TrackSigFreq: subclonal reconstructions based on mutation signatures and allele frequencies
TrackSigFreq: subclonal reconstructions based on mutation signatures and allele frequencies
复制标题
TrackSigFreq：基于突变特征和等位基因频率的亚克隆重建
DOI：
--
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Alina Selega
中科院分区：
文献类型：
--
作者：
Caitlin F. Harrigan;Yulia Rubanova;Q. Morris;Alina Selega
突变特征是突变类型的模式，其中许多与已知的诱变过程有关。签名活动代表签名生成的突变的比例。在癌症中，细胞可能通过突变积累获得有利的表型，导致肿瘤内该亚群的快速生长。许多亚克隆的存在会使癌症更难治疗，并具有其他临床意义。重建特征活动的变化可以深入了解肿瘤内细胞的进化。最近，我们引入了一种新方法 TrackSig，用于检测单个大块肿瘤样本的特征活动随时间的变化。按照设计，TrackSig 无法识别频率不同但签名活性几乎没有差异的突变群体。在这里，我们提出了这种方法的扩展，TrackSigFreq，它能够根据观察到的突变频率密度和突变特征活动的变化来重建轨迹。 TrackSigFreq 保留了 TrackSig 的优点，即通过分段进行最优且快速的突变聚类，同时对其进行了扩展，使其可以识别具有相似签名活动的不同突变群体。
Mutational signatures are patterns of mutation types, many of which are linked to known mutagenic processes. Signature activity represents the proportion of mutations a signature generates. In cancer, cells may gain advantageous phenotypes through mutation accumulation, causing rapid growth of that subpopulation within the tumour. The presence of many subclones can make cancers harder to treat and have other clinical implications. Reconstructing changes in signature activities can give insight into the evolution of cells within a tumour. Recently, we introduced a new method, TrackSig, to detect changes in signature activities across time from single bulk tumour sample. By design, TrackSig is unable to identify mutation populations with different frequencies but little to no difference in signature activity. Here we present an extension of this method, TrackSigFreq, which enables trajectory reconstruction based on both observed density of mutation frequencies and changes in mutational signature activities. TrackSigFreq preserves the advantages of TrackSig, namely optimal and rapid mutation clustering through segmentation, while extending it so that it can identify distinct mutation populations that share similar signature activities.
影响因子：
9.3
作者：
M. Griffith;Christopher A. Miller;O. Griffith;Kilannin Krysiak;Zachary L. Skidmore;Avinash Ramu;Jason R. Walker;H. Dang;L. Trani;D. Larson;Ryan T. Demeter;M. Wendl;Joshua F. McMichael;Rachel Austin;V. Magrini;S. McGrath;Amy Ly;S. Kulkarni;M. Cordes;C. Fronick;R. Fulton;C. Maher;L. Ding;J. Klco;E. Mardis;T. Ley;R. Wilson
通讯作者：
M. Griffith;Christopher A. Miller;O. Griffith;Kilannin Krysiak;Zachary L. Skidmore;Avinash Ramu;Jason R. Walker;H. Dang;L. Trani;D. Larson;Ryan T. Demeter;M. Wendl;Joshua F. McMichael;Rachel Austin;V. Magrini;S. McGrath;Amy Ly;S. Kulkarni;M. Cordes;C. Fronick;R. Fulton;C. Maher;L. Ding;J. Klco;E. Mardis;T. Ley;R. Wilson