Phase I Amount
$1,000,930
Undiagnosed diseases clinics and newborn intensive care unit rapid genome sequencing programs have emerged as the primary settings for diagnosing patients with complex phenotypes. Subspecialty clinics, pharmaceutical companies, and direct-to-consumer genetic testing companies are increasingly adopting these technologies for diagnosing patients, or studying disease with the goal of developing treatments. In all cases, a diagnostic, or research analysis approach based on comprehensive genomic sequencing data, and, crucially, collaborative analysis by expert teams has been adopted. The team-based approach leverages the expertize of a wide array of specialists, for example, the physician's knowledge of the patient's phenotypes and family history; the medical geneticist's knowledge of genetic diseases; the bioinformatician's and variant scientist's expertise in interpreting the potential diagnostic role of individual genetic variants; the genetic counselors expertize in synthesizing all available data, and coordinating with patients, families and treating physicians. A patient's phenotypes, and more frequently, the myriad sources of evidence used to support the diagnostic role of variants, genes, and their associations with disease evolve over time, and consequently research and diagnostic analysis is a long-term process. Existing tools focus on analysis at a single point in time, and require over-burdened genetic counselors to manually evaluate cases for changes, or miss the opportunity for diagnosis due to a lack of evidence at the time of evaluation. Here, we propose to build a commercial software system to address two pressing needs faced by consumers of genomic sequencing data. First, a complete end-to-end bioinformatic pipeline to process raw sequencing data to lists of prioritized genetic variants, and structural variant calls, which explicitly includes an automated (or manually triggered) data re-analysis pipeline to support long-term genomic care. Second, a comprehensive, versatile, and yet easy-to-use visualization platform will seamlessly display all genomic data and metadata to the analysis teams in web applications custom designed to address the needs of the diverse experts collaborating on these projects. We will evaluate and refine this product in our undiagnosed diseases clinic and our newborn intensive care unit, ideal settings to garner critical feedback and suggestions from teams representative of the initial target market for this tool.
Public Health Relevance Statement: Narrative We are building a complete, commercial software solution to enable team-based genomic analysis in all settings, including, but not limited to, challenging diagnostic cases in undiagnosed diseases clinics and rapid sequencing programs in newborn intensive care units. Our software will include secure computational pipelines to process genomic data that can be deployed on the cloud, or on institutional hardware, and visual data portals that make access to, and analysis of, this data available to all. We will evaluate and refine these tools in team-based settings in the NHGRI funded Undiagnosed Diseases Network clinical site, and newborn intensive care unit at the University of Utah.
Project Terms: Caring; Custom; Painful; Variant; Medical; On-Line Systems; online computer; web based; customs; Variation; portability; Orphan Disease; Rare Disorder; orphan disorder; Genomics; cohort; Modeling; Institution; Bioinformatics; Pharmacologic Substance; National Human Genome Research Institute; Rare Diseases; member; drug development; Metadata; Data; Communication Tools; clinical research site; scale up; design; Security; genetic variant; Update; software systems; Address; Process; genome sequencing; data sharing portal; computational infrastructure; Gene variant; allele variant; allelic variant; genomic variant; designing; entire genome; full genome; data management; experience; Disorder; Ensure; Evaluation; Scientist; tool; restraint; Notification; Adopted; interest; Funding; Diagnostic; Investigation; Services; Complex; Clinic; Genetic Services; Knowledge; Source; programs; Intuition; Visual; Individual; Collaborations; online app; web application; web based app; web based application; genomic data-set; genomic dataset; Software; meta data; amateur science; amateur scientists; citizen scientists; civic science; crowd science; crowd-sourced science; scientific citizenship; NHGRI; National Center for Human Genome Research; genetic condition; genetic disorder; clinical site; social role; Diagnosis; Foundations; Community Hospitals; Environment; Manuals; Marketing; Goals; Disease; Pain; Genes; Genome; Algorithms; Family; Patients; Feedback; Phenotype; Recording of previous events; Neonatal Intensive Care Units; Online Systems; Physicians; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; History; histories; Newborn Intensive Care Units; neonatal ICU; Bio-Informatics; genetic counselor; Genetic Diseases; assess effectiveness; cloud based; bio-informatics pipeline; internet based platform; internet platform; web based platform; web based system; web enabled platform; gene testing; gene-based testing; intuitive; Time; Research; mosaic; Communities; Visualization; computational pipelines; critically ill newborn; Role; user-friendly; citizen science; data portal; whole genome; bioinformatics pipeline; web platform; genetic testing; computer infrastructure; web app; genomic data; analysis pipeline; data sharing; Secure; Privacy; Quality Control; Computer software; support tools; effectiveness evaluation; Specialist; Universities; Utah; Standardization; Suggestion; Technology; determine effectiveness; effectiveness assessment; evaluate effectiveness; examine effectiveness
