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Hepatocellular carcinoma (HCC) has been associated with hepatitis C viral (HCV) infection as a potential risk factor. Nonetheless, the precise genetic regulatory mechanisms triggered by the virus, leading to virus-induced hepatocarcinogenesis, remain unclear. We hypothesized that HCV proteins might modulate the activity of aberrantly methylated HCC genes through regulatory pathways. Virus-host regulatory pathways, interactions between proteins, gene expression, transport, and stability regulation, were reconstructed using the ANDSystem. Gene expression regulation was statistically significant. Gene network analysis identified four out of 70 HCC marker genes whose expression regulation by viral proteins may be associated with HCC: DNA-binding protein inhibitor ID – 1 (ID1), flap endonuclease 1 (FEN1), cyclin-dependent kinase inhibitor 2A (CDKN2A), and telomerase reverse transcriptase (TERT). It suggested the following viral protein effects in HCV/human protein heterocomplexes: HCV NS3(p70) protein activates human STAT3 and NOTC1; NS2-3(p23), NS5B(p68), NS1(E2), and core(p21) activate SETD2; NS5A inhibits SMYD3; and NS3 inhibits CCN2. Interestingly, NS3 and E1(gp32) activate c-Jun when it positively regulates CDKN2A and inhibit it when it represses TERT. The discovered regulatory mechanisms might be key areas of focus for creating medications and preventative therapies to decrease the likelihood of HCC development during HCV infection.

Bacillus strains are ubiquitous in the environment and are widely used in the microbiological industry as valuable enzyme sources, as well as in agriculture to stimulate plant growth. The Bacillus genus comprises several closely related groups of species. The rapid classification of these remains challenging using existing methods. Techniques based on MALDI-TOF MS data analysis hold significant promise for fast and precise microbial strains classification at both the genus and species levels. In previous work, we proposed a geometric approach to Bacillus strain classification based on mass spectra analysis via the centroid method (CM). One limitation of such methods is the noise in MS spectra. In this study, we used a denoising autoencoder (DAE) to improve bacteria classification accuracy under noisy MS spectra conditions. We employed a denoising autoencoder approach to convert noisy MS spectra into latent variables representing molecular patterns in the original MS data, and the Random Forest method to classify bacterial strains by latent variables. Comparison of the DAE-RF with the CM method using the artificially noisy test samples showed that DAE-RF offers higher noise robustness. Hence, the DAE-RF method could be utilized for noise-robust, fast, and neat classification of Bacillus species according to MALDI-TOF MS data.

Crop plant breeding involves selecting and developing new plant varieties with desirable traits such as increased yield, improved disease resistance, and enhanced nutritional value. With the development of high-throughput technologies, such as genomics, transcriptomics, and metabolomics, crop breeding has entered a new era. However, to effectively use these technologies, integration of multi-omics data from different databases is required. Integration of omics data provides a comprehensive understanding of the biological processes underlying plant traits and their interactions. This review highlights the importance of integrating omics databases in crop plant breeding, discusses available omics data and databases, describes integration challenges, and highlights recent developments and potential benefits. Taken together, the integration of omics databases is a critical step towards enhancing crop plant breeding and improving global food security.

The prevalence of comorbid diseases poses a major health issue for millions of people worldwide and an enormous socio-economic burden for society. The molecular mechanisms for the development of comorbidities need to be investigated. For this purpose, a workflow system was developed to aggregate data on biomedical entities from heterogeneous data sources. The process of integrating and merging all data sources of the workflow system was implemented as a semi-automatic pipeline that provides the import, fusion, and analysis of the highly connected biomedical data in a Neo4j database GenCoNet. As a starting point, data on the common comorbid diseases essential hypertension and bronchial asthma was integrated. GenCoNet (https://genconet.kalis-amts.de) is a curated database that provides a better understanding of hereditary bases of comorbidities.

Comorbid states of diseases significantly complicate diagnosis and treatment. Molecular mechanisms of comorbid states of asthma and hypertension are still poorly understood. Prioritization is a way for identifying genes involved in complex phenotypic traits. Existing methods of prioritization consider genetic, expression and evolutionary data, molecular-genetic networks and other. In the case of molecular-genetic networks, as a rule, protein-protein interactions and KEGG networks are used. ANDSystem allows reconstructing associative gene networks, which include more than 20 types of interactions, including protein-protein interactions, expression regulation, transport, catalysis, etc. In this work, a set of genes has been prioritized to find genes potentially involved in asthma and hypertension comorbidity. The prioritization was carried out using well-known methods (ToppGene and Endeavor) and a cross-talk centrality criterion, calculated by analysis of associative gene networks from ANDSystem. The identified genes, including IL1A, CD40LG, STAT3, IL15, FAS, APP, TLR2, C3, IL13 and CXCL10, may be involved in the molecular mechanisms of comorbid asthma/hypertension. An analysis of the dynamics of the frequency of mentioning the most priority genes in scientific publications revealed that the top 100 priority genes are significantly enriched with genes with increased positive dynamics, which may be a positive sign for further studies of these genes.

One of the most common comorbid pathology is asthma and arterial hypertension. For experimental modeling of comorbidity we have used spontaneously hypertensive rats with ovalbumin (OVA)-induced asthma. Rats were randomly divided into three groups: control group, OVA-induced asthma group; OVA-induced asthma + IL10 shRNA interference group. Target gene (IL10) was predicted by ANDSystem. We have demonstrated that RNA-interference of IL10 affected cardiovascular (tested using Millar microcatheter system) as well as respiratory functions (tested using force-oscillation technique, Flexivent) in rats. We have shown that during RNA-interference of IL10 gene in vivo there were changes in both cardiac and lung function parameters. These changes in the cardiovascular parameters can be described as positive. But the more intensive heart workload can lead to exhaust and decompensation of the heart functions. Knockdown of IL10 gene in asthma modeling induces some positive changes in respiratory functions of asthmatic animals such as decreased elastance and increased compliance of the lungs, as well as less pronounced pathomorphological changes in the lung tissue. Thus, we provide the data about experimentally confirmed functionality changes of the target which was in silico predicted to be associated with both asthma and hypertension – in our new experimental model of comorbid pathology.

Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial asthma alone was found to be associated with rs1927914 (TLR4), rs1928298 (intergenic variant), and rs1980616 (SERPINA1); hypertension alone was found to be associated with rs11065987 (intergenic variant); rs2284033 (IL2RB), rs11191582 (NT5C2), and rs11669386 (CARD8); comorbidity between asthma and hypertension was found to be associated with rs1010461 (ANG/RNASE4), rs7038716, rs7026297 (LOC105376244), rs7025144 (intergenic variant), and rs2022318 (intergenic variant). The results suggest that genetic background of comorbidity of asthma and hypertension is different from genetic backgrounds of both diseases manifesting isolated.

Detailed investigation of socially important diseases with modern experimental methods has resulted in the generation of large volume of valuable data. However, analysis and interpretation of this data needs application of efficient computational techniques and systems biology approaches. In particular, the techniques allowing the reconstruction of associative networks of various biological objects and events can be useful. In this publication, the combination of different techniques to create such a network associated with an abstract cell environment is discussed in order to gain insights into the functional as well as spatial interrelationships. It is shown that experimentally gained knowledge enriched with data warehouse content and text mining data can be used for the reconstruction and localization of a cardiovascular disease developing network beginning with MUPP1/MPDZ (multi-PDZ domain protein).