ClonArch: visualizing the spatial clonal architecture of tumors
ClonArch: visualizing the spatial clonal architecture of tumors
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DOI：
10.1093/bioinformatics/btaa471
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发表时间：
2020-04
期刊：
影响因子：
5.8
通讯作者：
Jiaqi Wu;M. El-Kebir
中科院分区：
文献类型：
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作者：
Jiaqi Wu;M. El-Kebir
动机癌症是由体细胞突变的积累引起的，这些突变导致形成不同的细胞群（称为克隆）。由此产生的克隆结构是复发和治疗耐药的主要原因。随着 DNA 测序技术成本的降低，包含许多空间测序样本的丰富的癌症基因组数据集变得越来越可用，从而能够推断出不同空间坐标的高分辨率肿瘤克隆和患病率。虽然肿瘤进化的时间和系统发育方面，例如随时间的克隆进化和克隆对治疗的反应，通常在各种克隆进化图中可视化，但缺少揭示空间克隆结构的视觉分析方法。结果 本文介绍了 ClonArch，这是一种基于网络的工具，可以交互式地可视化单个肿瘤块中克隆的系统发育树和空间分布。 ClonArch 使用行进方块算法绘制闭合边界，表示真实或模拟肿瘤中克隆的存在。 ClonArch 使研究人员能够检查不同流行阈值和跨多个系统发育树的相关突变子集的空间克隆结构。除了具有不同数量活检的模拟肿瘤之外，我们还展示了 ClonArch 在具有约 280 个测序活检的肝细胞癌肿瘤上的使用。 ClonArch 提供了一种交互式检查肿瘤空间克隆结构的自动化方法，有助于对肿瘤内异质性的空间方面进行临床和生物学解释。可用性 https://github.com/elkebir-group/ClonArch
Motivation Cancer is caused by the accumulation of somatic mutations that lead to the formation of distinct populations of cells, called clones. The resulting clonal architecture is the main cause of relapse and resistance to treatment. With decreasing costs in DNA sequencing technology, rich cancer genomics datasets with many spatial sequencing samples are becoming increasingly available, enabling the inference of high-resolution tumor clones and prevalences across different spatial coordinates. While temporal and phylogenetic aspects of tumor evolution, such as clonal evolution over time and clonal response to treatment, are commonly visualized in various clonal evolution diagrams, visual analytics methods that reveal the spatial clonal architecture are missing. Results This paper introduces ClonArch, a web-based tool to interactively visualize the phylogenetic tree and spatial distribution of clones in a single tumor mass. ClonArch uses the marching squares algorithm to draw closed boundaries representing the presence of clones in a real or simulated tumor. ClonArch enables researchers to examine the spatial clonal architecture of a subset of relevant mutations at different prevalence thresholds and across multiple phylogenetic trees. In addition to simulated tumors with varying number of biopsies, we demonstrate the use of ClonArch on a hepatocellular carcinoma tumor with ~280 sequencing biopsies. ClonArch provides an automated way to interactively examine the spatial clonal architecture of a tumor, facilitating clinical and biological interpretations of the spatial aspects of intratumor heterogeneity. Availability https://github.com/elkebir-group/ClonArch