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

开发综合罕见病生物信息学资源以确定表型与基因型的相关性

基本信息

批准号：
10685889
负责人：
Elizabeth Ottinger
金额：
$ 170.65万
依托单位：
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10685889
关键词：
3-Dimensional Algorithms Animal Disease Models Animal Model Biological Biomedical Computing Chemistry Clinical Data Computational Science Custom Data Data Analyses Data Collection Data Correlations Data Sources Databases Deficiency Diseases Development Disease Disease Pathway Farber&apos s lipogranulomatosis Gene Mutation Genes Genetic Genetic Diseases Genomics Genotype Human Information Centers Laboratories Literature Manuals Methodology Modeling Molecular National Cancer Institute National Center for Advancing Translational Sciences Natural Language Processing Phenotype Procedures PubMed Publishing Rare Diseases Resources Signal Transduction Software Framework Source Therapeutic Therapeutics for Rare and Neglected Diseases Training Variant Visual Visualization software Work analytical tool anticancer research bioinformatics resource creatine transporter genetic variant insight interest programs protein structure text searching web app web interface

项目摘要

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. The team made progress towards the upcoming release of version 1 of the RARe-SOURCE / Rare Disease Bioinformatics Resource web application. Information has been integrated 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 and gene mutations. 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. Efforts are being made toward incorporating natural language processing (NLP) models and training text mining algorithms to mine PubMed for rare disease gene variant associations in the development of RARe-SOURCE. Work also has been initiated to incorporate rare disease animal model modules. The team is establishing a comprehensive standard operating procedure and methodology for accessing and incorporating genomic variant and clinical data from non-public databases and sources.

TRND计划以前从事过两种罕见的疾病，即肌酸转运蛋白缺乏症（CTD）和Farber疾病（FD），用于初步开发此综合生物信息学资源。在此期间，合作团队从现有的生物学信息来源中捕获了疾病，途径，基因和化学水平的CTD和FD数据，包括与变异相关的表型信息。该团队利用并调整了现有的ABCS资源，以构建用于数据收集和分析的软件框架，实施分析和可视化工具，以易于消化的方式显示收集的信息。该团队在即将发布的稀有源 /稀有疾病生物信息学资源Web应用程序的版本第1版方面取得了进展。信息已从遗传和罕见疾病信息中心（GARD）和NCATS疾病协调数据库中进行了整合，以允许搜索任何罕见的感兴趣疾病。在Web界面中纳入了一些应用，以提供有关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，并适用于Web应用程序，以允许对2D/3D蛋白结构和基因突变的详细视觉效果和交互式探索。此外，所有关于CTD/SLC6A8和FD/ASAH1基因数据的已发表的，手动策划的文献均已完全集成，以提供高精度基因型 - 表型相关数据。正在为合并自然语言加工（NLP）模型和培训文本挖掘算法而努力，以在稀有源中开发稀有疾病基因变异关联。还已经开始进行工作以结合稀有疾病动物模型模块。该团队正在建立一个全面的标准操作程序和方法，用于访问和合并非公共数据库和来源的基因组变体和临床数据。