, and STRING-DB, we have analyzed the current array of data related to Parkinson's disease, calculated the categories of gene ontologies for a large list of genes, visualized them, and built gene networks containing the identified key objects and their relationships. However, translating the results into biological understanding is still a promising major challenge. The analysis of the genes associated with the disease, the assessment of their place in the gene network (connectivity) allows us to evaluate them as target genes for medicinal effects.

[Differential alternative splicing in brain regions of rats selected for aggressive behavior].

Profiles of alternative mRNA isoforms have been determined in three brain regions of rats from an aggressive and a tame line selected for 74 generations. Among 2319 genes with alternatively spliced exons, approximately 84% were confirmed by analyzing public databases. Based on Gene Ontology-guided clustering of alternatively spliced genes, it has been found that the sample was enriched in synapse-specific genes (FDR < 10^(-17)). Patterns of gene expression in the brains of animals with genetically determined high or low aggression were more frequently found to differ in the use of alternatively spliced exons than in animals environmentally conditioned for increased or lowered propensity to aggression. For the Adcyap1r1 gene, five alternatively spliced mRNA isoforms have been represented differentially in aggressive animals. A detailed analysis of the gene that encodes glutamate ionotropic receptor NMDA type subunit 1 (Grin1) has confirmed significant differences in the levels of its alternatively spliced isoforms in certain brain regions of tame and aggressive rats. These differences may affect the behavior in rats genetically selected for aggression levels.

[Computer methods of analysis of chromosome contacts in the cell nucleus based on sequencing technology data]. / Komp'iuternye metody analiza khromosomnykh kontaktov v iadre kletki po dannym tekhnologii sekvenirovaniia.

The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research. The technique of chromatin immunoprecipitation and subsequent sequencing (ChIP-seq) make possible to determine binding sites of transcription factors that regulate expression of eukaryotic genes; genome transcription factors binding maps have been. The ChIA-PET technology allows exploring not only target protein binding sites, but also pairs of such sites on proximally located and interacting with each other chromosomes co-located in three-dimensional space of the cell nucleus. Here we discuss the principles of the construction of genomic maps and matrices of chromosome contacts according to ChIA-PET and Hi-C data that capture the chromosome conformation and overview existing software for 3D genome analysis including in house programs of gene location analysis in topological domains.

Transcription factors for the modulation of pluripotency and reprogramming.

Pluripotency and self-renewal are the defining traits of embryonic stem cells (ESCs) and this status quo is maintained by the core transcription factors Oct4, Sox2, and Nanog. Genome-wide mapping of the binding sites of these pivotal factors and other ESC transcriptional regulators has unraveled the transcriptional network governing pluripotency. Strikingly, a sizeable fraction of the binding sites of Oct4 and Nanog are not conserved in mouse and human ESCs. Binding site turnover and the presence of species-specific transposable elements are some of the factors contributing to this disp arity. Hence, comparing human and mouse ESCs will shed new light on the design of transcriptional regulatory networks for pluripotency. Despite the significant differences among pluripotent mammalian stem cells, the same set of transcription factors (Oct4, Sox2, Klf4, and c-Myc) can be used to reprogram human and mouse somatic cells into induced pluripotent stem cells. Recent works also demonstrate that there are multiple ways of imparting pluripotency. For instance, the nuclear receptors Nr5a2 and Esrrb can, respectively, substitute for Oct4 and Klf4 in reprogramming. This chapter summarizes the different roles of transcription factors in the modulation of pluripotent states and in the induction of pluripotent phenotypes.

Complexity: an internet resource for analysis of DNA sequence complexity.

The search for DNA regions with low complexity is one of the pivotal tasks of modern structural analysis of complete genomes. The low complexity may be preconditioned by strong inequality in nucleotide content (biased composition), by tandem or dispersed repeats or by palindrome-hairpin structures, as well as by a combination of all these factors. Several numerical measures of textual complexity, including combinatorial and linguistic ones, together with complexity estimation using a modified Lempel-Ziv algorithm, have been implemented in a software tool called 'Complexity' (http://wwwmgs.bionet.nsc.ru/mgs/programs/low_complexity/). The software enables a user to search for low-complexity regions in long sequences, e.g. complete bacterial genomes or eukaryotic chromosomes. In addition, it estimates the complexity of groups of aligned sequences.