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基于深度对抗学习模型的染色质可及性谱的癌症分类。

Cancer classification based on chromatin accessibility profiles with deep adversarial learning model.

机构信息

Department of Computer Science and Engineering, East China University of Science and Technology, Shanghai, PR China.

Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.

出版信息

PLoS Comput Biol. 2020 Nov 9;16(11):e1008405. doi: 10.1371/journal.pcbi.1008405. eCollection 2020 Nov.

Abstract

Given the complexity and diversity of the cancer genomics profiles, it is challenging to identify distinct clusters from different cancer types. Numerous analyses have been conducted for this propose. Still, the methods they used always do not directly support the high-dimensional omics data across the whole genome (Such as ATAC-seq profiles). In this study, based on the deep adversarial learning, we present an end-to-end approach ClusterATAC to leverage high-dimensional features and explore the classification results. On the ATAC-seq dataset and RNA-seq dataset, ClusterATAC has achieved excellent performance. Since ATAC-seq data plays a crucial role in the study of the effects of non-coding regions on the molecular classification of cancers, we explore the clustering solution obtained by ClusterATAC on the pan-cancer ATAC dataset. In this solution, more than 70% of the clustering are single-tumor-type-dominant, and the vast majority of the remaining clusters are associated with similar tumor types. We explore the representative non-coding loci and their linked genes of each cluster and verify some results by the literature search. These results suggest that a large number of non-coding loci affect the development and progression of cancer through its linked genes, which can potentially advance cancer diagnosis and therapy.

摘要

鉴于癌症基因组图谱的复杂性和多样性,从不同的癌症类型中识别出不同的聚类是具有挑战性的。为此已经进行了许多分析。尽管如此,他们使用的方法并不总是直接支持整个基因组的高维组学数据(例如 ATAC-seq 图谱)。在这项研究中,基于深度对抗学习,我们提出了一种端到端的方法 ClusterATAC,以利用高维特征并探索分类结果。在 ATAC-seq 数据集和 RNA-seq 数据集上,ClusterATAC 都取得了优异的性能。由于 ATAC-seq 数据在研究非编码区域对癌症分子分类的影响方面起着至关重要的作用,我们探索了 ClusterATAC 在泛癌 ATAC 数据集上获得的聚类解决方案。在该解决方案中,超过 70%的聚类是单一肿瘤类型主导的,其余大多数聚类与相似的肿瘤类型相关。我们探索了每个聚类的代表性非编码基因座及其关联基因,并通过文献检索验证了一些结果。这些结果表明,大量的非编码基因座通过其关联基因影响癌症的发生和发展,这可能有助于推进癌症的诊断和治疗。

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