Bulk and single-cell DNA sequencing has enabled reconstructing clonal substructures of somatic tissues from frequency and cooccurrence patterns of somatic variants. However, approaches to characterize phenotypic variations between clones are not established. Here we present cardelino (https://github.com/single-cell-genetics/cardelino), a computational method for inferring the clonal tree configuration and the clone of origin of individual cells assayed using single-cell RNA-seq (scRNA-seq). Cardelino flexibly integrates information from imperfect clonal trees inferred based on bulk exome-seq data, and sparse variant alleles expressed in scRNA-seq data. We apply cardelino to a published cancer dataset and to newly generated matched scRNA-seq and exome-seq data from 32 human dermal fibroblast lines, identifying hundreds of differentially expressed genes between cells from different somatic clones. These genes are frequently enriched for cell cycle and proliferation pathways, indicating a role for cell division genes in somatic evolution in healthy skin.

批量和单细胞DNA测序已能够从体细胞变异的频率和共现模式重建体细胞组织的克隆亚结构。但是，尚未建立表征克隆之间表型变异的方法。在这里，我们介绍cardelino（https://github.com/single-cell-genetics/cardelino），这是一种计算方法，用于推断单细胞RNA-seq（scRNA- seq）。Cardelino可以灵活地整合基于大量外显子组seq数据推断出的不完善克隆树的信息，以及在scRNA-seq数据中表达的稀疏变异等位基因。我们将cardelino应用于已发布的癌症数据集以及来自32个人类皮肤成纤维细胞系的新生成的匹配scRNA-seq和exome-seq数据，从不同的体细胞克隆中鉴定出数百种差异表达的基因。这些基因通常富集细胞周期和增殖途径，表明细胞分裂基因在健康皮肤的体细胞进化中的作用。