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SBCDDB: Sleeping Beauty Cancer Driver Database for gene discovery in mouse models of human cancers

机译:SBCDDB:睡美人癌症驱动程序数据库用于在人类癌症的小鼠模型中发现基因

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摘要

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, ), 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.
机译:大规模的肿瘤基因组学研究已经确定了很少有频繁突变的癌症驱动因子和数百个很少突变的驱动因子。定义罕见驾驶事件的生物学背景对于增进我们对癌症中可药物途径的理解至关重要。睡美人(SB)插入诱变是一种功能强大的基因发现工具,用于在小鼠中模拟人类癌症。我们的实验室和其他机构发表了许多研究,使用各种统计和计算方法从这些模型中识别出癌症驱动因素。在这里,我们将来自原发肿瘤模型的SB数据整合到了一个分析和报告框架中,即Sleeping Beauty癌症驱动程序数据库(SBCDDB,),该数据库可识别单个肿瘤或肿瘤群体中的驱动程序。对于这项工作而言,SBCDDB独有,它利用一种可扩展的统计分析方法,使数据可以按不同的生物学特性进行分组。这允许在不同的环境下评估(和重新评估)SB驱动程序。 SBCDDB提供突出显示转座子诱变的空间属性的可视化表示,并将此功能与基因集分析相结合,使用户可以查询驱动程序之间的关系。 SBCDDB是强大的资源,可与人类癌症基因组数据集进行比较肿瘤基因组分析,从而确定驾驶员的优先级。

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