100. Ultrasensitive molecular residue disease detection enabled by genome wide concatemer error correction

Aly Abdelkareem

Paul Tang

Dr Tang co-founded AccuraGen in 2013, together with a group of fellow scientists in the Bay area, to improve rare allele detection in circulating cell-free DNA. Prior to embarking on this venture, Dr Tang was a technical lead at the Genomics Core Facility at University of California, San Francisco (UCSF), where he contributed to an early foundation of Genomics Medicine Initiative at UCSF, led by Dr Bob Nussbaum. From 2010-2013, when he was a postdoc at Dr Pui-Yan Kwok lab at UCSF, he has co-authored more than 10 peer reviewed papers in reputed journals, utilizing a variety of genomic technologies to understand different human diseases. Dr Tang holds a B.S. in Bioinformatics and Ph.D. in Genetics from the University of Hong Kong.


Paul Tang

AccuraGen, San Jose, CA, United States

While different features of cell-free DNA (cfDNA) have been utilized for early cancer detection, somatic mutation has been shown to offer the highest specificity for ctDNA detection. The recent drop of sequencing cost makes it possible to track thousands of somatic variants from the cancer genomes as cancer markers in plasma, achieving high sensitivity for molecular residual disease detection. This approach, however, will be limited by errors introduced during library preparation and sequencing. Here, we describe AccuScan, a highly accurate and efficient whole genome sequencing technology that enables effective genome wide error suppression at single read level. AccuScan combines rolling cycle amplification with concatemer based error correction to remove both polymerase errors and sequencing errors. We deploy this technology in whole genome sequencing of cfDNA and demonstrated >95% sensitivity at 10-5 variant allele frequency with a specificity of 98% in an analytical study using contrived samples. AccuScan provides a high performance and scalable MRD solution that is tumor informed without personalized design.