Strategy for sensitive and specific somatic SNV/InDel calling: Leveraging different callers with in-house generated gold standard variant sets.

e13104Background: Somatic mutation calling is critical for cancer genotyping. Although rapid development of mutation detection is witnessed with the maturity of NGS, the need for high sensitivity often results in compromised specificity and manual inspection. Here, we propose a methodology that leverages different variant callers to account for specificity without compromising sensitivity. Methods: We designed a cohort of training samples (n = 22), each with known set of SNVs/InDels that were discovered by KEW CANCERPLEX platform. We assessed the performance of four prevailing mutation callers that utilize different statistical approaches and therefore have different calls, using the training samples. We optimized the parameters of the four variant callers to detect all expected variants. We then examined the intersections of every combination of the four callers and identified the best one that eliminated the highest rate of false calls. A customized tool was developed for the intersection of component S...