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1.
J Integr Bioinform ; 20(3)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37978846

RESUMEN

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.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Virosis , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatitis C/complicaciones , Hepatitis C/genética , N-Metiltransferasa de Histona-Lisina
2.
J Integr Bioinform ; 20(3)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37978847

RESUMEN

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.


Asunto(s)
Bacillus , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Bacterias
3.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36499269

RESUMEN

The body of scientific literature continues to grow annually. Over 1.5 million abstracts of biomedical publications were added to the PubMed database in 2021. Therefore, developing cognitive systems that provide a specialized search for information in scientific publications based on subject area ontology and modern artificial intelligence methods is urgently needed. We previously developed a web-based information retrieval system, ANDDigest, designed to search and analyze information in the PubMed database using a customized domain ontology. This paper presents an improved ANDDigest version that uses fine-tuned PubMedBERT classifiers to enhance the quality of short name recognition for molecular-genetics entities in PubMed abstracts on eight biological object types: cell components, diseases, side effects, genes, proteins, pathways, drugs, and metabolites. This approach increased average short name recognition accuracy by 13%.


Asunto(s)
Inteligencia Artificial , Minería de Datos , Minería de Datos/métodos , PubMed , Bases de Datos Factuales , Proteínas
4.
BMC Microbiol ; 20(Suppl 2): 349, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33228530

RESUMEN

BACKGROUND: The Uzon Caldera is one of the places on our planet with unique geological, ecological, and microbiological characteristics. Uzon oil is the youngest on Earth. Uzon oil has unique composition, with low proportion of heavy fractions and relatively high content of saturated hydrocarbons. Microbial communities of the «oil site¼ have a diverse composition and live at high temperatures (up to 97 °C), significant oscillations of Eh and pH, and high content of sulfur, sulfides, arsenic, antimony, and mercury in water and rocks. RESULTS: The study analyzed the composition, structure and unique genetics characteristics of the microbial communities of the oil site, analyzed the metabolic pathways in the communities. Metabolic pathways of hydrocarbon degradation by microorganisms have been found. The study found statistically significant relationships between geochemical parameters, taxonomic composition and the completeness of metabolic pathways. It was demonstrated that geochemical parameters determine the structure and metabolic potential of microbial communities. CONCLUSIONS: There were statistically significant relationships between geochemical parameters, taxonomic composition, and the completeness of metabolic pathways. It was demonstrated that geochemical parameters define the structure and metabolic potential of microbial communities. Metabolic pathways of hydrocarbon oxidation was found to prevail in the studied communities, which corroborates the hypothesis on abiogenic synthesis of Uzon hydrothermal petroleum.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Manantiales de Aguas Termales/microbiología , Hidrocarburos/metabolismo , Suelo/química , Archaea/genética , Archaea/aislamiento & purificación , Bacterias/genética , Bacterias/aislamiento & purificación , Biodegradación Ambiental , ADN Ribosómico/genética , Manantiales de Aguas Termales/química , Concentración de Iones de Hidrógeno , Redes y Vías Metabólicas , Microbiota , Filogenia , ARN Ribosómico 16S/genética
5.
BMC Bioinformatics ; 21(Suppl 11): 228, 2020 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-32921303

RESUMEN

BACKGROUND: The rapid growth of scientific literature has rendered the task of finding relevant information one of the critical problems in almost any research. Search engines, like Google Scholar, Web of Knowledge, PubMed, Scopus, and others, are highly effective in document search; however, they do not allow knowledge extraction. In contrast to the search engines, text-mining systems provide extraction of knowledge with representations in the form of semantic networks. Of particular interest are tools performing a full cycle of knowledge management and engineering, including automated retrieval, integration, and representation of knowledge in the form of semantic networks, their visualization, and analysis. STRING, Pathway Studio, MetaCore, and others are well-known examples of such products. Previously, we developed the Associative Network Discovery System (ANDSystem), which also implements such a cycle. However, the drawback of these systems is dependence on the employed ontologies describing the subject area, which limits their functionality in searching information based on user-specified queries. RESULTS: The ANDDigest system is a new web-based module of the ANDSystem tool, permitting searching within PubMed by using dictionaries from the ANDSystem tool and sets of user-defined keywords. ANDDigest allows performing the search based on complex queries simultaneously, taking into account many types of objects from the ANDSystem's ontology. The system has a user-friendly interface, providing sorting, visualization, and filtering of the found information, including mapping of mentioned objects in text, linking to external databases, sorting of data by publication date, citations number, journal H-indices, etc. The system provides data on trends for identified entities based on dynamics of interest according to the frequency of their mentions in PubMed by years. CONCLUSIONS: The main feature of ANDDigest is its functionality, serving as a specialized search for information about multiple associative relationships of objects from the ANDSystem's ontology vocabularies, taking into account user-specified keywords. The tool can be applied to the interpretation of experimental genetics data, the search for associations between molecular genetics objects, and the preparation of scientific and analytical reviews. It is presently available at https://anddigest.sysbio.ru/ .


Asunto(s)
Minería de Datos/métodos , Internet , Programas Informáticos , Bases de Datos Factuales , PubMed
6.
Methods Mol Biol ; 1934: 1-20, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31256369

RESUMEN

The increase in the number of Web-based resources on posttranslational modification sites (PTMSs) in proteins is accelerating. This chapter presents a set of computational protocols describing how to work with the Internet resources when dealing with PTMSs. The protocols are intended for querying in PTMS-related databases, search of the PTMSs in the protein sequences and structures, and calculating the pI and molecular mass of the PTM isoforms. Thus, the modern bioinformatics prediction tools make it feasible to express protein modification in broader quantitative terms.


Asunto(s)
Biología Computacional/métodos , Internet , Procesamiento Proteico-Postraduccional , Proteínas , Programas Informáticos , Secuencia de Aminoácidos , Bases de Datos de Proteínas , Peso Molecular , Proteínas/química , Proteínas/metabolismo , Motor de Búsqueda , Interfaz Usuario-Computador , Navegador Web
7.
BMC Med Genomics ; 12(Suppl 2): 47, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30871556

RESUMEN

BACKGROUND: Currently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. METHODS: In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. RESULTS: An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema. CONCLUSIONS: Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.


Asunto(s)
Apoptosis , Redes Reguladoras de Genes , Linfedema/patología , Programas Informáticos , Animales , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Quimiocina CCL2/genética , Bases de Datos Genéticas , Modelos Animales de Enfermedad , Células Endoteliales/citología , Células Endoteliales/metabolismo , Linfedema/genética , Ratones , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética
8.
BMC Bioinformatics ; 20(Suppl 1): 34, 2019 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-30717676

RESUMEN

BACKGROUND: Consideration of tissue-specific gene expression in reconstruction and analysis of molecular genetic networks is necessary for a proper description of the processes occurring in a specified tissue. Currently, there are a number of computer systems that allow the user to reconstruct molecular-genetic networks using the data automatically extracted from the texts of scientific publications. Examples of such systems are STRING, Pathway Commons, MetaCore and Ingenuity. The MetaCore and Ingenuity systems permit taking into account tissue-specific gene expression during the reconstruction of gene networks. Previously, we developed the ANDSystem tool, which also provides an automated extraction of knowledge from scientific texts and allows the reconstruction of gene networks. The main difference between our system and other tools is in the different types of interactions between objects, which makes the ANDSystem complementary to existing well-known systems. However, previous versions of the ANDSystem did not contain any information on tissue-specific expression. RESULTS: A new version of the ANDSystem has been developed. It offers the reconstruction of associative gene networks while taking into account the tissue-specific gene expression. The ANDSystem knowledge base features information on tissue-specific expression for 272 tissues. The system allows the reconstruction of combined gene networks, as well as performing the filtering of genes from such networks using the information on their tissue-specific expression. As an example of the application of such filtering, the gene network of the extrinsic apoptotic signaling pathway was analyzed. It was shown that considering different tissues can lead to changes in gene network structure, including changes in such indicators as betweenness centrality of vertices, clustering coefficient, network centralization, network density, etc. CONCLUSIONS: The consideration of tissue specificity can play an important role in the analysis of gene networks, in particular solving the problem of finding the most significant central genes. Thus, the new version of ANDSystem can be employed for a wide range of tasks related to biomedical studies of individual tissues. It is available at http://www-bionet.sscc.ru/and/cell /.


Asunto(s)
Minería de Datos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Especificidad de Órganos/genética , Publicaciones , Apoptosis/genética , Humanos , Semántica , Transducción de Señal/genética
9.
BMC Genomics ; 19(Suppl 3): 76, 2018 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-29504895

RESUMEN

BACKGROUND: Estimation of functional connectivity in gene sets derived from genome-wide or other biological experiments is one of the essential tasks of bioinformatics. A promising approach for solving this problem is to compare gene networks built using experimental gene sets with random networks. One of the resources that make such an analysis possible is CrossTalkZ, which uses the FunCoup database. However, existing methods, including CrossTalkZ, do not take into account individual types of interactions, such as protein/protein interactions, expression regulation, transport regulation, catalytic reactions, etc., but rather work with generalized types characterizing the existence of any connection between network members. RESULTS: We developed the online tool FunGeneNet, which utilizes the ANDSystem and STRING to reconstruct gene networks using experimental gene sets and to estimate their difference from random networks. To compare the reconstructed networks with random ones, the node permutation algorithm implemented in CrossTalkZ was taken as a basis. To study the FunGeneNet applicability, the functional connectivity analysis of networks constructed for gene sets involved in the Gene Ontology biological processes was conducted. We showed that the method sensitivity exceeds 0.8 at a specificity of 0.95. We found that the significance level of the difference between gene networks of biological processes and random networks is determined by the type of connections considered between objects. At the same time, the highest reliability is achieved for the generalized form of connections that takes into account all the individual types of connections. By taking examples of the thyroid cancer networks and the apoptosis network, it is demonstrated that key participants in these processes are involved in the interactions of those types by which these networks differ from random ones. CONCLUSIONS: FunGeneNet is a web tool aimed at proving the functionality of networks in a wide range of sizes of experimental gene sets, both for different global networks and for different types of interactions. Using examples of thyroid cancer and apoptosis networks, we have shown that the links over-represented in the analyzed network in comparison with the random ones make possible a biological interpretation of the original gene/protein sets. The FunGeneNet web tool for assessment of the functional enrichment of networks is available at http://www-bionet.sscc.ru/fungenenet/ .


Asunto(s)
Redes Reguladoras de Genes , Genómica/métodos , Internet , Apoptosis , Bases de Datos Genéticas , Ontología de Genes , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
10.
BMC Med Genomics ; 11(Suppl 1): 15, 2018 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-29504915

RESUMEN

BACKGROUND: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. RESULTS: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system. CONCLUSIONS: The application of methods of reconstruction and analysis of gene networks is a productive tool for studying the molecular mechanisms of comorbid conditions. The method put forth to rank genes by their importance to the comorbid condition of asthma and hypertension was employed that resulted in prediction of 10 genes, playing the key role in the development of the comorbid condition. The results can be utilised to plan experiments for identification of novel candidate genes along with searching for novel pharmacological targets.


Asunto(s)
Asma/genética , Biomarcadores/análisis , Enfermedades del Sistema Nervioso Central/etiología , Biología Computacional/métodos , Minería de Datos/métodos , Redes Reguladoras de Genes , Hipertensión/genética , Asma/epidemiología , Catalasa/genética , Comorbilidad , Perfilación de la Expresión Génica , Humanos , Hipertensión/epidemiología , Interleucina-10/genética , Programas Informáticos , Receptor Toll-Like 4/genética
11.
J Integr Bioinform ; 15(4)2018 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-30864351

RESUMEN

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.


Asunto(s)
Asma/genética , Biomarcadores/análisis , Biología Computacional/métodos , Redes Reguladoras de Genes , Hipertensión/genética , Asma/epidemiología , Comorbilidad , Minería de Datos , Alemania/epidemiología , Humanos , Hipertensión/epidemiología , Programas Informáticos
12.
Virus Res ; 218: 79-85, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27109913

RESUMEN

Molecular genetic processes generally involve proteins from distinct intracellular localisations. Reactions that follow the same process are distributed among various compartments within the cell. In this regard, the reaction rate and the efficiency of biological processes can depend on the subcellular localisation of proteins. Previously, the authors proposed a method of evaluating the efficiency of biological processes based on the analysis of the distribution of protein subcellular localisation (Popik et al., 2014). Here, NACE is presented, which is an open access web-oriented program that implements this method and allows the user to evaluate the intercompartmental efficiency of human molecular genetic networks. The method has been extended by a new feature that provides the evaluation of the tissue-specific efficiency of networks for more than 2800 anatomical structures. Such assessments are important in cases when molecular genetic pathways in different tissues proceed with the participation of various proteins with a number of intracellular localisations. For example, an analysis of KEGG pathways, conducted using the developed program, showed that the efficiencies of many KEGG pathways are tissue-specific. Analysis of efficiencies of regulatory pathways in the liver, linking proteins of the hepatitis C virus with human proteins involved in the KEGG apoptosis pathway, showed that intercompartmental efficiency might play an important role in host-pathogen interactions. Thus, the developed tool can be useful in the study of the effectiveness of functioning of various molecular genetic networks, including metabolic, regulatory, host-pathogen interactions and others taking into account tissue-specific gene expression. The tool is available via the following link: http://www-bionet.sscc.ru/nace/.


Asunto(s)
Redes Reguladoras de Genes , Hepacivirus/genética , Hepatitis C/genética , FN-kappa B/genética , Programas Informáticos , Proteínas no Estructurales Virales/genética , Apoptosis/genética , Compartimento Celular , Quinasa de Punto de Control 2/genética , Quinasa de Punto de Control 2/metabolismo , Regulación de la Expresión Génica , Hepacivirus/metabolismo , Hepatitis C/metabolismo , Hepatitis C/virología , Hepatocitos/metabolismo , Hepatocitos/virología , Interacciones Huésped-Patógeno , Humanos , Redes y Vías Metabólicas/genética , FN-kappa B/metabolismo , Especificidad de Órganos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Proteínas no Estructurales Virales/metabolismo
13.
Virus Res ; 218: 40-8, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-26673098

RESUMEN

A study of the molecular genetics mechanisms of host-pathogen interactions is of paramount importance in developing drugs against viral diseases. Currently, the literature contains a huge amount of information that describes interactions between HCV and human proteins. In addition, there are many factual databases that contain experimentally verified data on HCV-host interactions. The sources of such data are the original data along with the data manually extracted from the literature. However, the manual analysis of scientific publications is time consuming and, because of this, databases created with such an approach often do not have complete information. One of the most promising methods to provide actualisation and completeness of information is text mining. Here, with the use of a previously developed method by the authors using ANDSystem, an automated extraction of information on the interactions between HCV and human proteins was conducted. As a data source for the text mining approach, PubMed abstracts and full text articles were used. Additionally, external factual databases were analyzed. On the basis of this analysis, a special version of ANDSystem, extended with the HCV interactome, was created. The HCV interactome contains information about the interactions between 969 human and 11 HCV proteins. Among the 969 proteins, 153 'new' proteins were found not previously referred to in any external databases of protein-protein interactions for HCV-host interactions. Thus, the extended ANDSystem possesses a more comprehensive detailing of HCV-host interactions versus other existing databases. It was interesting that HCV proteins more preferably interact with human proteins that were already involved in a large number of protein-protein interactions as well as those associated with many diseases. Among human proteins of the HCV interactome, there were a large number of proteins regulated by microRNAs. It turned out that the results obtained for protein-protein interactions and microRNA-regulation did not depend on how well the proteins were studied, while protein-disease interactions appeared to be dependent on the level of study. In particular, the mean number of diseases linked to well-studied proteins (proteins were considered well-studied if they were mentioned in 50 or more PubMed publications) from the HCV interactome was 20.8, significantly exceeding the mean number of associations with diseases (10.1) for the total set of well-studied human proteins present in ANDSystem. For proteins not highly poorly-studied investigated, proteins from the HCV interactome (each protein was referred to in less than 50 publications) distribution of the number of diseases associated with them had no statistically significant differences from the distribution of the number of diseases associated with poorly-studied proteins based on the total set of human proteins stored in ANDSystem. With this, the average number of associations with diseases for the HCV interactome and the total set of human proteins were 0.3 and 0.2, respectively. Thus, ANDSystem, extended with the HCV interactome, can be helpful in a wide range of issues related to analyzing HCV-host interactions in the search for anti-HCV drug targets. The demo version of the extended ANDSystem covered here containing only interactions between human proteins, genes, metabolites, diseases, miRNAs and molecular-genetic pathways, as well as interactions between human proteins/genes and HCV proteins, is freely available at the following web address: http://www-bionet.sscc.ru/psd/andhcv/.


Asunto(s)
Algoritmos , Minería de Datos/métodos , Hepacivirus/genética , Hepatitis C/genética , Receptores Virales/genética , Proteínas Virales/genética , Minería de Datos/estadística & datos numéricos , Bases de Datos Factuales , Regulación de la Expresión Génica , Hepacivirus/metabolismo , Hepatitis C/metabolismo , Hepatitis C/virología , Interacciones Huésped-Patógeno , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Mapeo de Interacción de Proteínas , PubMed/estadística & datos numéricos , Receptores Virales/metabolismo , Proteínas Virales/metabolismo
14.
BMC Syst Biol ; 9 Suppl 2: S4, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25879409

RESUMEN

BACKGROUND: Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point. RESULTS: The use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia]. CONCLUSIONS: For pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.


Asunto(s)
Redes Reguladoras de Genes , Preeclampsia/genética , Comorbilidad , Minería de Datos , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/patología , Diabetes Gestacional/genética , Diabetes Gestacional/patología , Femenino , Regulación de la Expresión Génica , Estudios de Asociación Genética , Humanos , Obesidad/complicaciones , Obesidad/genética , Obesidad/patología , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Programas Informáticos , Biología de Sistemas
15.
BMC Syst Biol ; 9 Suppl 2: S2, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25881313

RESUMEN

BACKGROUND: Sufficient knowledge of molecular and genetic interactions, which comprise the entire basis of the functioning of living systems, is one of the necessary requirements for successfully answering almost any research question in the field of biology and medicine. To date, more than 24 million scientific papers can be found in PubMed, with many of them containing descriptions of a wide range of biological processes. The analysis of such tremendous amounts of data requires the use of automated text-mining approaches. Although a handful of tools have recently been developed to meet this need, none of them provide error-free extraction of highly detailed information. RESULTS: The ANDSystem package was developed for the reconstruction and analysis of molecular genetic networks based on an automated text-mining technique. It provides a detailed description of the various types of interactions between genes, proteins, microRNA's, metabolites, cellular components, pathways and diseases, taking into account the specificity of cell lines and organisms. Although the accuracy of ANDSystem is comparable to other well known text-mining tools, such as Pathway Studio and STRING, it outperforms them in having the ability to identify an increased number of interaction types. CONCLUSION: The use of ANDSystem, in combination with Pathway Studio and STRING, can improve the quality of the automated reconstruction of molecular and genetic networks. ANDSystem should provide a useful tool for researchers working in a number of different fields, including biology, biotechnology, pharmacology and medicine.


Asunto(s)
Minería de Datos/métodos , Redes Reguladoras de Genes , Programas Informáticos , PubMed , Biología de Sistemas/métodos
16.
BMC Genomics ; 15 Suppl 12: S12, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25563397

RESUMEN

BACKGROUND: Geothermal areas are of great interest for the study of microbial communities. The results of such investigations can be used in a variety of fields (ecology, microbiology, medicine) to answer fundamental questions, as well as those with practical benefits. Uzon caldera is located in the Uzon-Geyser depression that is situated in the centre of the Karym-Semyachin region of the East Kamchatka graben-synclinorium. The microbial communities of Zavarzin spring are well studied; however, its benthic microbial mat has not been previously described. RESULTS: Pyrosequencing of the V3 region of the 16S rRNA gene was used to study the benthic microbial community of the Zavarzin thermal spring (Uzon Caldera, Kamchatka). The community is dominated by bacteria (>95% of all sequences), including thermophilic, chemoorganotrophic Caldiserica (33.0%) and Dictyoglomi (24.8%). The benthic community and the previously examined planktonic community of Zavarzin spring have qualitatively similar, but quantitatively different, compositions. CONCLUSIONS: In this study, we performed a metagenomic analysis of the benthic microbial mat of Zavarzin spring. We compared this benthic community to microbial communities found in the water and of an integral probe consisting of water and bottom sediments. Various phylogenetic groups of microorganisms, including potentially new ones, represent the full-fledged trophic system of Zavarzin. A thorough geochemical study of the spring was performed.


Asunto(s)
Manantiales de Aguas Termales/microbiología , Metagenoma , Archaea/clasificación , Archaea/genética , Archaea/aislamiento & purificación , Archaea/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Elementos Químicos , Sedimentos Geológicos/química , Manantiales de Aguas Termales/análisis , Manantiales de Aguas Termales/química , Minerales/análisis , Federación de Rusia
17.
J Integr Bioinform ; 7(1): 148, 2010 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-21068463

RESUMEN

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).


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Proteínas Portadoras/metabolismo , Biología Computacional/métodos , Cardiomiopatía Dilatada/metabolismo , Gráficos por Computador , Minería de Datos/métodos , Bases de Datos de Proteínas , Femenino , Humanos , Imagenología Tridimensional , Almacenamiento y Recuperación de la Información , Proteínas de la Membrana , PubMed , Programas Informáticos , Biología de Sistemas , Interfaz Usuario-Computador
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