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通过半监督学习进行肿瘤类型分类和候选癌症特异性生物标志物发现。

Tumor type classification and candidate cancer-specific biomarkers discovery via semi-supervised learning.

作者信息

Chen Peng, Li Zhenlei, Hong Zhaolin, Zheng Haoran, Zeng Rong

机构信息

School of Computer Science and Technology, University of Science and Technology of China, Hefei 230026, China.

Anhui Key Laboratory of Software Engineering in Computing and Communication, University of Science and Technology of China, Hefei 230026, China.

出版信息

Biophys Rep. 2023 Apr 30;9(2):57-66. doi: 10.52601/bpr.2023.230005.

Abstract

Identifying cancer-related differentially expressed genes provides significant information for diagnosing tumors, predicting prognoses, and effective treatments. Recently, deep learning methods have been used to perform gene differential expression analysis using microarray-based high-throughput gene profiling and have achieved good results. In this study, we proposed a new robust multiple-datasets-based semi-supervised learning model, MSSL, to perform tumor type classification and candidate cancer-specific biomarkers discovery across multiple tumor types and multiple datasets, which addressed the following long-lasting obstacles: (1) the data volume of the existing single dataset is not enough to fully exert the advantages of deep learning; (2) a large number of datasets from different research institutions cannot be effectively used due to inconsistent internal variances and low quality; (3) relatively uncommon cancers have limited effects on deep learning methods. In our article, we applied MSSL to The Cancer Genome Atlas (TCGA) and the Gene Expression Comprehensive Database (GEO) pan-cancer normalized-level3 RNA-seq data and got 97.6% final classification accuracy, which had a significant performance leap compared with previous approaches. Finally, we got the ranking of the importance of the corresponding genes for each cancer type based on classification results and validated that the top genes selected in this way were biologically meaningful for corresponding tumors and some of them had been used as biomarkers, which showed the efficacy of our method.

摘要

识别癌症相关的差异表达基因可为肿瘤诊断、预后预测及有效治疗提供重要信息。近年来,深度学习方法已被用于基于微阵列的高通量基因谱分析来进行基因差异表达分析,并取得了良好效果。在本研究中,我们提出了一种新的基于多数据集的稳健半监督学习模型MSSL,用于跨多种肿瘤类型和多个数据集进行肿瘤类型分类及候选癌症特异性生物标志物发现,该模型解决了以下长期存在的障碍:(1)现有单个数据集的数据量不足以充分发挥深度学习的优势;(2)由于内部方差不一致和质量较低,来自不同研究机构的大量数据集无法得到有效利用;(3)相对罕见的癌症对深度学习方法的影响有限。在我们的文章中,我们将MSSL应用于癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的泛癌标准化三级RNA测序数据,最终分类准确率达到97.6%,与先前方法相比有显著的性能提升。最后,我们根据分类结果得到了每种癌症类型相应基因的重要性排名,并验证了以这种方式选择的顶级基因对相应肿瘤具有生物学意义,其中一些已被用作生物标志物,这表明了我们方法的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d95/10518520/1d4a774d25d3/br-9-2-57-Scheme1.jpg

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