Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom.
The Francis Crick Institute, London, United Kingdom.
PLoS Comput Biol. 2023 Oct 23;19(10):e1011379. doi: 10.1371/journal.pcbi.1011379. eCollection 2023 Oct.
Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient's disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase's ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.
大多数从 DNA 测序中推断体细胞拷贝数改变 (SCNAs) 的计算方法都是单独分析肿瘤样本。然而，对患者疾病的多个肿瘤样本进行测序是一种越来越常见的做法。我们引入了 Refphase，这是一种利用这种多采样方法通过多采样相位推断单倍型特异性拷贝数的算法。我们展示了 Refphase 推断单倍型特异性 SCNAs 并描述其肿瘤内异质性的能力，揭示了在低纯度样本中以前未检测到的等位基因失衡，并在一个包含 99 个肿瘤的 336 个样本的泛癌症队列中发现了全基因组加倍背景下的平行进化。
