METRICS OF VIRTUAL PROMOTION OF A PRODUCT

An approach to the mathematical description of the criterion for the effectiveness of a new object of research – virtual promotion is presented in thepaper. The emergence of this new object of research is connected, on the one hand, with the classical theory of marketing, and on the other withmodern Internet technologies. Marketing is based on the 4P principle: product, price, location and promotion. Promotion is a component of thisprinciple. But in modern conditions, this phenomenon is changing under the influence of the Internet. Now this 4P component is becoming a fullyvirtual instrument. The traditional scheme of promotion functioning is as follows. A message is created to a potential buyer and the delivery channel ofthis message undergoes a change. It is based on the principle: money – goods – money. While the new sales scheme is described by the scheme: weattract a client, make money on a client, we spend money. In the new scheme, we deal with product knowledge in the form of the so-called semanticcore of web content. Knowledge describes for a potential client how a given product can cover his need for something. Using the logistic principles ofthe transfer of goods, this semantic core is loaded into the specified Internet nodes. That is, virtual promotion is formed as two channels: logistics andmarketing. The first one performs three operations: concentration, formatting and distribution of semantic cores on the Internet. The second managesthis process, forming a virtual promotion map. This map is a graph of Internet nodes. It is required to define such a tree of Internet nodes so that virtualpromotion has maximum efficiency. The paper analyzes modern metrics related to the processes of search engine optimization on the Internet.Unfortunately, these metrics evaluate only statistically after the fact of visiting a web resource or the budget of the Internet site in which theadvertising message about the product was placed. Therefore, based on the conversion metric, a criterion for the effectiveness of virtual promotion wasproposed in the work, which takes into account both the attractiveness of the semantic core and the attractiveness of the Internet site where thesemantic core will be located. The criterion reflects the income that we receive depending on the attractiveness of the semantic kernel and the Internetsite.

IMPLEMENTATION OF THE APPROACH TO ONTOLOGICAL MODELING OF THE MUSICAL SUPERGENRE “METAL”

Background. The relevance of the article is due to the development of modern ontological methods of structuring information and the need to systematize data in many new specific subject areas. Such subject areas include the musical art of the "metal" variety, which is quite common today, but insufficiently studied within the terminology. The subject of the article are ontological models and tools for creating ontological knowledge bases. Objective. The purpose of the paper is to increase the correctness of the semantic search in the knowledge base of the musical supergenre "metal". The scientific problem is the need to improve the terminology in this subject area and build an ontological knowledge model that increases the accuracy of information retrieval for the target audience, compared to the existing relational model implemented on one of the known web resources. Methods. Classification method, generalization method, software optimization methods, analytical method. The way to solve the problem: selection based on the comparative characteristics of the best web resource of the subject area and identifying the shortcomings of its model of knowledge representation, designing an ontological knowledge model and testing its effectiveness. Results. The average SUM for all users is 83.85%, which is a good indicator for ontological knowledge bases. At the same time, a similar method of checking the database of the supergenre "metal" on the basis of the site "Encyclopedia Metallum", which used the classical relational model of database organization, showed much lower results. Thus, the average SUM for 10 users was 75.32%, respectively. Conclusions. The scientific novelty of the obtained results is as follows: For the first time an ontological model (ontology) of the subject area was created: musical supergenre "metal", which showed much higher efficiency of semantic search than the best relational model of this subject area, implemented as a web resource. The developed structure can be used to create ontologies of related musical supergenres with similar terminology. Future research also plans to integrate this ontological knowledge model with applied web-based and desktop applications.

IMPROVEMENT OF SVD ALGORITHM TO INCREASE THE EFFICIENCY OF RECOMMENDATION SYSTEMS

Many existing websites use recommendation systems for their users. They generate various offers for them, for example, similar products or recommend the people registered on this site with similar interests. Such referral mechanisms process vast amounts of information to identify potential user preferences. Recommendation systems are programs that try to determine what users want to find, what might interest them, and recommend it to them. These mechanisms have improved the interaction between the user and the site. Instead of static information, they provide dynamic information that changes: recommendations are generated separately for each user, based on his previous activity on this web resource. Information from other visitors may also be taken into account. The methods of collecting information provided by the Internet have greatly simplified the use of human thought through collaborative filtering. But, on the other hand, the large amount of information complicates the implementation of this possibility. For example, the behavior of some people is quite clearly amenable to modeling, while others behave completely unpredictably. And it is the latter that affect the shift of the results of the recommendation system and reduce its effectiveness. An analysis of Internet resources has shown that most of the recommendation systems do not provide recommendations to users, and the part that does, for example, offers products to the user, selects recommendations manually. Therefore, the task of developing methods for automated generation of recommendations for a limited set of input data is quite relevant. The problems of data sparseness, new user problem, scalability of the widely used SVD algorithm for the development of such recommendation systems are proposed to be eliminated by improving this algorithm by the method of the nearest k-neighbors. This method will allow you to easily segment and cluster system data, which will save system resources.

NUCLEOPHILIC SUBSTITUTION OF NITRO GROUP IN 1-METHYL- 5-NITRO-1,2,4-TRIAZOLE BY DIAMINOGLYOXIME

Изучен процесс взаимодействия 1-метил-5-нитро-1,2,4-триазола с многоцентровым бифункциональным О-нуклеофилом – диаминоглиоксимом. Показано, что исходный субстрат вступает в реакцию SNipso-замещения нитрогруппы с гидроксильными группами О-нуклеофила с образованием биологически активного соединения, объединяющего в единой молекуле фармакофорные фрагменты различного типа – 1,2,4-триазоловые гетероциклы и NH2-группы. Процесс сопровождается конкурентными реакциями образования триазолона и продукта его дальнейшего взаимодействия с исходным субстратом. С помощью веб-ресурса PASS Online осуществлен компьютерный скрининг, показано, что исходный субстрат и продукты реакции могут выступать потенциальными фармацевтическими субстанциями. The reaction between 1-methyl-5-nitro-1,2,4-triazome and a concerted bifunctional О-nucleophile – diaminoglyoxime was explored herein. The starting substrate was shown to engage into the SNipso-substitution of the nitro group by the О-nucleophile hydroxyls to furnish a bioactive compound whose single molecule combines different-type pharmacophoric moieties – 1,2,4-triazole heterocycles and NH2groups. The process came amid competitive reactions to form triazolone and a product from its subsequent reaction with the starting substrate. The PASS Online web-resource was used to perform computer-aided screening, demonstrating that the starting substrate and the reaction products can serve as potential pharmaceutical substances.

PLaBAse: A comprehensive web resource for analyzing the plant growth-promoting potential of plant-associated bacteria

Plant-beneficial microorganisms are gaining importance for sustainable plant production and phytosanitary practices. Yet there is a lack of computational approaches targeting bacterial traits associated with plant growth-promotion (PGP), which hinders the in-silico identification, comparison, and selection of phytostimulatory bacterial strains. To address this problem, we have developed the new web resource PLaBAse (v1.01, http://plabase.informatik.uni-tuebingen.de/pb/plabase.php), which provides a number of services, including (i) a database for screening 5,565 plant-associated bacteria (PLaBA-db), (ii) a tool for predicting plant growth-promoting traits (PGPTs) of single bacterial genomes (PGPT-Pred), and (iii) a tool for the prediction of bacterial plant-association by marker gene identification (PIFAR-Pred). The latter was developed by Martĺnez-Garcĺa et al. and is now hosted at University of Tuebingen. The PGPT-Pred tool is based on our new PGPT ontology, a literature- and OMICs-curated, comprehensive, and hierarchical collection of ~6,900 PGPTs that are associated with 6,965,955 protein sequences. To study the distribution of the PGPTs across different environments, we applied it to 70,540 bacterial strains associated with (i) seven different environments (including plants), (iii) five different plant spheres (organs), and (iii) two bacteria-induced plant phenotypes. This analysis revealed that plant-symbiotic bacteria generally have a larger genome size and a higher count of PGPT-annotated protein encoding genes. Obviously, not all reported PGPTs are restricted to -or only enriched in- plant-associated and plant symbiotic bacteria. Some also occur in human- and animal-associated bacteria, perhaps due to the transmission of PGP bacteria (PGPBs) between environments, or because some functions are involved in adaption processes to various environments. Here we provide an easy-to-use approach for screening of PGPTs in bacterial genomes across various phyla and isolation sites, using PLaBA-db, and for standardized annotation, using PGPT-Pred. We believe that this resource will improve our understanding about the entire PGP processes and facilitate the prediction of PGPB as bio-inoculants and for biosafety strategies, so as to help to establish sustainable and targeted bacteria-incorporated plant production systems in the future.

Sex bias evaluation of classic and novel Housekeeping Genes in adipose tissue through the massive analysis of transcriptomics data

ABSTRACTHousekeeping genes (HKG), those involved in the maintenance of basic cell functions, are considered to have constant expression levels in all cell types, and are therefore commonly used as internal controls in gene expression studies. Nevertheless, multiple studies have shown that not all of them have stable expression levels across different cells, tissues, and conditions, introducing a systematic error in the experimental results. The proper selection and validation of control housekeeping genes in the specific studied conditions is crucial for the validity of the obtained results, although, up to date, sex has never been taken into account as a biological variable.In this work, we evaluate the expression profiles of six classical housekeeping genes, (four metabolic: HPRT, GAPDH, PPIA and UBC, and two ribosomal: 18S and RPL19) used as controls in several tissues, to determine the stability of their expression in adipose tissue of Homo sapiens and Mus musculus and asses sex bias and control suitability. We also evaluated gene expression stability of the genes included in different whole transcriptome microarrays available at the Gene Expression Omnibus database (GEO), to identify new genes suitable to be used as sex-unbiased controls. We perform a sex-based analysis to test for/reveal sexual dimorphism of mRNA expression stability.We use a novel computational strategy based on meta-analysis techniques which evidence that some classical housekeeping genes do not fit to analyze human adipose tissue when sex variable is included. For instance, the extensively used 18S has shown to be variable in this tissue, while PPIA and RPL19 have shown to be good HKG targets. Further, we propose new sex-unbiased human and mouse housekeeping genes, derived from sex-specific expression profiles, including, RPS8 or UBB. All the results generated in this work are available in an open web resource (https://bioinfo.cipf.es/metafun-HKG), so that they can be consulted and used in further studies.

U-CIE [/juː ’siː/]: Color encoding of high-dimensional data

U-CIE is a visualization method that encodes arbitrary high-dimensional data as colors using a combination of dimensionality reduction and the CIELAB color space to retain the original structure to the extent possible. We illustrate its broad applicability by visualizing single-cell data on a protein network and metagenomic data on a world map and on scatter plots. U-CIE is available as a web resource at https://u-cie.jensenlab.org/ and as an R package.

Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression

Comprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes the roadmap to tumor progression in a qualitative and quantitative manner. Most cancers follow a uniform trajectory characterized by upregulation of polycomb-repressive-complex-2, G2-M checkpoints, and M2 macrophage polarization. Using patient-derived xenograft models, we functionally validate our observations and add single-cell resolution. Thereby, we show that tumor progression occurs through transcriptional adaption rather than a selection of pre-existing cancer cell clusters. Moreover, we determine at the single-cell level how inhibition of EZH2 - the top upregulated gene along the trajectory – reverts tumor progression and macrophage polarization. Finally, a user-friendly web-resource is provided enabling the investigation of dynamic transcriptional perturbations linked to disease progression.

Circular RNA signatures of human healing and non-healing wounds

Background: Although the widespread expression of circular RNAs (circRNAs) has only been recognized recently, increasing evidence has suggested their important roles in health and disease. To identify clinically relevant circRNAs with potential for wound diagnosis and therapy, an in-depth characterization of circRNA expression in human healing and non-healing wounds is a prerequisite that has not been attained yet. Methods: We collected wound-edge biopsies through the healing process of healthy donors and in chronic non-healing venous ulcers (VU). Paired total RNA- and small RNA-sequencing were performed to profile circRNAs, protein-coding mRNAs, and microRNA expression. We analyzed the co-expression relationship between circRNAs and mRNAs with weighted correlation network analysis (WGCNA) and constructed circRNA-microRNA-mRNA networks. For the circRNAs surfaced in the in-silico analysis, after validating their expression with RT-PCR and sequencing, we silenced hsa-CHST15_0003 and hsa-TNFRSF21_0001 expression in keratinocytes with siRNAs and studied their function with transcriptomic profiling and live-cell monitoring. Results: Our study unravels the dynamically changed expression patterns of circRNAs during human skin wound healing and their abnormal expression signature in VU, which are presented as a searchable web resource (http://130.229.28.87/shiny/circRNA_wholebiopsy-shinyApp/). In silico analysis deciphers the circRNA-miRNAs-mRNA networks specific to the inflammatory and proliferative phases of wound repair and VU, the biological processes that circRNAs are involved, and the circRNAs that could act as miRNAs sponge in human wounds. Importantly, we found that hsa-CHST15_0003 and hsa-TNFRSF21_0001, two circRNAs upregulated in VU, hampered keratinocyte migration while promoting proliferation through modulating gene networks underpinning these cellular processes. Conclusion: By integrating circRNA, mRNA, and miRNA expression profiles in a unique collection of clinical samples, we identify the circRNAs that are relevant to human wound healing physiology and pathology. This study paves the way to decipher the functional significance of circRNAs in tissue repair.

cSurvival: a web resource for biomarker interactions in cancer outcomes

Survival analysis is a technique to identify prognostic biomarkers and genetic vulnerabilities in cancer studies. Large-scale consortium-based projects have profiled >11,000 adult and >4,000 paediatric tumor cases with clinical outcomes and multi-omics approaches. This provides a resource for investigating molecular-level cancer etiologies using clinical correlations. Although cancers often arise from multiple genetic vulnerabilities and have deregulated gene sets (GSs), existing survival analysis protocols can report only on individual genes. Additionally, there is no systematic method to connect clinical outcomes with experimental (cell line) data. To address these gaps, we developed cSurvival (https://tau.cmmt.ubc.ca/cSurvival). cSurvival provides a user-adjustable analytical pipeline with a curated, integrated database, and offers three main advances: (a) joint analysis with two genomic predictors to identify interacting biomarkers, including new algorithms to identify optimal cutoffs for two continuous predictors; (b) survival analysis not only at the gene, but also the GS level; and (c) integration of clinical and experimental cell line studies to generate synergistic biological insights. To demonstrate these advances, we report three case studies. We confirmed findings of autophagy-dependent survival in colorectal cancers and of synergistic negative effects between high expression of SLC7A11 and SLC2A1 on outcomes in several cancers. We further used cSurvival to identify high expression of the Nrf2-antioxidant response element pathway as a main indicator for lung cancer prognosis and for cellular resistance to oxidative stress-inducing drugs. Together, these analyses demonstrate cSurvival's ability to support biomarker prognosis and interaction analysis via gene- and GS-level approaches and to integrate clinical and experimental biomedical studies.