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使用独立成分分析对食管癌转录组进行Meta分析。

Meta-Analysis of Esophageal Cancer Transcriptomes Using Independent Component Analysis.

作者信息

Ashenova Ainur, Daniyarov Asset, Molkenov Askhat, Sharip Aigul, Zinovyev Andrei, Kairov Ulykbek

机构信息

Laboratory of Bioinformatics and Systems Biology, National Laboratory Astana, Center for Life Sciences, Nazarbayev University, Nur-Sultan, Kazakhstan.

Department of Biology, School of Sciences and Humanities, Nazarbayev University, Nur-Sultan, Kazakhstan.

出版信息

Front Genet. 2021 Oct 21;12:683632. doi: 10.3389/fgene.2021.683632. eCollection 2021.

Abstract

Independent Component Analysis is a matrix factorization method for data dimension reduction. ICA has been widely applied for the analysis of transcriptomic data for blind separation of biological, environmental, and technical factors affecting gene expression. The study aimed to analyze the publicly available esophageal cancer data using the ICA for identification and comprehensive analysis of reproducible signaling pathways and molecular signatures involved in this cancer type. In this study, four independent esophageal cancer transcriptomic datasets from GEO databases were used. A bioinformatics tool « BiODICA-Independent Component Analysis of Big Omics Data» was applied to compute independent components (ICs). Gene Set Enrichment Analysis (GSEA) and ToppGene uncovered the most significantly enriched pathways. Construction and visualization of gene networks and graphs were performed using the Cytoscape, and HPRD database. The correlation graph between decompositions into 30 ICs was built with absolute correlation values exceeding 0.3. Clusters of components-pseudocliques were observed in the structure of the correlation graph. The top 1,000 most contributing genes of each ICs in the pseudocliques were mapped to the PPI network to construct associated signaling pathways. Some cliques were composed of densely interconnected nodes and included components common to most cancer types (such as cell cycle and extracellular matrix signals), while others were specific to EC. The results of this investigation may reveal potential biomarkers of esophageal carcinogenesis, functional subsystems dysregulated in the tumor cells, and be helpful in predicting the early development of a tumor.

摘要

独立成分分析是一种用于数据降维的矩阵分解方法。独立成分分析已被广泛应用于转录组数据的分析,以盲目分离影响基因表达的生物学、环境和技术因素。该研究旨在使用独立成分分析来分析公开可用的食管癌数据,以识别和全面分析与这种癌症类型相关的可重复信号通路和分子特征。在本研究中,使用了来自基因表达综合数据库(GEO)的四个独立的食管癌转录组数据集。应用一种生物信息学工具“BiODICA - 大数据组学数据的独立成分分析”来计算独立成分(ICs)。基因集富集分析(GSEA)和ToppGene揭示了最显著富集的通路。使用Cytoscape和HPRD数据库进行基因网络和图谱的构建与可视化。构建了分解为30个独立成分的相关图,其绝对相关值超过0.3。在相关图的结构中观察到成分伪团簇。将伪团簇中每个独立成分的前1000个最具贡献的基因映射到蛋白质 - 蛋白质相互作用(PPI)网络,以构建相关的信号通路。一些团簇由紧密相连的节点组成,包括大多数癌症类型共有的成分(如细胞周期和细胞外基质信号),而其他团簇则是食管癌特有的。这项研究的结果可能揭示食管癌发生的潜在生物标志物、肿瘤细胞中失调的功能子系统,并有助于预测肿瘤的早期发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e96f/8594933/a08c88a6e2ee/fgene-12-683632-g001.jpg

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