Informatics Tools for High-throughput Analysis of Cancer Mutations

 描述（由申请人提供）：癌症测序项目已经确定了大量的突变，其癌症相关性尚不清楚。为了满足这一需求，我们的团队开发了一个应用程序，用于癌症突变的高通量计算分析。该应用程序- CRAVAT/MuPIT -在一次批量上传中接受数百万个突变，它被设计成一个漏斗，这样用户就可以将测序项目中发现的大量突变缩小到最有可能提供信息的数量。该系统使得能够组合多个度量以生成优先化列表。这些功能包括突变调用的质量控制，突变后果类型，生物信息学评分以识别致病性和驱动突变，群体等位基因频率，肿瘤组织类型中的先前发生，相关文献的指针和注释蛋白质结构的交互式可视化，包括来自21种TCGA肿瘤类型的生物学重要位置，突变和突变热点的可定制视图。CRAVAT/MuPIT应用程序已经通过网络界面提供了21/2年。在此期间，来自六大洲（北美、南美、欧洲、亚洲、澳大利亚和非洲）88个国家的6，056名独立用户提交了分析工作。我们总共处理了12,051个任务，从几个突变到超过6200万个。总的来说，该应用程序已经处理了超过6.73亿个突变。（资料来源：Google Analytics）我们吸引了一个用户社区，涵盖基础和临床癌症研究人员，他们都依赖于高通量肿瘤测序。为了满足我们社区未来的需求，我们将扩展我们应用程序的功能，以更全面地支持非编码突变的分析，识别突变与药物反应之间的关联，以及基于路径的突变影响解释。我们将投入大量努力，确保我们的工具与其他信息学服务可互操作，可以在云环境中运行，也可以在本地安装的管道中运行，以支持受保护的数据。

 DESCRIPTION (provided by applicant): Cancer sequencing projects have identified a very large number of mutations whose cancer relevance is not yet understood. To address this need, our team has produced an application for high-throughput computational analysis of cancer mutations. The application -- CRAVAT/MuPIT -- accepts millions of mutations in a single batch upload, and it is designed to work as a funnel, so that users can narrow down a very large number of mutations discovered in a sequencing project to a tractable number of those most likely to be informative. The system enables combination of multiple metrics to generate a prioritized list. Metrics include quality control of mutation calls, mutation consequence types, bioinformatic scores to identify pathogenic and driver mutations, population allele frequencies, previous occurrence in tumor tissue types, pointers to relevant literature and interactive visualization on annotated protein structures, including customizable views of biologically important positions, mutations and mutation hot spots from 21 TCGA tumor types. The CRAVAT/MuPIT application has been available through a web interface for 21/2 years. In that time, analysis jobs have been submitted by 6,056 unique users from 88 countries on six continents (North America, South America, Europe, Asia, Australia and Africa). We have processed a total 12,051 missions, ranging from a few mutations to over 62 million. In total, the application has processed over 673 million mutations. (Source: Google Analytics). We have attracted a user community that spans both basic and clinical cancer researchers, all of whom rely on high-throughput tumor sequencing in their work. To address the needs of our community going forward, we will extend the functionality of our application to more fully support analysis o non-coding mutations, identification of associations between mutations and drug response, and pathway-based interpretation of mutation impact. We will dedicate substantial effort to ensure that our tools are interoperable with other informatics services, can be run in cloud environments and can be run in locally-installed pipelines to support protected data.