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，以实现对任何规模的基因组变异的协作性翻译研究。通过采用生命科学识别符、XML、分布式注释系统和网络服务等信息技术的创新组合，Genboree将最大限度地减少包括临床医生、生物学家和基因组科学家在内的跨学科研究小组合作的技术障碍。两个由美国国立卫生研究院独立资助的项目--“非综合征性听力障碍基因的鉴定”(“NSHI”)和“癫痫患者离子通道的平行序列分析”(“Epiepsy”)将用于推动Genboree软件的开发和增强其可用性。Genboree系统将使对NSHI和癫痫等复杂而普遍的疾病的遗传易感因素的研究成为可能。对这些努力预计会出现的基因组变异的致病模式的更好的理解将产生预测性和诊断性测试，并将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。这一研究计划有可能推动21世纪的医学从诊断和治疗转向预测和预防范式。这一研究项目面临的主要信息学挑战之一是临床和基因组信息的整合。另一个挑战是涉及临床医生、生物学家和基因组科学家的合作努力的整合。另一个挑战是处理基因组变异信息洪流所需的极高可扩展性，这些信息的数量将超过过去基因组计划产生的数量的数量级。目前，这三个挑战都没有得到充分解决。这项提案的总体目标是通过开发Genboree系统来应对这些挑战。Genboree原型最初是为了支持贝勒医学院人类基因组测序中心的合作基因组注释和比较基因组项目而开发的。Genboree的关键特征之一是能够使用组装的基因组序列作为参考来集成数据，方法是将任何通过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。由于内置的访问控制功能，Genboree符合HIPAA的要求，因此能够集成患者信息和从患者样本中获得的基因组信息。在目前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合作翻译研究。

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.