Multiplexing methods to reduce sequencing costs

PROJECT SUMMARY Next-generation sequencing (NGS) technology has enabled significant discoveries and clinical applications from genotype data. In particular, rapid shallow whole genome sequencing (WGS) and whole exome sequencing (WES) has the capacity to revolutionize healthcare interventions. The demand for shallow WGS and WES has exploded and is expected to continue to increase. However, despite the advancements in instrumentation, the marginal cost of shallow WGS and WES has plateaued due to inefficient methods of sample preparation and simplistic approaches to sample pooling. Moreover, the turnaround time of several weeks for sequencing results presents a significant barrier for wide adoption of the technology for clinical purposes. Coral Genomics is developing a new rapid shallow sequencing technology for massively parallel WGS and WES, providing clinically relevant predictions within hours of sequencing completion. We have developed a new sample pooling approach capable of sequencing hundreds of samples with less than 1 week of wait time. With our approach, we have reduced sequencing costs by 50%. With continued development of our library preparation strategy, we expect to further increase the scale of sample processing while also further reducing costs. We have also developed a real-time analysis platform capable of returning variant calls within 2 hours of sequencing completion. Our proprietary dataset associating genetic variations to drug response predictions, developed in- house, is the largest in existence and has led to several new polygenic predictions. With this dataset and our synergistic technologies, we are in the unique position to develop a platform for extremely rapid feedback on clinical samples on a large scale at significantly reduced cost. We expect to bring the cost of shallow coverage WGS and WES down to $15 or less per sample, while providing extremely rapid turnaround times. Specifically, we have a strong foundation for identifying polygenic-score based indications for inflammatory bowel disease, pain medications, and coronary artery disease, and predicting optimal therapeutic intervention in these cases. Successful completion of this project will produce a commercially viable and highly competitive NGS service that is positioned to revolutionize personalized health care.NARRATIVE The ability to sequence DNA has provided us with a molecular microscope to diagnose, determine mechanisms, and design precision therapeutics. Sequencing costs and utility have begun to plateau in the past few years for clinically relevant applications. Coral Genomics is further developing our service to decrease costs and increase the utility of clinical sequencing with a novel pooling strategy, novel clinical predictions, substantial cost savings, and rapid turnaround time.