Integrated software application for management of Hepatitis C Virus data

用于管理丙型肝炎病毒数据的集成软件应用程序

• 批准号: 8253100
• 负责人: Johanna C Craig
• 金额: $ 69.24万
• 依托单位: GATACA, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-19 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253100
• 关键词: Address; Affect; Algorithms; Amino Acid Sequence; Amino Acids; Basic Science; Bioinformatics; Biological; Clinical Trials; Computer software; Data; Data Storage and Retrieval; Database Management Systems; Databases; Development; Disease; Drug Combinations; Drug resistance; Entropy; Environment; Evolution; Funding; Generations; Generic Drugs; Genes; Genetic; Genetic Heterogeneity; Genetic Recombination; Genome; Genomics; Genotype; Goals; Graph; Hepatitis C virus; Heterogeneity; Housing; Informatics; Information Sciences; Internet; Laboratories; Laboratory Research; Lead; Link; Marketing; Mathematics; Measurement; Modeling; Mutation; Mutation Analysis; Nucleotides; Online Systems; Operating System; Output; Patients; Performance; Pharmaceutical Preparations; Phase; Phylogenetic Analysis; Phylogeny; Polymerase; Positioning Attribute; Procedures; Reporting; Research; Research Personnel; Running; Scientist; Security; Services; Sorting - Cell Movement; Structure; System; Technology; Testing; Time; Trees; United States National Institutes of Health; Validation; Variant; Viral; Viral Genes; Virus; Virus Replication; Work; base; chronic liver disease; computerized data processing; data management; design; effective therapy; falls; flexibility; graphical user interface; improved; innovation; middleware; novel; pressure; programs; prototype; repository; resistance mutation; software systems; tool; virus genetics

DESCRIPTION (provided by applicant): The hepatitis C virus (HCV) infects approximately 4 million people in the U.S, and 170 million people worldwide. The high mutation rate of HCV results in vast numbers of new genetic sequences and associated biological data in the daily conduct of laboratory research and clinical trials with attendant serious data management problems. Investigators currently rely upon in-house developed databases, generic software products, and tools from public web repositories to sort, organize and analyze their genomic and biological data. These tools are not tailored to the HCV genome, and moving data from one program to the next is labor intensive and vulnerable to error. We are developing a web-based (vs. local server only) software product tailored for the rapid, efficient and flexible management of HCV data. The product consists of graphical-user interface (GUI) tools and a data-storage and retrieval system that are both designed specifically for HCV analysis. It also includes a commercial relational data base engine. The most notable technical innovation is our annotation tool which simplifies the capture, storage and management of crucial experimental data points, and brings these user defined data points (annotations) into the same searchable context as those that are inherently systemic and structured. Other innovations include our alignment, phylogenetics and mutation analysis tools that are specifically tailored to the mathematics of the HCV replication rate and its error-prone polymerase. In preliminary and Phase I work we designed, built and successfully unit tested a prototype software system, consisting of 3 tiers; presentation (GUI), middleware (Domain), and a relational database management system (RDBMS), and including tools for conducting HCV- tailored alignments and contig assemblies that are linked to a highly flexible query tool, as well as tools for assembling and viewing phylogenic trees and for producing graphics tool that present the raw electropherogram data (traces), and assemble line and bar graphs to plot up to two variables. In this Phase II work, we will develop additional tools for mutation tracking, report generation and entropy measurement, and we will develop statistical routines and security and installation packages. Specific Aims: Aim I. Transition the software platform to cloud computing and hosting environment; Aim II. Develop a suite of tools for conducting full mutation analysis; Aim III. Develop statistical routines; Aim IV. Unit test the software application. We are seeking funds to build our product, addressing a scientific need with a marketable bioinformatics approach. In this way, we will merge informatics with basic research for rapid discovery. We believe that our disease-specific software products will aid in the rapidly developing market of HCV research. The result will be software that greatly improves analysis capabilities and reduces data processing time. These goals fall well within the scope of the NIH to promote basic research in the field of bioinformatics and information sciences, and could lead to enormous public benefit. PUBLIC HEALTH RELEVANCE: The hepatitis C virus (HCV) is difficult to study and not effectively treated with the current anti- viral drug combination. Effective treatment options are years away. A major problem that HCV investigators must contend with is the rapid mutation rate of the viral genes, which creates a need to test patients continuously and a massive data accumulation problem. We are developing a powerful, game-changing software application that will make it easier for scientists to overcome these problems and focus on treatment and cure discovery.

描述（由申请人提供）：丙型肝炎病毒 (HCV) 在美国感染了大约 400 万人，在全世界感染了 1.7 亿人。 HCV的高突变率导致日常实验室研究和临床试验中产生大量新的基因序列和相关生物数据，随之而来的是严重的数据管理问题。研究人员目前依靠内部开发的数据库、通用软件产品和公共网络存储库的工具来分类、组织和分析他们的基因组和生物数据。这些工具并非针对 HCV 基因组量身定制，将数据从一个程序转移到下一个程序需要大量劳动力且容易出错。我们正在开发一种基于网络（相对于仅本地服务器）的软件产品，专为快速、高效和灵活的 HCV 数据管理而定制。 该产品由图形用户界面 (GUI) 工具以及数据存储和检索系统组成，两者都是专为 HCV 分析而设计的。它还包括一个商业关系数据库引擎。最显着的技术创新是我们的注释工具，它简化了关键实验数据点的捕获、存储和管理，并将这些用户定义的数据点（注释）带入与本质上系统性和结构化的数据点相同的可搜索上下文中。其他创新包括我们的比对、系统发育和突变分析工具，这些工具是专门针对 HCV 复制率及其易错聚合酶的数学而定制的。在初步和第一阶段的工作中，我们设计、构建并成功地对原型软件系统进行了单元测试，该系统由 3 层组成；演示文稿 (GUI)、中间件 (Domain) 和关系数据库管理系统 (RDBMS)，包括用于进行 HCV 定制比对和重叠群组装的工具，这些工具链接到高度灵活的查询工具，以及用于组装和查看系统发育树的工具，以及用于生成显示原始电泳图数据（迹线）的图形工具，以及组装线图和条形图以绘制最多两个变量的工具。 在第二阶段的工作中，我们将开发用于突变跟踪、报告生成和熵测量的附加工具，并且我们将开发统计例程以及安全和安装包。具体目标： 目标一、将软件平台过渡到云计算和托管环境；目标二。开发一套用于进行全面突变分析的工具；目标三。制定统计程序；目标四。对软件应用程序进行单元测试。我们正在寻求资金来构建我们的产品，通过适销对路的生物信息学方法来满足科学需求。通过这种方式，我们将信息学与基础研究结合起来，以实现快速发现。我们相信，我们的特定疾病软件产品将有助于快速发展的丙型肝炎研究市场。其结果将是软件大大提高分析能力并减少数据处理时间。这些目标完全属于美国国立卫生研究院促进生物信息学和信息科学领域基础研究的范围，并可能带来巨大的公共利益。 公共卫生相关性：丙型肝炎病毒 (HCV) 很难研究，并且当前的抗病毒药物组合无法有效治疗。有效的治疗方案还需要数年时间。 HCV研究人员必须应对的一个主要问题是病毒基因的快速突变率，这产生了对患者进行持续测试的需要以及大量数据积累的问题。我们正在开发一款强大的、改变游戏规则的软件应用程序，它将使科学家更容易克服这些问题并专注于治疗和治愈方法的发现。