Accurate and sensitive mutational signature analysis with MuSiCal.
Accurate and sensitive mutational signature analysis with MuSiCal.
复制标题
使用 MuSiCal 进行准确、灵敏的突变特征分析。
DOI：
10.1038/s41588-024-01659-0
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发表时间：
2024
期刊：
影响因子：
30.8
通讯作者：
Park,PeterJ
中科院分区：
文献类型：
--
作者：
Jin,Hu;Gulhan,DogaC;Geiger,Benedikt;Ben-Isvy,Daniel;Geng,David;Ljungström,Viktor;Park,PeterJ
突变标记分析是一种用于解释基因组中体细胞突变的最新计算方法。它在癌症数据中的应用增强了我们对驱动肿瘤发生的突变力量的理解，并证明了它为预后和治疗决策提供信息的潜力。然而，发现新的签名和为现有签名分配适当权重的方法学挑战仍然存在，从而阻碍了更广泛的临床应用。在这里，我们提出了突变签名计算器（MuSiCal），一个严格的分析框架与算法，解决标准工作流程中的主要问题。我们的模拟研究表明，MuSiCal优于国家的最先进的算法的签名发现和分配。通过重新分析2,700多个癌症基因组，我们提供了一个改进的签名及其分配目录，发现了当前目录中不存在的9个indel签名，解决了长期存在的模糊“扁平”签名问题，并深入了解了未知病因的签名。我们希望MuSiCal和改进的目录是建立突变签名分析最佳实践的一步。
Mutational signature analysis is a recent computational approach for interpreting somatic mutations in the genome. Its application to cancer data has enhanced our understanding of mutational forces driving tumorigenesis and demonstrated its potential to inform prognosis and treatment decisions. However, methodological challenges remain for discovering new signatures and assigning proper weights to existing signatures, thereby hindering broader clinical applications. Here we present Mutational Signature Calculator (MuSiCal), a rigorous analytical framework with algorithms that solve major problems in the standard workflow. Our simulation studies demonstrate that MuSiCal outperforms state-of-the-art algorithms for both signature discovery and assignment. By reanalyzing more than 2,700 cancer genomes, we provide an improved catalog of signatures and their assignments, discover nine indel signatures absent in the current catalog, resolve long-standing issues with the ambiguous ‘flat’ signatures and give insights into signatures with unknown etiologies. We expect MuSiCal and the improved catalog to be a step towards establishing best practices for mutational signature analysis.