Integrated software application for management of Hepatitis C Virus data

描述(申请人提供)：丙型肝炎病毒(丙型肝炎病毒)在美国感染约400万人，在全球感染1.7亿人。丙型肝炎病毒的高突变率导致在日常的实验室研究和临床试验中产生大量新的基因序列和相关的生物数据，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储存库的工具来分类、组织和分析他们的基因组和生物数据。这些工具不是为丙型肝炎病毒基因组量身定做的，而且将数据从一个程序转移到另一个程序是劳动密集型的，而且容易出错。我们正在开发一种基于网络(仅限本地服务器)的软件产品，专为快速、高效和灵活地管理丙型肝炎病毒数据而定制。该产品包括专门为丙型肝炎病毒分析设计的图形用户界面(GUI)工具和数据存储和检索系统。它还包括一个商业关系数据库引擎。最值得注意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)与那些固有的系统性和结构化的数据点(注释)放入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，这些工具专门针对丙型肝炎病毒复制率及其容易出错的聚合酶的数学模型量身定做。在初步和第一阶段工作中，我们设计、构建并成功地对原型软件系统进行了单元测试，该原型软件系统由三层组成：表示(图形用户界面)、中间件(域)和关系数据库管理系统(RDBMS)，其中包括用于进行丙型肝炎病毒定制的比对和连接到高度灵活的查询工具的重叠群组装的工具，以及用于组装和查看系统发育树的工具，以及用于生成呈现原始电泳图数据(轨迹)的图形工具，并组装线图和条形图以绘制多达两个变量。在这项第二阶段的工作中，我们将开发更多用于突变跟踪、报告生成和熵测量的工具，我们将开发统计例程以及安全和安装包。具体目标：AIM一.将软件平台过渡到云计算和托管环境；AIM二.开发一套进行全面突变分析的工具；AIM三.开发统计例程；AIM四.单元测试软件应用程序我们正在寻求资金来建造我们的产品，用一种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，我们将把信息学与基础研究结合起来，以实现快速发现。我们相信，我们针对疾病的软件产品将有助于快速发展的丙型肝炎研究市场。其结果将是极大地提高分析能力和减少数据处理时间的软件。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。

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.