Developing an Integrated Rare Disease Bioinformatics Resource to Determine Phenotype to Genotype Correlations

TRND计划之前研究过的两种罕见疾病，肌酸转运蛋白缺乏症（CTD）和法伯病（FD），正在用于这种综合生物信息学资源的初步开发。在此期间，合作团队从现有的生物信息源中获取了疾病、途径、基因和化学水平的CTD和FD数据，包括变异相关表型信息。该团队利用并调整了现有的ABCS资源，构建了一个用于数据收集和分析的软件框架，实现了分析和可视化工具，以易于理解的方式显示收集到的信息。在完成罕见源/罕见病生物信息学资源web应用程序方面取得了进展，包括整合来自遗传和罕见病信息中心（GARD）和NCATS疾病协调数据库的罕见病信息，以便对任何感兴趣的罕见病进行搜索。几个应用程序被整合到web界面中，以提供与罕见疾病相关的任何基因的高级概述。可视化工具是定制的，并适应于web应用程序，允许详细的视觉效果和2D/3D蛋白质结构的交互式探索。此外，所有已发表的、人工整理的关于CTD/SLC6A8和FD/ASAH1基因数据的文献被完全整合，以提供高精度的基因型-表型相关数据。

Two rare diseases that the TRND program has worked on previously, Creatine Transporter Deficiency (CTD) and Farber Disease (FD), are being used for the initial development of this integrated bioinformatics resource. During this period, the collaborative team captured CTD and FD data at the disease, pathway, gene, and chemistry levels, including variant-related phenotypic information, from existing biological informational sources. The team leveraged and adapted existing ABCS resources to build a software framework for data collection and analysis, implementing analytical and visualization tools to display the collected information in an easily digestible manner. There was progress towards the completion of the RARe-SOURCE / Rare Disease Bioinformatics Resource web application, including integration of rare disease information from the Genetic and Rare Diseases Information Center (GARD) and the disease harmonization database at NCATS to allow searches of any rare disease of interest. Several applications were incorporated into the web interface to provide a high-level overview on any gene associated with a rare disease. Visualization tools were customized and adapted to the web application to allow detailed visuals and interactive exploration of 2D/3D protein structures. Additionally, all published, manually curated literature on CTD/SLC6A8 and FD/ASAH1 gene data was fully integrated to provide high accuracy genotype-phenotype correlation data.