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Identification of candidate disease genes in patients with common variable immunodeficiency

摘要Background:Common variable immunodeficiency (CVID),the most prevalent form of primary immunodeficiency (PID),is characterized by hypogammaglobulinemia and recurrent infections.Understanding protein-protein interaction (PPI) networks of CVID genes and identifying candidate CVID genes are critical steps in facilitating the early diagnosis of CVID.Here,the aim was to investigate PPI networks of CVID genes and identify candidate CVID genes using computation techniques.Methods:Network density and biological distance were used to study PPI data for CVID and PID genes obtained from the STRING database.Gene expression data of patients with CVID were obtained from the Gene Expression Omnibus,and then Pearson's correlation coefficient,a PPI database,and Kyoto Encyclopedia of Genes and Genomes were used to identify candidate CVID genes.We then evaluated our predictions and identified differentially expressed CVID genes.Results:The majority of CVID genes are characterized by a high network density and small biological distance,whereas most PID genes are characterized by a low network density and large biological distance,indicating that CVID genes are more functionally similar to each other and closely interact with one other compared with PID genes.Subsequently,we identified 172 CVID candidate genes that have similar biological functions to known CVID genes,and eight genes were recently reported as CVID-related genes.MYC,a candidate gene,was down-regulated in CVID duodenal biopsies,but up-regulated in blood samples compared with levels in healthy controls.Conclusion:Our findings will aid in a better understanding of the complex of CVID genes,possibly further facilitating the early diagnosis of CVID.

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作者单位 Department of Medical Biochemistry and Biophysics, Institute of Natural Sciences and Mathematics, Ural Federal University,Ekaterinburg 620000, Russia [1] Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620000, Russia;Department of immunochemistry, Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620000, Russia [2] Department of Medical Biochemistry and Biophysics, Institute of Natural Sciences and Mathematics, Ural Federal University,Ekaterinburg 620000, Russia;Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620000, Russia [3]
栏目名称 RESEARCH ARTICLES
发布时间 2019-12-30
基金项目
This study was funded by the Act 211 Government of the Russian Federation the IIP UB RAS project
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