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

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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.