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- 저자 : András Gézsi (검색결과 3 건)
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Systems biology approaches to investigating the roles of extracellular vesicles in human diseases
András Gézsi,Árpád Kovács,Tamás Visnovitz,Edit I. Buzás 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
substantial attention as carriers of complex intercellular information. They have been implicated in a wide variety of biological processes in health and disease. They are also considered to hold promise for future diagnostics and therapy. EVs are characterized by a previously underappreciated heterogeneity. The heterogeneity and molecular complexity of EVs necessitates high-throughput analytical platforms for detailed analysis. Recently, mass spectrometry, nextgeneration sequencing and bioinformatics tools have enabled detailed proteomic, transcriptomic, glycomic, lipidomic, metabolomic, and genomic analyses of EVs. Here, we provide an overview of systems biology experiments performed in the field of EVs. Furthermore, we provide examples of how in silico systems biology approaches can be used to identify correlations between genes involved in EV biogenesis and human diseases. Using a knowledge fusion system, we investigated whether certain groups of proteins implicated in the biogenesis/release of EVs were associated with diseases and phenotypes. Furthermore, we investigated whether these proteins were enriched in publicly available transcriptomic datasets using gene set enrichment analysis methods. We found associations between key EV biogenesis proteins and numerous diseases, which further emphasizes the key role of EVs in human health and disease.
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Gergely Temesi,Viktor Virág,Éva Hadadi,Ildikó Ungvári,Lili E Fodor,András Bikov,Adrienne Nagy,Gabriella Gálffy,Lilla Tamási,Ildikó Horváth,András Kiss,Gábor Hullám,András Gézsi,Péter Sárközy,Péter Ant 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.6
Purpose:Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma. Methods: In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing. Results: The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7×10-5) in SCIN and 0.56 (0.42-0.76; P=1.2×10-4) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics. Conclusions: Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies.
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Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy
Lili E Fodor,András Gézsi,Ildikó Ungvári,Ágnes F. Semsei,Zsófia Gál,Adrienne Nagy,Gabriella Gálffy,Lilla Tamási,András Kiss,Péter Antal,Csaba Szalai 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.3
Purpose: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. Methods: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA). Results: The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other. Conclusions: Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.
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