Tumor cell population consists of genetically heterogeneous subpopulations, known as subclones. Bulk sequencing data using high-throughput sequencing technology provide total and variant DNA and RNA read counts for many nucleotide loci as a mixture of signals from different subclones. We present RNDClone as a tool to deconvolute the mixture and reconstruct the subclones with distinct DNA genotypes and RNA expression profiles. In particular, we infer the number and population frequencies of subclones as well as subclonal copy numbers, variant allele numbers and gene expression levels by jointly modeling DNA and RNA read counts from the same tumor samples based on generalized latent factor models. Incorporating data at the RNA level provides new insights into intra-tumor heterogeneity in addition to the existing DNA-based inference. Performance of RNDClone is assessed using simulated and real-world datasets, including an analysis of three samples from a lung cancer patient in The Cancer Genome Atlas (TCGA). A potential fatal subclone is identified from the primary tumor which could explain the rapid prognosis and sudden death of the patient despite a promising diagnosis by conventional standards. The R package $\mathtt{RNDClone}$ is available in the Supplementary Material (Zhou et al. (2020)) and online at https://github.com/tianjianzhou/RNDClone.

中文翻译：

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RNDClone：基于DNA和RNA序列数据整合的肿瘤亚克隆重建

肿瘤细胞群由遗传上异质的亚群组成，称为亚克隆。使用高通量测序技术的批量测序数据提供了许多核苷酸位点的总DNA和变异DNA和RNA读数计数，这些读数来自不同亚克隆的信号混合物。我们目前RNDClone作为解卷积混合物和重建具有独特的DNA基因型和RNA表达谱的亚克隆的工具。尤其是，我们通过基于广义潜在因子模型共同模拟来自同一肿瘤样本的DNA和RNA读数计数，推断亚克隆的数量和种群频率以及亚克隆拷贝数，变异等位基因数量和基因表达水平。除了基于DNA的现有推断外，在RNA级别整合数据还提供了有关肿瘤内异质性的新见解。RNDClone的性能使用模拟和真实数据集进行评估，包括对《癌症基因组图谱》（TCGA）中来自肺癌患者的三个样本的分析。从原发性肿瘤中鉴定出了潜在的致命亚克隆，尽管常规标准已作出了有希望的诊断，但仍可解释患者的快速预后和猝死。R包$ \ mathtt {RNDClone} $可在补充材料（Zhou等人（2020年））中找到，也可以在线访问https://github.com/tianjianzhou/RNDClone。从原发性肿瘤中鉴定出了潜在的致命亚克隆，尽管常规标准已作出了有希望的诊断，但仍可解释患者的快速预后和猝死。R包$ \ mathtt {RNDClone} $可在补充材料（Zhou等人（2020年））中找到，也可以在线访问https://github.com/tianjianzhou/RNDClone。从原发性肿瘤中鉴定出了潜在的致命亚克隆，尽管常规标准已作出了有希望的诊断，但仍可解释患者的快速预后和猝死。R包$ \ mathtt {RNDClone} $可在补充材料（Zhou等人（2020年））中找到，也可以在线访问https://github.com/tianjianzhou/RNDClone。