A Community Driven Framework for Genome Based Clinical Diagnostics

 描述（由申请人提供）：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，并提供在各检测中心之间具有可比性的解释，但这样做面临着许多困难。超过 在过去的几年中，“变体文件”已经成为用于研究和现在临床目的的个人基因组序列的交换和分析的通用货币。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。鉴于其广泛使用，变体文件是设计适合临床应用的格式的逻辑起点。目前，变异文件的风格是千差万别的，没有统一的方式，复杂的变异注释和基因组学还没有接受使用的医疗数据标准。诊断基因组学界意识到这些问题，已经动员了一个工作组来提供统一变异注释的建议和要求，以改善公共卫生和临床应用。例如，由于没有捕获变异序列数据的明确标准，以下应用的数据共享受到阻碍：跨实验室进行质量保证，数据库进行解释，患者记录供将来使用。该提案通过提供新的算法来定义序列变体，并通过开发文件格式和软件来传达此信息，使用临床诊断界的指导来解决多态性变体描述的问题。标准化格式VCFclin和共同开发的软件工具将结束信息丢失和模糊性，因为基因组学数据从测序机通过变异调用和分析管道流向解释和临床使用。

 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.