The overarching goal of this exploratory project is to accelerate biomedical innovation and enable personalized medicine in a cost-effective manner. We will achieve that by (1) identifying sweet-spot genomics architectures that are based on existing electronic components and are accessible via conventional programming models, which achieve performance/density/cost that is >10√ó superior to that of commodity architecture, and which can be produced in high volume116, (2) accelerating adoption of these architectures by removing the barriers formed by current software infrastructure117, and (3) developing key algorithms118 and their mappings to the sweet-spot architecture for workflows to be accelerated, including disease-associated variant calling, metagenomics, and de novo assembly.