Integrative Proteogenomics Using ProteomeGenerator2.
Integrative Proteogenomics Using ProteomeGenerator2.
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DOI：
10.1021/acs.jproteome.3c00005
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发表时间：
2023-07
影响因子：
4.4
通讯作者：
Nathaniel Kwok;Zita E H Aretz;Sumiko Takao;Zheng Ser;P. Cifani;A. Kentsis
中科院分区：
文献类型：
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作者：
Nathaniel Kwok;Zita E H Aretz;Sumiko Takao;Zheng Ser;P. Cifani;A. Kentsis
核酸测序的最新进展现在可以对遗传变异和转录进行快速和基因组规模的分析，从而能够对人类生物学、疾病和各种生物进行种群规模的研究。同样，质谱学蛋白质组学的进步现在可以在整个蛋白质组范围内对蛋白质表达进行高度敏感和准确的研究。然而，大多数蛋白质组学研究依赖于共识数据库来匹配光谱与多肽和蛋白质序列，因此仍然局限于对规范蛋白质序列的分析。在这里，我们开发了基于可伸缩和模块化的ProteomeGenerator框架的ProteomeGenerator 2(Pg2)。PG2整合了基因组和转录组测序，以包括包含氨基酸替换、插入和缺失的蛋白质变体，以及由基因组和转录变异引起的非规范阅读框架、外显子和其他变体。我们使用合成数据以及人类白血病细胞的基因组、转录组和蛋白质组分析对pg2进行了基准测试。PG2可以与当前和新兴的测序技术、汇编器、变种调用器和质谱分析算法相集成，并且可以从https://github.com/kentsisresearchgroup/ProteomeGenerator2.获得开源
Recent advances in nucleic acid sequencing now permit rapid and genome-scale analysis of genetic variation and transcription, enabling population-scale studies of human biology, disease, and diverse organisms. Likewise, advances in mass spectrometry proteomics now permit highly sensitive and accurate studies of protein expression at the whole proteome-scale. However, most proteomic studies rely on consensus databases to match spectra to peptide and protein sequences, and thus remain limited to the analysis of canonical protein sequences. Here, we develop ProteomeGenerator2 (PG2), based on the scalable and modular ProteomeGenerator framework. PG2 integrates genome and transcriptome sequencing to incorporate protein variants containing amino acid substitutions, insertions, and deletions, as well as noncanonical reading frames, exons, and other variants caused by genomic and transcriptomic variation. We benchmarked PG2 using synthetic data and genomic, transcriptomic, and proteomic analysis of human leukemia cells. PG2 can be integrated with current and emerging sequencing technologies, assemblers, variant callers, and mass spectral analysis algorithms, and is available open-source from https://github.com/kentsisresearchgroup/ProteomeGenerator2.