An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer
An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer
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DOI：
10.1074/mcp.m115.056226
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发表时间：
2016-03-01
影响因子：
7
通讯作者：
Fenyo, David
中科院分区：
文献类型：
--
作者：
Ruggles, Kelly V.;Tang, Zuojian;Fenyo, David
基于质谱 (MS) 的肽测序的改进为确定癌细胞中鉴定的多态性、突变和剪接变体是否被翻译提供了新的机会。在这里，我们应用蛋白质组数据集成工具（QUILTS）来说明蛋白质变异的发现，使用从一对管腔和基底样乳腺癌患者来源的异种移植物（PDX）生成的全基因组、全转录组和全局蛋白质组数据集。使用多个 MS/MS 样品过程重复（此处定义为使用相同样品材料的独立串联 MS 实验）来探测蛋白质基因组分析对单核苷酸变异 (SNV) 表达和新型剪接点 (NSJ) 检测的敏感性。尽管对 30 多个样品过程重复进行了分析，但通过 DNA 和 RNA 测序检测到的 SNV（体细胞和种系）中只有约 10% 被观察为肽。通过 RNA 测序观察到的与 NSJ 相对应的肽的比例甚至更小（
Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (