Data from: Sweepstake evolution revealed by population-genetic analysis of copy-number alterations in single genomes of breast cancer

Single-cell sequencing is a promising technology that can address cancer cell evolution by identifying genetic alterations in individual cells. In a recent study, genome-wide DNA copy numbers of single cells were accurately quantified by single-cell sequencing in breast cancers. Phylogenetic tree analysis revealed genetically distinct populations, each consisting of homogeneous cells. Bioinformatics methods based on population genetics should be further developed to quantitatively analyse the single-cell sequencing data. We developed a bioinformatics framework that was combined with molecular-evolution theories to analyse copy-number losses. This analysis revealed that most deletions in the breast cancers at the single-cell level were generated by simple stochastic processes. A non-standard type of coalescent theory – the multiple-merger coalescent model – aided by approximate Bayesian computation fit well with the data, allowing us to estimate the population-genetic parameters in addition to false-positive and false-negative rates. The estimated parameters suggest that the cancer cells underwent sweepstake evolution, where only 1 or very few parental cells produced a descendant cell population. We conclude that breast cancer cells successively substitute in a tumour mass, and the high reproduction of only a portion of cancer cells may confer high adaptability to this cancer.单细胞测序（Single-cell sequencing）是一项极具前景的技术，可通过识别单个细胞内的遗传变异解析癌细胞进化过程。近期一项研究借助单细胞测序，精准定量了乳腺癌单细胞的全基因组DNA拷贝数。系统发育树分析（Phylogenetic tree analysis）揭示了多个遗传异质性群体，每个群体均由同质细胞构成。当前应进一步发展基于群体遗传学（population genetics）的生物信息学方法，以对单细胞测序数据开展定量分析。本研究开发了一套结合分子进化理论（molecular-evolution theories）的生物信息学框架，用于分析拷贝数丢失（copy-number losses）事件。该分析发现，乳腺癌单细胞层面的多数缺失由简单随机过程产生。一类非标准溯祖理论（coalescent theory）——多分支溯祖模型（multiple-merger coalescent model）结合近似贝叶斯计算（approximate Bayesian computation）可很好地适配实验数据，借此我们不仅能估算群体遗传学参数（population-genetic parameters），还可获得假阳性率与假阴性率。估算参数结果显示，癌细胞经历了抽奖式进化（sweepstake evolution）：仅1个或极少量亲本细胞可产生子代细胞群体。综上，乳腺癌细胞在肿瘤团块（tumour mass）中依次完成替代，仅部分癌细胞具备高繁殖能力，这或许赋予了该癌症极强的适应性。