Comprehensive Detection of Single Amino Acid Variants and Evaluation of Their Deleterious Potential in a PANC‑1 Cell Line
journal contributionposted on 2020-02-27, 17:43 authored by Zhijing Tan, Jianhui Zhu, Paul M. Stemmer, Liangliang Sun, Zhichang Yang, Kendall Schultz, Matthew J. Gaffrey, Anthony J. Cesnik, Xinpei Yi, Xiaohu Hao, Michael R. Shortreed, Tujin Shi, David M. Lubman
Identifying single amino acid variants (SAAVs) in cancer is critical for precision oncology. Several advanced algorithms are now available to identify SAAVs, but attempts to combine different algorithms and optimize them on large data sets to achieve a more comprehensive coverage of SAAVs have not been implemented. Herein, we report an expanded detection of SAAVs in the PANC-1 cell line using three different strategies, which results in the identification of 540 SAAVs in the mass spectrometry data. Among the set of 540 SAAVs, 79 are evaluated as deleterious SAAVs based on analysis using the novel AssVar software in which one of the driver mutations found in each protein of KRAS, TP53, and SLC37A4 is further validated using independent selected reaction monitoring (SRM) analysis. Our study represents the most comprehensive discovery of SAAVs to date and the first large-scale detection of deleterious SAAVs in the PANC-1 cell line. This work may serve as the basis for future research in pancreatic cancer and personal immunotherapy and treatment.