Spatial and genomic heterogeneity of tumors is the key for cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their high-resolution localization by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors.

中文翻译：

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Tumoroscope：在肿瘤组织中绘制癌症克隆的概率模型

肿瘤的空间和基因组异质性是癌症进展、治疗和生存的关键。然而，缺乏一种基于点突变直接定位肿瘤组织中的克隆的技术。在这里，我们提出了 Tumoroscope，这是第一个通过整合病理图像、全外显子组测序和空间转录组学数据准确推断癌症克隆及其高分辨率定位的概率模型。与以前的方法相比，Tumoroscope 明确解决了空间转录组学点中克隆比例的去卷积问题。应用于参考前列腺癌数据集和新生成的乳腺癌数据集，Tumoroscope 揭示了肿瘤组织子区域中克隆共定位和互斥的空间模式。我们进一步推断克隆特异性基因表达水平和每个克隆的最高表达基因。总之，Tumoroscope 可以对肿瘤的空间、基因组和表型组织进行综合研究。