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面向鉴定导致患者多组学特征相似的基因:以急性髓系白血病为例的研究。

Towards Identification of Genes Contributing to Similarity of Patients' Multi-Omics Profiles: A Case Study of Acute Myeloid Leukemia.

机构信息

School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.

出版信息

Genes (Basel). 2023 Sep 13;14(9):1795. doi: 10.3390/genes14091795.

Abstract

We propose a computational framework for selecting biologically plausible genes identified by clustering of multi-omics data that reveal patients' similarity, thus giving researchers a more comprehensive view on any given disease. We employ spectral clustering of a similarity network created by fusion of three similarity networks, based on mRNA expression of immune genes, miRNA expression and DNA methylation data, using SNF_v2.1 software. For each cluster, we rank multi-omics features, ensuring the best separation between clusters, and select the top-ranked features that preserve clustering. To find genes targeted by DNA methylation and miRNAs found in the top-ranked features, we use chromosome-conformation capture data and miRNet2.0 software, respectively. To identify informative genes, these combined sets of target genes are analyzed in terms of their enrichment in somatic/germline mutations, GO biological processes/pathways terms and known sets of genes considered to be important in relation to a given disease, as recorded in the Molecular Signature Database from GSEA. The protein-protein interaction (PPI) networks were analyzed to identify genes that are hubs of PPI networks. We used data recorded in The Cancer Genome Atlas for patients with acute myeloid leukemia to demonstrate our approach, and discuss our findings in the context of results in the literature.

摘要

我们提出了一个计算框架,用于选择通过聚类多组学数据识别出的具有生物学意义的基因,这些数据揭示了患者之间的相似性,从而为研究人员提供了更全面的疾病视角。我们使用 SNF_v2.1 软件,基于免疫基因的 mRNA 表达、miRNA 表达和 DNA 甲基化数据,融合三种相似性网络构建相似性网络,对其进行谱聚类。对于每个聚类,我们对多组学特征进行排名,确保聚类之间的最佳分离,并选择能够保留聚类的最佳排名特征。为了找到在排名靠前的特征中发现的 DNA 甲基化和 miRNA 靶向的基因,我们分别使用染色体构象捕获数据和 miRNet2.0 软件。为了识别信息基因,我们从体细胞/种系突变、GO 生物过程/途径术语以及记录在 GSEA 的分子特征数据库中与特定疾病相关的重要基因集合的角度,分析这些目标基因的组合集。分析蛋白质-蛋白质相互作用 (PPI) 网络,以识别 PPI 网络中的枢纽基因。我们使用记录在 The Cancer Genome Atlas 中的急性髓性白血病患者的数据来演示我们的方法,并在文献结果的背景下讨论我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ff9/10531350/352b50e0c1ea/genes-14-01795-g001.jpg

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