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的遗传变异（genetic alterations），解析癌细胞的演化过程。在近期一项研究中，科研人员通过单细胞测序技术对乳腺癌患者单细胞的全基因组DNA拷贝数进行了精准定量。系统发育树（phylogenetic tree）分析揭示了多个遗传特征迥异的细胞群，每个细胞群均由基因均一的癌细胞构成。基于群体遗传学的生物信息学方法仍有待进一步开发，以实现对单细胞测序数据的定量分析。本研究团队开发了一套结合分子演化理论的生物信息学框架，用于分析拷贝数缺失（copy-number losses）事件。该分析结果表明，乳腺癌单细胞层面的绝大多数基因缺失均由简单的随机过程所产生。我们采用非标准溯祖理论（coalescent theory）——多分支溯合模型（multiple-merger coalescent model）——结合近似贝叶斯计算（approximate Bayesian computation）对数据进行拟合，借此不仅可以估算群体遗传学参数，还能得到假阳性（false-positive）与假阴性（false-negative）率的估计值。估算得到的参数显示，癌细胞经历了抽奖式演化（sweepstake evolution）：仅由1个或极少数亲本细胞即可产生子代细胞群。本研究得出结论：乳腺癌细胞在肿瘤组织中依次完成替代演化，仅少数癌细胞具备高增殖能力，这或许赋予了该癌症极强的适应性。