A Community Driven Framework for Genome Based Clinical Diagnostics

 描述(申请人提供)：来自下一代测序技术的个人基因组序列正在通过诊断测试渗透到临床护理中。临床实验室面临着以明确、可重复的方式处理这些数据的压力，并提供在不同测试地点具有可比性的解释，但要做到这一点面临许多困难。完毕 在过去的几年里，“变异文件”已经成为交换和分析个人基因组序列的通用货币，用于研究，现在也用于临床目的。这些文件描述了个人基因组中与参考GenBank基因组序列不同的每个位置。鉴于它们的广泛使用，变体文件是设计适合临床应用的格式的一个合乎逻辑的起点。目前变异文件的样式差异很大，复杂变异的注释方式并不统一，基因组学还没有接受医学数据标准的使用。意识到这些问题的诊断基因组学社区已经动员了一个工作组来提供建议和要求，以统一变异注释，以改善公共卫生和临床应用。例如，如果没有获取变异序列数据的明确标准，以下应用程序的数据共享就会受到阻碍：跨实验室进行质量保证，拥有用于解释的数据库，以及用于未来使用的患者记录。该建议通过提供新的算法来定义序列变体，并利用临床诊断界的指导，开发文件格式和软件来传达该信息，从而解决了多态变体描述的问题。标准化格式VCFclin和共同开发的软件工具将结束基因组数据从测序机流经变量调用和分析管道到解释和临床使用时的信息丢失和模棱两可。

 DESCRIPTION (provided by applicant): Personal genome sequences from next generation sequencing technologies are permeating clinical care via diagnostic testing. Clinical labs are under pressure to handle this data in unambiguous, reproducible ways, and provide interpretations that are comparable across testing sites, but face many difficulties to do so. Over the last several years the 'variant file', has emerged as the common currency for exchange and analyses of personal genome sequences for research, and now clinical purposes. These files describe every position in a personal genome that differs from the reference GenBank genome sequence. Given their widespread use, the variant file is a logical starting point for designing a format suitable for clinical applications. Currently variant file styles are widely divergent, ther is not uniformity in the way that complex variants are annotated and genomics has not embraced the use of medical data standards. The diagnostic genomics community, aware of these issues, has mobilized a working group to provide recommendations and requirements to unify variant annotation, to improve public health and clinical applications. For example, without clear standards for capturing variant sequence data, sharing data for the following applications is hindered: across laboratories for quality assurance, with databases for making an interpretation, with a patient record for future use. This proposal addresses the problems with polymorphic variant description by providing novel algorithms to define sequence variants and by developing file formats and software to communicate this information, using guidance from the clinical diagnostic community. The standardized format, VCFclin, and co-developed software tools will end information loss and ambiguity as genomics data flow from sequencing machines, through variant calling and analysis pipelines to interpretation and clinical use.