The objective of this proposal is to further optimize Sequencing By Synthesis (SBS) chemistry to power a highly-sensitive, low-cost, sequencing system for clinical diagnostic sequencing called PinPoint MINI. A single human exome at 30 x coverage will be sequenced on this system for less than $150 on an instrument that will sell for under $70,000. The system can run 1-20 samples in parallel generating up to 20 million reads per sample with random sample access in the instrument. Currently, there is no other system on the market which would offer comparable features and performance. The simplicity of the proposed sample preparation and the low cost will enable human exome or targeted sequencing to be widely performed in the clinic and will lead to the revolution in healthcare. This Phase II project has two overall goals: 1) improving sequencing performance (read length and quality) 2) improve sequencing speed. High quality is important to produce more reliable and failsafe genetic diagnostic information and high speed is important to deliver results to physicians and patients quickly. During Phase 2, we will optimize the speed and performance to achieve at least 150 bp read length and reduces our current cycle time to 10 minutes. In addition, we will optimize our novel SBS-walking technology to achieve at least 300 (2 x 150) bp read lengths. Dr. Jeremy Edwards's at the University of New Mexico Health Sciences Center will perform external validation for our sequencing chemistry and systems.
Ultimately, the ability to produce very inexpensive gene expression and detailed DNA sequence information related to cancer will lead for a much wider use of expression and sequence analyses for research and treatment of this devastating disease. In addition, the ability to analyze complex organisms'genomes at a very low cost will both lead to accelerated discoveries throughout biology and provide the basis for Pharmacogenomics, a new paradigm in therapeutics wherein medicines are prescribed based on individual genotypes rather than just observed symptoms.