Topic for May: Towards best practices in cancer mutation detection with whole-genome and whole-exome sequencing 

This May, the CGC Webinar series features a presentation by Dr. Wenming Xiao, Lead Bioinformatics Scientist of the Office of New Drugs and the Office of Oncological Diseases, at the Center for Drug Evaluation and Research, of the Food and Drug Administration (FDA). First formed in 1906, the United States FDA’s mission is to promote and protect public health by ensuring the safety and efficacy of food products, drugs, vaccines, cosmetics, and medical devices, among many others.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of NGS. To date, no bulk sequencing study has addressed the effects of cross-site reproducibility or the biological, technical, and computational factors that influence variant identification.

In this upcoming webinar, Dr. Xiao will discuss his research into the systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), Dr. Xiao evaluated the reproducibility of different sample types with varying input amount and tumor purity, multiple library construction protocols, followed by processing with nine bioinformatics pipelines. As a result, he found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, GC content, and the Global Imbalance Value (GIV; G>T/C>A) score. Finally, taking into account library preparation protocol, tumor content, read coverage, and bioinformatics processes concomitantly, Dr. Xiao is able to recommend actionable practices to improve reproducibility and accuracy of NGS experiments for cancer mutation detection.

Wenming Xiao, Ph.D.