Comprehensive Detection of Single Amino Acid Variants and Evaluation of Their Deleterious Potential in a PANC-1 Cell Line.
Comprehensive Detection of Single Amino Acid Variants and Evaluation of Their Deleterious Potential in a PANC-1 Cell Line.
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DOI：
10.1021/acs.jproteome.9b00840
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发表时间：
2020-02
影响因子：
4.4
通讯作者：
Zhijing Tan;Jianhui Zhu;P. Stemmer;Liangliang Sun;Zhichang Yang;Kendall Schultz;Matthew J. Gaffrey;Anthony J. Cesnik;Xinpei Yi;Xiaohu Hao;M. Shortreed;Tujin Shi;D. Lubman
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文献类型：
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作者：
Zhijing Tan;Jianhui Zhu;P. Stemmer;Liangliang Sun;Zhichang Yang;Kendall Schultz;Matthew J. Gaffrey;Anthony J. Cesnik;Xinpei Yi;Xiaohu Hao;M. Shortreed;Tujin Shi;D. Lubman
识别癌症中的单氨基酸变异 (SAAV) 对于精准肿瘤学至关重要。现在有几种先进的算法可用于识别 SAAV，但尝试组合不同的算法并在大型数据集上对其进行优化以实现更全面的 SAAV 覆盖范围尚未实现。在此，我们报告了使用三种不同策略对 PANC-1 细胞系中 SAAV 进行的扩展检测，结果在质谱数据中鉴定出了 540 个 SAAV。在这组 540 个 SAAV 中，根据使用新型 AssVar 软件的分析，其中 79 个被评估为有害 SAAV，其中使用独立选择反应监测 (SRM) 分析进一步验证了 KRAS、TP53 和 SLC37A4 每种蛋白中发现的驱动突变之一。我们的研究代表了迄今为止对 SAAV 最全面的发现，也是首次在 PANC-1 细胞系中大规模检测到有害 SAAV。这项工作可以作为胰腺癌和个人免疫治疗的未来研究的基础。
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 datasets 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 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 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.