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ClonArch: Visualizing the Spatial Clonal Architecture of Tumors

By Jiaqi Wu, Mohammed El-Kebir

Posted 07 Apr 2020
bioRxiv DOI: 10.1101/2020.04.06.027912 (published DOI: 10.1093/bioinformatics/btaa471)

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 intra-tumor heterogeneity.

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