Dr. Yexun ('Bill') Wang, Senior Director R&D, Frederick, MD.
Research is generally a very slow process, but Bill Wang and his team have delivered a tidal wave of results fast in recent years: six patent applications, five papers, three digital sequencing product lines since 2013. For clinical researchers around the world, the most important breakthrough is probably his work on digital sequencing technology, a novel method that can count and differentiate individual DNA molecules during the next-generation sequencing (NGS) workflow.
The brain behind this technology grew up in China and acquired the nickname ’Bill’ in school English lessons. In 1998, he moved to Minneapolis where he earned a PhD at the University of Minnesota. He first worked for SABiosciences, a company acquired by QIAGEN in 2009, and gained a reputation as a courageous, unconventional mind. “I’m an out-of-the-box thinker,” Bill says, “but I’m also a perfectionist. I never take blind risks and do lots of thinking and calculations before I undertake something.”
Bill’s pioneering work began with a critical evaluation of the first NGS panels: “They had certain deficiencies, for example it was impossible to differentiate between artificially induced bias and genuine mutations.” Bill and his team then analyzed academic papers on how molecular barcodes can be used to overcome this problem. “We saw molecular barcodes as a potential game changer,” Bill says. “The challenge for us was to modify our system to fit these academic findings and scale them up for industrial implementation.” After QIAGEN separated research from development in Life Sciences, Bill and his team were able to concentrate all their efforts on their research work – with impressive results.
QIAGEN’s current NGS research panels are significantly more reliable than alternative technologies in detecting DNA mutations in cancer samples. Their sensitivity has been improved to <1 %, which allows detection of even extremely rare genetic variants or tumor fragments in large volume liquid biopsy samples. This improvement was validated by an extensive study Bill’s team conducted using 6,000 reported mutations. Besides this high analytical sensitivity in mutation detection, enhanced digital sequencing also brings the benefits of low noise and improved reproducibility of results. But Bill isn’t satisfied with the improvement to <1 %. He and his team are already pushing the accuracy of mutation detection in cancer samples towards 99.9 %, while also working to simultaneously analyze DNA and RNA via digital sequencing, and applying the molecular barcode in other applications, e.g. single cell analysis. “I like to work on difficult things,” Bill admits. “And most time I get them done.” Not least thanks to faster, out-of-the-box thinking.