An innovative WGS platform for discovery, annotation, and interpretation of all forms of human genetic variation.

PROJECT SUMMARY Modern DNA sequencing technologies have transformed our ability to interrogate human genomes in a single experimentthereby eliminating the inherent blind spots of gene panels and whole exome sequencingFurthermorerecent speed and economy improvements are driving the cost of whole genome sequencingWGSdown to that of WESthereforewe foresee a transition over the next two years to WGS as the de facto test for human disease research and diagnosis in academic labshospitalsand both biotechnology and pharmaceutical companiesIndeedconservative estimates projectmillion human genomes will be sequenced in next decadeHoweverthe transition to research and diagnostics driven by WGS presents a substantial data processing burdenas a single WGS sample represents at leastgigabytes and converting the raw data into a comprehensive set of genetic variation requires an intricaterapidly changingand computationally onerous workflowBased on our history of developing innovative computational methods for genomic research and motivated by the acute need for advancedscalable computing platformsthe applicant team founded BaseGenomicsBaseBasehas created an innovative platform for WGS data processingquality controlvariant detection and prioritizationand data visualization using Amazon Web ServicesAWScloud computingDeveloped in close collaboration with AWS engineersthe fundamental strengths of the Baseplatform are its speedcostcapacity for parallelizationandmost importantlyits ability to accurately identify all forms of genetic variationwhereas most other commercial offerings focus on solely the easiest formsSNPs and INDELsof variation to discoverWe argue thatin order to maximize the researchdiagnosticand pharmacogenetics utility of WGSit is imperative to create a complete catalog of all variation in each sequenced genomeIn this proposalwe will further improve our technologies with the following aimsAimDevelop proprietary technologies for prioritizing and annotating copy number and structural variation via population scale databasesWe have developed STIXSTructural variant IndeXa proprietary compression algorithm and database for efficiently profiling evidence for SV among thousands of human genomesWe propose to leverage this innovation to create uniqueproprietary STIX databasesand an associated SV annotation engine to facilitate accurate prioritization of SV for customer WGS cohortsAimCreate a securehigh performance customer data submission portalWe will develop a secure customer data submission portal that maximizes efficiency and security while allowing customers to upload data and invoke processing through the Baseplatform PROJECT NARRATIVE Modern DNA sequencing technologies have transformed our ability to interrogate human genomes in a single experimentthereby eliminating the inherent blind spots of gene panels and whole exome sequencingHoweverthe transition to research and diagnostics driven by whole genome sequencing presents a substantial data processing burden and converting the raw data into a comprehensive set of genetic variation requires an intricaterapidly changingand computationally onerous workflowThis proposal from baseGenomicsLLC seeks to develop new software and algorithms that empower human genome analysis and interpretation in both diagnostic and research settings