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Seth McDonald

Illumina, Inc., USA

Title: Improved illumina sequencing by polymerase engineering

Biography

Biography: Seth McDonald

Abstract

The sequencing-by-synthesis (SBS) chemistry commercialized by Illumina has been a key enabler of massively parallel nextgeneration sequencing, which in turn has dramatically reduced the cost of sequencing human genomes and resulted in personalized medicine initiatives and population sequencing efforts throughout much of the world. The capacity of engineered archaeal family B DNA polymerases (pols) to incorporate modifi ed nucleotides has been exploited by researchers throughout academia and biotechnology, including Illumina’s SBS chemistry. Nucleotides with a 3’-reversible terminator and fluorophores attached via the base serve as the basis for base calling in Illumina NGS platforms. Pols deployed on the fi rst Genome Analyzer™ instruments had poor incorporation effi ciency of these modifi ed nucleotides. Through our engineering eff orts, we have facilitated a significant reduction in chemistry time while improving sequencing data quality and enabling over 300 bp read lengths. The critical goal of our research is to engineer pols with enhanced selectivity, fidelity, and incorporation efficiency of modified nucleotides to enable faster sequencing turnaround time and boost adoption of NGS technologies in the clinic.