Genboree System for Translational Studies of Genome Variation

描述（由申请人提供）：我们建议开发Genboree系统，以实现任何规模的基因组变异的协作翻译研究。通过采用信息技术的创新组合，如生命科学标识符，XML，分布式注释系统和网络服务，Genboree将最大限度地减少跨学科研究小组（包括临床医生，生物学家和基因组科学家）合作的技术障碍。两个独立的NIH资助的项目，“非综合征性听力障碍基因的识别”（“NSHI”）和“癫痫中离子通道的平行序列分析”（“癫痫”）将被用来推动Genboree软件的开发和增强其可用性。Genboree系统将使研究复杂但流行的疾病，如NSHI和癫痫的遗传易感性因素成为可能。通过这些努力，对基因组变异的致病模式有了更好的理解，将产生预测和诊断测试，并有助于阐明病理机制。对机制的理解将反过来指向疾病预防的手段和治疗干预的目标。这项研究计划有可能推动世纪的医学从诊断和治疗到预测和预防的范式。该研究计划面临的主要信息学挑战之一是临床和基因组信息的整合。另一个挑战是整合临床医生、生物学家和基因组科学家的协作努力。另一个挑战是处理基因组变异信息洪流所需的极端可扩展性，这些信息将超过过去基因组计划产生的数量级。目前，这三项挑战都没有得到充分解决。本提案的总体目标是通过开发Genboree系统应对这些挑战。Genboree原型最初开发用于支持贝勒医学院人类基因组测序中心的协作基因组注释和比较基因组项目。Genboree的关键特征之一是通过将任何实验或计算得出的数据元素以注释的形式投影到参考基因组序列上，使用组装的基因组序列作为参考来整合数据的能力。由于内置的访问控制功能，Genboree符合HIPAA标准，因此能够整合患者信息和从患者样本中获得的基因组信息。在当前Genboree原型的基础上，将开发一个系统来整合数据、工具和发现管道，以支持基因组变异的协作翻译研究。

DESCRIPTION (provided by applicant): We propose to develop the Genboree system to enable collaborative translational studies of genome variation on any scale. By employing an innovative combination of information technologies such as Life Science Identifiers, XML, Distributed Annotation System and web services, Genboree will minimize technical barriers to collaboration by interdisciplinary research groups including clinicians, biologists, and genome scientists. Two independently NIH-funded projects, "Identification of Nonsyndromic Hearing Impairment Genes" ("NSHI") and "Parallel Sequence Profiling of Ion Channels in Epilepsy" ("Epilepsy") will be employed to drive development and enhance usability of Genboree software. Genboree system will enable the study of genetic susceptibility factors to complex yet prevalent diseases such as NSHI and Epilepsy. An improved understanding of causative patterns of genome variation that is anticipated to emerge from these efforts will produce predictive and diagnostic tests and will help elucidate pathological mechanisms. The understanding of mechanisms will in turn point to means of disease prevention and to targets for therapeutic intervention. This program of research has the potential to propel the 21st century medicine from a diagnose-and-treat to a predict-and-prevent paradigm. One of the main informatic challenges facing this program of research is the integration of clinical and genomic information. Another challenge is the integration of collaborative efforts involving clinicians, biologists, and genome scientists. Yet another challenge is extreme scalability required to handle the torrent of genome variation information that will surpass by orders of magnitude the amounts generated by genome projects in the past. None of these three challenges are adequately addressed at this time. The general aim of this proposal is to address these challenges through the development of the Genboree system. Genboree prototype was initially developed to support collaborative genome annotation and comparative genomic projects at the Human Genome Sequencing Center at Baylor College of Medicine. One of the key features of Genboree is the ability to integrate data using assembled genome sequences as a reference by projecting any experimentally or computationally derived data elements onto the reference genomic sequence in the form of annotations. Due to built-in .access control features, Genboree is within reach of HIPAA compliance and thus capable of integrating both patient information and the genomic information obtained from patient samples. Building on the current Genboree prototype, a system will be developed to integrate data, tools, and discovery pipelines to support collaborative translational studies of genome variation.