Almost all genetic variants have contextual expression and meaning that depend on other genomic sequences and environmental factors interacting through complex regulatory networks. Given the importance of context, the accurate interpretation and effective use of genetic instructions are impossible with only partial access to genetic codes, said Radoje Drmanac of Complete Genomics. Furthermore, each person has 10,000 to 100,000 family-specific genetic variants along with approximately 100 de novo personal variants in addition to a few million population variants. No comprehensive predefined genetic variant chips can be designed to detect such a wide range of variability.

Whole-genome sequencing provides a maximum level of strictly genetic information, Drmanac said. By providing greater understanding of disease, it has the potential to produce greater efficacy, safety, and overall success in drug development.

Whole-genome sequencing has two main areas of application: biological understanding and genomic medicine. Understanding the molecular and genetic bases of thousands of human diseases, developing better targeted drugs and other therapies, including those for disease prevention, and developing personal genome interpretation software will require the sequencing of millions of genomes, Drmanac said. Today perhaps only 10,000 genomes have been sequenced, so developing a true understanding of disease biology requires sequencing on a much larger scale.

The world contains billions of people, Drmanac noted. “If we’re really serious and want to take whole-genome sequencing as the basis for medicine, we need to sequence billions of genomes.” But sequencing on that scale will require that the process be industrialized. Small processes may have benefits for specialized applications, but large-scale massively parallel whole-genome sequencing is needed and this must be designed and optimized to achieve high quality and low cost.

Complete Genomics has been developing a turnkey service that enables customers to outsource whole-genome sequencing. Customers send samples to the company and receive data in return. Furthermore, the data received are not just sequences but the fully assembled genome with an annotated list of informative sequence variants, with each base marked as reference, variant, or a no-call. Each variant has a confidence score to balance sensitivity and specificity, and variations in known protein coding and regulatory gene sequences are identified. Drmanac acknowledged that for medical applications it is necessary to include an interpretation of the data, and Complete Genomics is currently working on developing a system for this purpose.

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