Cancer Research Program, Houston Methodist Research Institute, Houston, Texas, USA.
Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Nucleic Acids Res. 2018 Jan 4;46(D1):D1011-D1017. doi: 10.1093/nar/gkx956.
Large-scale oncogenomic studies have identified few frequently mutated cancer drivers and hundreds of infrequently mutated drivers. Defining the biological context for rare driving events is fundamentally important to increasing our understanding of the druggable pathways in cancer. Sleeping Beauty (SB) insertional mutagenesis is a powerful gene discovery tool used to model human cancers in mice. Our lab and others have published a number of studies that identify cancer drivers from these models using various statistical and computational approaches. Here, we have integrated SB data from primary tumor models into an analysis and reporting framework, the Sleeping Beauty Cancer Driver DataBase (SBCDDB, http://sbcddb.moffitt.org), which identifies drivers in individual tumors or tumor populations. Unique to this effort, the SBCDDB utilizes a single, scalable, statistical analysis method that enables data to be grouped by different biological properties. This allows for SB drivers to be evaluated (and re-evaluated) under different contexts. The SBCDDB provides visual representations highlighting the spatial attributes of transposon mutagenesis and couples this functionality with analysis of gene sets, enabling users to interrogate relationships between drivers. The SBCDDB is a powerful resource for comparative oncogenomic analyses with human cancer genomics datasets for driver prioritization.
大规模的肿瘤基因组学研究已经确定了少数经常发生突变的癌症驱动基因和数百个罕见突变的驱动基因。定义罕见驱动事件的生物学背景对于增加我们对癌症可药物途径的理解至关重要。睡眠美人(SB)插入诱变是一种强大的基因发现工具,用于在小鼠中模拟人类癌症。我们实验室和其他实验室已经发表了许多研究报告,使用各种统计和计算方法从这些模型中鉴定出癌症驱动基因。在这里,我们将来自原发性肿瘤模型的 SB 数据整合到一个分析和报告框架中,即睡眠美人癌症驱动子数据库(SBCDDB,http://sbcddb.moffitt.org),该数据库可识别单个肿瘤或肿瘤群体中的驱动子。这项工作的独特之处在于,SBCDDB 利用了一种单一的、可扩展的统计分析方法,允许根据不同的生物学特性对数据进行分组。这使得 SB 驱动子可以在不同的环境下进行评估(和重新评估)。SBCDDB 提供了突出转座子诱变空间属性的可视化表示,并将此功能与基因集分析相结合,使用户能够探究驱动子之间的关系。SBCDDB 是一个强大的资源,可用于与人类癌症基因组数据集进行比较肿瘤基因组学分析,以确定驱动子的优先级。