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原发性和转移性肿瘤转录组数据的可视化聚类——相关性和新的陷阱。

Visual Clustering of Transcriptomic Data from Primary and Metastatic Tumors-Dependencies and Novel Pitfalls.

机构信息

Institute of Pathology, Klinikum Stuttgart, 70174 Stuttgart, Germany.

Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany.

出版信息

Genes (Basel). 2022 Jul 26;13(8):1335. doi: 10.3390/genes13081335.

DOI:10.3390/genes13081335
PMID:35893071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9394300/
Abstract

Personalized oncology is a rapidly evolving area and offers cancer patients therapy options that are more specific than ever. However, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP)) on three datasets of metastases ( =682 samples) with three different data transformations (unprocessed, log10 as well as log10 + 1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets ( =616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between the site of resection and cluster formation outcome could be demonstrated, or for datasets consisting of solely metastasis or mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in the interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results highlight the need for a more thorough examination of parameters used in the analysis of clusters.

摘要

个性化肿瘤学是一个快速发展的领域,为癌症患者提供了比以往任何时候都更具针对性的治疗选择。然而,对于转移灶和相应的原发部位的转录组相似性或差异性仍缺乏了解。我们应用两种无监督降维方法(t 分布随机近邻嵌入(t-SNE)和一致流形逼近和投影(UMAP))对三个转移数据集(=682 个样本)进行分析,这三个数据集采用了三种不同的数据转换方式(未处理、以 10 为底的对数以及以 10 为底的对数加 1 的转换值),以可视化潜在的潜在聚类。此外,我们分析了两个包含同一实体的转移灶和原发灶的数据集(=616 个样本),以指出潜在的相似性。使用这些方法,我们不能证明切除部位与聚类形成结果之间存在紧密联系,也不能证明仅包含转移灶或混合数据集的数据集之间存在紧密联系。相反,降维方法和数据转换对可视化聚类结果有显著影响。我们的研究结果强烈表明,在解释可视化聚类方法时,除了初始化和不同的参数外,还应将数据转换视为另一个关键因素。此外,结果突出表明需要更彻底地检查聚类分析中使用的参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/f2d60fc512c3/genes-13-01335-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/a1c81aaf26a7/genes-13-01335-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/78f5cd5ec57d/genes-13-01335-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/0cfdc49e772e/genes-13-01335-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/09afdbbb0201/genes-13-01335-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/e3ab8de1afb2/genes-13-01335-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/f2d60fc512c3/genes-13-01335-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/a1c81aaf26a7/genes-13-01335-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/78f5cd5ec57d/genes-13-01335-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/0cfdc49e772e/genes-13-01335-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/09afdbbb0201/genes-13-01335-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/e3ab8de1afb2/genes-13-01335-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf9/9394300/f2d60fc512c3/genes-13-01335-g006.jpg

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本文引用的文献

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Pre-existing Castration-resistant Prostate Cancer-like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy.原发性前列腺癌中预先存在的去势抵抗性前列腺癌细胞样细胞促进对激素治疗的抵抗。
Eur Urol. 2022 May;81(5):446-455. doi: 10.1016/j.eururo.2021.12.039. Epub 2022 Jan 17.
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DNA methylation profiling as a model for discovery and precision diagnostics in neuro-oncology.DNA 甲基化分析作为神经肿瘤学中发现和精准诊断的模型。
Neuro Oncol. 2021 Nov 2;23(23 Suppl 5):S16-S29. doi: 10.1093/neuonc/noab143.
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Integrated single-cell and bulk RNA sequencing analysis identifies a cancer associated fibroblast-related signature for predicting prognosis and therapeutic responses in colorectal cancer.
整合单细胞和批量RNA测序分析确定了一种与癌症相关的成纤维细胞相关特征,用于预测结直肠癌的预后和治疗反应。
Cancer Cell Int. 2021 Oct 20;21(1):552. doi: 10.1186/s12935-021-02252-9.
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Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis.单细胞RNA测序揭示乳腺癌淋巴结转移的细胞异质性和转录组图谱。
Oncogenesis. 2021 Oct 5;10(10):66. doi: 10.1038/s41389-021-00355-6.
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Identifying New Potential Biomarkers in Adrenocortical Tumors Based on mRNA Expression Data Using Machine Learning.基于机器学习的mRNA表达数据识别肾上腺皮质肿瘤中的新潜在生物标志物
Cancers (Basel). 2021 Sep 17;13(18):4671. doi: 10.3390/cancers13184671.
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Cell Rep. 2021 Jul 27;36(4):109442. doi: 10.1016/j.celrep.2021.109442.
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DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma.基于 DNA 甲基化的预测转移性黑色素瘤对免疫检查点抑制的反应。
J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2020-002226.
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