Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Nat Biotechnol. 2014 Nov;32(11):1106-12. doi: 10.1038/nbt.3027. Epub 2014 Oct 26.
The development of high-throughput sequencing technologies has advanced our understanding of cancer. However, characterizing somatic structural variants in tumor genomes is still challenging because current strategies depend on the initial alignment of reads to a reference genome. Here, we describe SMUFIN (somatic mutation finder), a single program that directly compares sequence reads from normal and tumor genomes to accurately identify and characterize a range of somatic sequence variation, from single-nucleotide variants (SNV) to large structural variants at base pair resolution. Performance tests on modeled tumor genomes showed average sensitivity of 92% and 74% for SNVs and structural variants, with specificities of 95% and 91%, respectively. Analyses of aggressive forms of solid and hematological tumors revealed that SMUFIN identifies breakpoints associated with chromothripsis and chromoplexy with high specificity. SMUFIN provides an integrated solution for the accurate, fast and comprehensive characterization of somatic sequence variation in cancer.
高通量测序技术的发展增进了我们对癌症的理解。然而，由于当前的策略依赖于将读取初始比对到参考基因组，因此对肿瘤基因组中的体细胞结构变体进行特征描述仍然具有挑战性。在这里，我们描述了 SMUFIN（体细胞突变发现者），这是一个单一的程序，可以直接比较正常和肿瘤基因组的序列读取，以准确识别和描述一系列体细胞序列变异，从单核苷酸变异（SNV）到碱基对分辨率的大型结构变体。对模型化肿瘤基因组的性能测试表明，SNV 和结构变体的平均灵敏度分别为 92%和 74%，特异性分别为 95%和 91%。对实体瘤和血液系统肿瘤的侵袭性形式的分析表明，SMUFIN 能够以高特异性识别与染色质碎裂和染色质复合相关的断点。SMUFIN 为癌症中体细胞序列变异的准确、快速和全面特征描述提供了一个集成的解决方案。
