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基于网络分析和机器学习的肝细胞癌关键基因筛选。

Screening of Hub Genes in Hepatocellular Carcinoma Based on Network Analysis and Machine Learning.

机构信息

School of Bioinformatics, Chongqing University of Posts and Telecommunications, 400000, China.

出版信息

Comput Math Methods Med. 2022 Nov 28;2022:7300788. doi: 10.1155/2022/7300788. eCollection 2022.

DOI:10.1155/2022/7300788
PMID:36479313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9722289/
Abstract

Hepatocellular carcinoma (LIHC) is the fifth common cancer worldwide, and it requires effective diagnosis and treatment to prevent aggressive metastasis. The purpose of this study was to construct a machine learning-based diagnostic model for the diagnosis of liver cancer. Using weighted correlation network analysis (WGCNA), univariate analysis, and Lasso-Cox regression analysis, protein-protein interactions network analysis is used to construct gene networks from transcriptome data of hepatocellular carcinoma patients and find hub genes for machine learning. The five models, including gradient boosting, random forest, support vector machine, logistic regression, and integrated learning, were to identify a multigene prediction model of patients. Immunological assessment, TP53 gene mutation and promoter methylation level analysis, and KEGG pathway analysis were performed on these groups. Potential drug molecular targets for the corresponding hepatocellular carcinomas were obtained by molecular docking for analysis, resulting in the screening of 2 modules that may be relevant to the survival of hepatocellular carcinoma patients, and the construction of 5 diagnostic models and multiple interaction networks. The modes of action of drug-molecule interactions that may be effective against hepatocellular carcinoma core genes CCNA2, CCNB1, and CDK1 were investigated. This study is expected to provide research ideas for early diagnosis of hepatocellular carcinoma.

摘要

肝细胞癌(LIHC)是全球第五大常见癌症,需要有效的诊断和治疗方法来预防侵袭性转移。本研究旨在构建基于机器学习的肝癌诊断模型。使用加权相关网络分析(WGCNA)、单变量分析和 Lasso-Cox 回归分析,对肝细胞癌患者的转录组数据进行蛋白质-蛋白质相互作用网络分析,构建基因网络,并找到用于机器学习的枢纽基因。使用梯度提升、随机森林、支持向量机、逻辑回归和集成学习等 5 种模型,从这些组中识别出患者的多基因预测模型。对这些组进行免疫评估、TP53 基因突变和启动子甲基化水平分析以及 KEGG 通路分析。通过分子对接进行分析,获得了对应肝细胞癌的潜在药物分子靶标,筛选出 2 个可能与肝细胞癌患者生存相关的模块,并构建了 5 个诊断模型和多个交互网络。研究了可能对肝细胞癌核心基因 CCNA2、CCNB1 和 CDK1 有效的药物分子相互作用的作用方式。本研究有望为肝细胞癌的早期诊断提供研究思路。

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