CrypticProteinDB

Translated non-canonical proteins derived from noncoding regions or alternative open reading frames (ORFs) can contribute to critical and diverse cellular processes. In the context of cancer, they also represent an under-appreciated source of targets for cancer immunotherapy through their tumor-enriched expression or by harboring somatic mutations that produce neoantigens. Here, we introduce the largest integration and proteogenomic analysis of novel peptides to assess the prevalence of non-canonical ORFs (ncORFs) in more than 900 patient proteomes and 26 immunopeptidome datasets across 14 cancer types. The integrative proteogenomic analysis of whole-cell proteomes and immunopeptidomes revealed peptide support for a nonredundant set of 9760 upstream, downstream, and out-of-frame ncORFs in protein coding genes and 12811 in noncoding RNAs. Notably, 6486 ncORFs were derived from differentially expressed genes and 340 were ubiquitously translated across eight or more cancers.由非编码区域或可变开放阅读框（alternative open reading frames，ORFs）翻译得到的非经典蛋白质，可参与关键且多样的细胞生理过程。在癌症研究语境中，这类蛋白质还可通过肿瘤富集表达，或携带可产生新抗原的体细胞突变，成为癌症免疫治疗中未被充分重视的靶点来源。本研究开展了目前规模最大的新型肽段整合与蛋白质基因组学分析，以评估覆盖14种癌症类型的900余例患者蛋白质组及26个免疫肽组数据集中，非经典开放阅读框（non-canonical ORFs，ncORFs）的表达普遍性。对全细胞蛋白质组与免疫肽组的整合蛋白质基因组学分析结果显示，蛋白编码基因中共存在9760个经肽段证据支持的非冗余上游、下游及读码外非经典开放阅读框，非编码RNA中共存在12811个此类阅读框。值得注意的是，其中6486个非经典开放阅读框源自差异表达基因，另有340个在8种及以上癌症类型中普遍翻译。

搜集汇总

背景与挑战

背景概述

CrypticProteinDB是一个专注于癌症中非经典开放阅读框（ncORFs）的数据库，通过整合超过900个患者蛋白质组和26个免疫肽组数据集，对14种癌症类型进行蛋白质组学分析。该分析揭示了9760个ncORFs和12811个非编码RNA相关ncORFs，其中6486个来源于差异表达基因，340个在八种或更多癌症中普遍翻译。