Bioinformatics Section

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ABSTRACT Model organisms are invaluable for understanding the role of genes in human disease and will be key to assessing the impact of millions of specific genetic variants uncovered by high-throughput genome sequencing. The modeling of specific genetic variants is predicated on model organisms engineered using precisely targeted genetic manipulations, careful and accurate variant annotation, and precise phenotyping. The modeling will also require advanced informatics capabilities to integrate variant information across species, support variant nomination and assessment, track model production and associated experimental data via a LIMS system, and to disseminate the information and engage the community via a web portal. Variant information from model organisms may provide insight into the molecular mechanism underlying a phenotype of interest, inform the specific genetic targeting strategy, and influence choice of model organism. As variant annotation resources continue to add information and new resources come online, informatics workflows must be able to accommodate and incorporate them into the model production process. The Bioinformatics Section of the BCM Center for Precision Medicine Modeling will develop these informatics capabilities by leveraging our extensive experience in multi-omic data integration and coordination, cross-species phenotype matching via the MARRVEL system, extension of our KOMP2 LIMS system implementation, and by leveraging key elements of the ClinGen Resource, an FDA-recognized repository for genomic information that we co-developed. By linking human and model information within integrated workflows, the infrastructure will facilitate precision modeling in one direction, and in the other direction will feed model-derived information and knowledge back to the community. By integrating variant resources and providing mechanisms for variant evaluation and information sharing, the Pre- Clinical/Co-Clinical and Disease Modeling Unit will more efficiently develop and evaluate model organisms. Bioinformatics infrastructure will support the variant evaluation process through final variant selection and presentation to the Steering Committee.