背景:正在开发大量算法来从基因组测序数据重建个体肿瘤的进化模型。大多数方法可以分析通过批量多区域测序实验或单个癌细胞的测序收集的多个样品。然而,很少相同的方法可以支持这两种数据类型。
结果:我们介绍TRaIT,一个推断突变图的计算框架,该模型对驱动肿瘤进化的多种类型体细胞改变的积累进行建模。与其他工具相比,TRaIT支持同一统计框架内的多区域和单细胞测序数据,并提供表达模型,捕捉许多复杂的进化现象。TRAIT提高了准确性,与竞争方法相比,对数据特定错误和计算复杂性的鲁棒性。
结论:我们表明,将TRaIT应用于单细胞和多区域癌症数据集可以产生准确可靠的单肿瘤进化模型,量化肿瘤内异质性的程度,并产生新的可测试的实验假设。
BACKGROUND: A large number of algorithms is being developed to reconstruct evolutionary models of individual tumours from genome sequencing data. Most methods can analyze multiple samples collected either through bulk multi-region sequencing experiments or the sequencing of individual cancer cells. However, rarely the same method can support both data types.
RESULTS: We introduce TRaIT, a computational framework to infer mutational graphs that model the accumulation of multiple types of somatic alterations driving tumour evolution. Compared to other tools, TRaIT supports multi-region and single-cell sequencing data within the same statistical framework, and delivers expressive models that capture many complex evolutionary phenomena. TRaIT improves accuracy, robustness to data-specific errors and computational complexity compared to competing methods.
CONCLUSIONS: We show that the application of TRaIT to single-cell and multi-region cancer datasets can produce accurate and reliable models of single-tumour evolution, quantify the extent of intra-tumour heterogeneity and generate new testable experimental hypotheses.