Clinical Genomics Analysis Branch, National Cancer Center, Goyang 10408, Republic of Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Nucleic Acids Res. 2018 Jul 2;46(W1):W102-W108. doi: 10.1093/nar/gky406.
Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.
体细胞基因组突变是由于各种内在/外在突变过程和 DNA 修复机制的组合而发生的。不同的分子过程经常在其自身偏好的上下文中产生体细胞突变的不同特征。因此，局部体细胞突变率取决于局部 DNA 序列、基因组中 DNA 复制/RNA 转录动力学和表观基因组染色质组织景观。在这里，我们提出了一个在线计算框架，称为 Mutalisk，它将体细胞突变与各种基因组、转录组和表观基因组特征相关联，以了解导致突变产生的突变过程。这个用户友好的工具探索了局部超突变（kataegis）的存在，将突变谱分解为已知突变特征的最大似然组合，并将突变密度与基因组中的许多调控元件相关联。结果，可以有效地筛选任何查询样本中的体细胞突变的全局模式，从而更深入地了解各种诱变因素。该工具将有助于更有效地对癌症基因组序列进行下游分析，以阐明癌症细胞发生和克隆进化的各种突变过程。Mutalisk 可在 http://mutalisk.org 上免费获得。
