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The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

机译：人黑色素瘤蛋白质组成像蛋白酶蛋白酶体转录组

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The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16?000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13?176 protein‐coding genes, represented by 366?172 peptides, in addition to 52?000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12?751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease.
机译：MM500 Meta-研究旨在建立肿瘤蛋白质组的知识基础，作为基因组和转录组研究的补充。体细胞瘤的体细胞突变及其对转录组的影响已被广泛表征。然而，这些遗传变化对蛋白质组学景观的影响和对黑色素瘤细胞过程的影响仍然明显。在该研究中，基于定量的质谱型蛋白质组学分析与病理肿瘤表征界面，与临床数据相关。通过分析505次注释的黑素瘤肿瘤样品获得的黑色素瘤蛋白质横向，该蛋白质基于近16Ω000蛋白定义，包括驾驶员基因的突变蛋白质ord。分析了5000多万MS / MS光谱，导致约13,600万肽谱匹配（PSM）。共13〜176蛋白编码基因，除了52〜000磷酸化位点之外，也是366〜172肽的基因，并成功地注释了4个400个乙酰化位点。该数据分别占据65％和74％的预测和鉴定的人蛋白质组。在TCGA储存库的黑素瘤转录组中，高度相关性（Pearson，高达0.54），发现了12？751个基因产物的重叠。通过基因组测序单独预测，不得预先预测表达的蛋白质的映射，即表达的蛋白质，即种定量，瞬发，突变，接头同种型和PTM变体。通过分析血液蛋白表达分析，包括蛋白质的分析，包括在免疫疗法后调节的蛋白质数据的补充。通过加入这些关键蛋白质组织，MM500研究扩大了对黑色素瘤疾病的知识。

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