iGenomeTM Software Platform Prototype for Individual Genetic Health Assessment

描述（由申请人提供）：充分的一般临床知识、DNA测序技术和对2，600多个人类基因的遗传突变的理解可以支持开始将个体基因组序列整合到许多医学专业的临床实践中。随着2007年新的DNA测序技术的部署，允许对临床感兴趣的基因组子集的个体基因组序列进行具有成本效益的询问，对患者护理的快速影响的潜力是显而易见的。然而，缺乏合适的人类基因组分析和解释平台是一个实质性的障碍，随着这些新的测序技术的采用，这将减缓实施。为了解决这一差距，我们计划创建一个商业软件平台，支持个人人类基因组序列的输入、分析、存储和报告，为核苷酸序列属性提供遗传健康评估，这些属性可能是资产或负债，具体取决于临床背景。这项为期16个月的SBIR I期提案将支持能够支持协作研究的软件原型的开发，并将汇编我们的第一项试点研究所需的信息，即基于其对人类系统生物学早期研究的适用性（可能具有快速临床实用性）选择的止血和血栓形成临床领域的个体基因组分析。在第一阶段的努力中要解决的挑战是首先开发能够高度准确，自动化识别，提取和有序存储个人的人类变异数据的应用程序，然后根据先前表征的人类突变和与遗传性疾病相关的变异的知识库对这些变异进行测试。其他挑战将是将表型和突变信息结构化为对研究人员和临床医生有用的格式。第一阶段工作的成功完成将导致从个体基因组序列数据中全面鉴定DNA序列变异，并确定性能指标，这些指标将在第二阶段进行扩展，用于能够每天处理至少100个个体基因组的目标的商业软件平台开发。这项工作的影响将是最初促进人类系统生物学研究，这些研究将展示如何将这些结果用于诊断，预后和个性化治疗计划的开发，并最终支持诊断程序。软件原型和商业级软件的首次发布将在未来五年内为将个性化医疗带到床边做出关键贡献。公共卫生相关性：我们对遗传对疾病和健康的贡献的知识是多方面的，形成了广泛的范围;然而，要将这些知识直接应用于改善健康和影响患者护理，产生个人人类基因组序列数据，分析数据并将结果制定为有意义的报告的方法需要复杂的软件和信息系统，目前还不存在。我们建议开发的软件和信息技术将有助于理解个体遗传变异及其在诊断、确定疾病预后和选择个性化治疗方案方面的应用。计算结构化知识和个体基因组数据的潜在应用可以应用于医学的每个治疗领域和分支;这项工作补充了生物医学信息科学和技术倡议（BISTI），并有力地支持了美国国立卫生研究院的路线图目标。

DESCRIPTION (provided by applicant): Sufficient general clinical knowledge, DNA sequence technology and understanding of genetic mutations for over 2,600 human genes can support beginning the integration of individual genome sequence into clinical practice for a number of medical specialties. With the 2007 deployment of novel DNA sequence technologies that permit cost-effective interrogation of individual genome sequence for the subset of the genome of clinical interest, the potential for rapid impact on patient care is palpable. However, the lack of a suitable human genome analysis and interpretation platform is a substantial barrier that will slow implementation as these new sequence technologies are adopted. To address this gap, we plan to create a commercial software platform supporting the input, analysis, storage and reporting of individual human genome sequence providing a genetic health assessment for nucleotide sequence attributes that may be either assets or liabilities depending on clinical context. This sixteen- month SBIR Phase I proposal will support the development of a software prototype capable of supporting collaboration studies and will compile the information necessary for our first pilot study, individual genome analysis for the Hemostasis and Thrombosis clinical area selected based on its suitability for early studies in human systems biology that would potentially have rapid clinical utility. The challenges to be addressed in the phase I effort are first to develop applications capable of highly accurate, automated identification, extraction and ordered storage of individual human variation data followed by the testing of these variations against a knowledgebase of previously characterized human mutations and variations associated with heritable diseases. Additional challenges will be to structure phenotypic and mutation information into formats useful to researchers and clinicians. Successful completion of the phase I effort will result in comprehensive identification of DNA sequence variation from individual genome sequence data and the determination of performance metrics that will be feasible to scale in phase II for the commercial software platform development capable of processing a target minimum of 100 individual genomes per day. The impact of this work will be to initially facilitate human systems biology studies that will demonstrate how such results can be utilized for diagnosis, prognosis and development of personalized therapeutic plans and ultimately, support diagnostic procedures. The software prototype and the first release of the commercial grade software will make key contributions to bringing personalized medicine to the bedside in the next five years. PUBLIC HEALTH RELEVANCE: Our knowledge of genetic contributions to disease and health is multifaceted and forms a broad spectrum; however, to apply this knowledge directly to improve health and impact patient care, the means to produce individual human genome sequence data, analyze the data and formulate the results into meaningful reports requires complex software and information systems which do not yet exist. The software and information technologies we propose to develop will contribute to the understanding of individual genetic variation and it application for diagnostics, determining disease prognosis and for selecting individualized treatment programs. Potential application of computationally structured knowledge and individual genome data can be applied across every therapeutic area and branch of medicine; this work complements the Biomedical Information Science and Technology Initiative (BISTI) and strongly supports the National Institutes of Health RoadMap objectives.