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通过微阵列分析筛选潜在基因,这些基因有助于白念珠菌对大环内酯类药物的耐药性。

Screening of potential genes contributing to the macrocycle drug resistance of C. albicans via microarray analysis.

机构信息

Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Department of Nephrology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046011, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):7527-7533. doi: 10.3892/mmr.2017.7562. Epub 2017 Sep 20.

Abstract

The aim of the present study was to investigate the potential genes involved in drug resistance of Candida albicans (C. albicans) by performing microarray analysis. The gene expression profile of GSE65396 was downloaded from the Gene Expression Omnibus, including a control, 15‑min and 45‑min macrocyclic compound RF59‑treated group with three repeats for each. Following preprocessing using RAM, the differentially expressed genes (DEGs) were screened using the Limma package. Subsequently, the Kyoto Encyclopedia of Genes and Genomes pathways of these genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery. Based on interactions estimated by the Search Tool for Retrieval of Interacting Gene, the protein‑protein interaction (PPI) network was visualized using Cytoscape. Subnetwork analysis was performed using ReactomeFI. A total of 154 upregulated and 27 downregulated DEGs were identified in the 15‑min treated group, compared with the control, and 235 upregulated and 233 downregulated DEGs were identified in the 45‑min treated group, compared with the control. The upregulated DEGs were significantly enriched in the ribosome pathway. Based on the PPI network, PRP5, RCL1, NOP13, NOP4 and MRT4 were the top five nodes in the 15‑min treated comparison. GIS2, URA3, NOP58, ELP3 and PLP7 were the top five nodes in the 45‑min treated comparison, and its subnetwork was significantly enriched in the ribosome pathway. The macrocyclic compound RF59 had a notable effect on the ribosome and its associated pathways of C. albicans. RCL1, NOP4, MRT4, GIS2 and NOP58 may be important in RF59‑resistance.

摘要

本研究旨在通过微阵列分析探讨白色念珠菌(Candida albicans,C. albicans)耐药相关的潜在基因。从基因表达综合数据库(Gene Expression Omnibus,GEO)中下载 GSE65396 数据集,包括对照组、15 分钟和 45 分钟大环化合物 RF59 处理组,每组重复 3 次。使用 RAM 进行预处理后,采用 Limma 包筛选差异表达基因(differentially expressed genes,DEGs)。随后,采用数据库注释、可视化和综合发现(Database for Annotation, Visualization and Integrated Discovery,DAVID)分析这些基因的京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路。根据搜索基因交互作用工具(Search Tool for Retrieval of Interacting Gene,STRING)估计的相互作用,使用 Cytoscape 可视化蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。采用 ReactomeFI 进行子网络分析。与对照组相比,15 分钟处理组中鉴定出 154 个上调和 27 个下调的 DEGs,45 分钟处理组中鉴定出 235 个上调和 233 个下调的 DEGs。上调的 DEGs 显著富集于核糖体通路。根据 PPI 网络,在 15 分钟处理比较中,PRP5、RCL1、NOP13、NOP4 和 MRT4 是前五个节点。在 45 分钟处理比较中,GIS2、URA3、NOP58、ELP3 和 PLP7 是前五个节点,其子网络显著富集于核糖体通路。大环化合物 RF59 对白色念珠菌核糖体及其相关通路有显著影响。RCL1、NOP4、MRT4、GIS2 和 NOP58 可能在 RF59 耐药中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7881/5865886/c345774ebeba/mmr-16-05-7527-g00.jpg

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