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Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-treated Pancreatic Beta Cells. 综合多PTM蛋白质组学揭示了细胞因子处理的胰腺β细胞中动态的全局、氧化还原、磷酸化和乙酰化调控。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-14 DOI: 10.1016/j.mcpro.2024.100881
Austin Gluth, Xiaolu Li, Marina A Gritsenko, Matthew J Gaffrey, Doo Nam Kim, Priscila M Lalli, Rosalie K Chu, Nicholas J Day, Tyler J Sagendorf, Matthew E Monroe, Song Feng, Tao Liu, Bin Yang, Wei-Jun Qian, Tong Zhang

Studying regulation of protein function at a systems level necessitates an understanding of the interplay among diverse post-translational modifications (PTMs). A variety of proteomics sample processing workflows are currently used to study specific PTMs but rarely characterize multiple types of PTMs from the same sample inputs. Method incompatibilities and laborious sample preparation steps complicate large-scale physiological investigations and can lead to variations in results. The single-pot, solid-phase-enhanced sample preparation (SP3) method for sample cleanup is compatible with different lysis buffers and amenable to automation, making it attractive for high-throughput multi-PTM profiling. Herein, we describe an integrative SP3 workflow for multiplexed quantification of protein abundance, cysteine thiol oxidation, phosphorylation, and acetylation. The broad applicability of this approach is demonstrated using cell and tissue samples, and its utility for studying interacting regulatory networks is highlighted in a time-course experiment of cytokine-treated β-cells. We observed a swift response in global regulation of protein abundances consistent with rapid activation of JAK-STAT and NF-κB signaling pathways. Regulators of these pathways as well as proteins involved in their target processes displayed multi-PTM dynamics indicative of a complex cellular response stages: acute, adaptation, and chronic (prolonged stress). PARP14, a negative regulator of JAK-STAT, had multiple co-localized PTMs that may be involved in intraprotein regulatory crosstalk. Our workflow provides a high-throughput platform that can profile multi-PTMomes from the same sample set, which is valuable in unraveling the functional roles of PTMs and their co-regulation.

要在系统水平上研究蛋白质的功能调控,就必须了解各种翻译后修饰(PTM)之间的相互作用。目前有多种蛋白质组学样本处理工作流程可用于研究特定的 PTM,但很少能从相同的样本输入中鉴定多种类型的 PTM。方法的不兼容性和繁琐的样品制备步骤使大规模生理学研究变得复杂,并可能导致结果的差异。用于样品清理的单锅固相增强样品制备(SP3)方法可与不同的裂解缓冲液兼容,并可实现自动化,因此对高通量多PTM分析很有吸引力。在此,我们介绍了一种综合的 SP3 工作流程,可对蛋白质丰度、半胱氨酸硫醇氧化、磷酸化和乙酰化进行多重定量。我们利用细胞和组织样本证明了这种方法的广泛适用性,并在细胞因子处理过的β细胞的时程实验中强调了这种方法在研究相互作用的调控网络方面的实用性。我们观察到蛋白质丰度的全局调控反应迅速,与 JAK-STAT 和 NF-κB 信号通路的快速激活相一致。这些通路的调控因子以及参与其目标过程的蛋白质显示出多PTM动态,表明了复杂的细胞反应阶段:急性、适应和慢性(长期应激)。JAK-STAT的负调控因子PARP14有多个共定位PTM,可能参与了蛋白内调控串扰。我们的工作流程提供了一个高通量平台,可以从同一样本集中分析多个PTMomes,这对于揭示PTM的功能作用及其协同调控非常有价值。
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引用次数: 0
Gradient-Elution Nanoflow Liquid Chromatography without a Binary Pump: Smoothed Step Gradients Enable Reproducible, Sensitive, and Low-Cost Separations for Single-Cell Proteomics. 无需二进制泵的梯度洗脱纳升液相色谱法:平滑阶梯梯度使单细胞蛋白质组学的分离具有可重复性、灵敏性和低成本性
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-11 DOI: 10.1016/j.mcpro.2024.100880
Kei G I Webber, Siqi Huang, Hsien-Jung L Lin, Tyler L Hunter, Jeremy Tsang, Dasun Jayatunge, Joshua L Andersen, Ryan T Kelly

Mass spectrometry-based proteome profiling of trace analytes including single cells benefits from liquid chromatography separations operated at low flow rates (e.g., <50 nL/min). However, high-pressure binary pumps needed to achieve such flow rates are not commercially available, and instead require splitting of the gradient flow to achieve low-nanoliter-per-minute flow rates. Gradient flow splitting can waste solvent and lead to flow inconsistencies. To address this, we have developed a method for creating gradients by combining plugs of mobile phase of increasing solvent strength together in a column, and then relying on Taylor dispersion to form the desired smooth gradient profile. Additionally, our method dramatically reduces costs, as only a single isocratic high-pressure pump is required. Following development of gradient profiles for both 10- and 20-min active gradients, we measured 200 pg injections of HeLa digest using a timsTOF mass spectrometer. Finally, we investigated differences in protein expression between single cells originating from two different colonies of ATG-knockout HeLa cells. Thousands of proteins were quantified, and a potential mechanism explaining differential immune responses of these two colonies upon exposure to viral DNA treatment was determined.

以质谱为基础的痕量分析物(包括单细胞)蛋白质组图谱分析得益于以低流速运行的液相色谱分离技术(例如......)、
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引用次数: 0
In-depth analysis of miRNA binding sites reveals the complex response of uterine epithelium to miR-26a-5p and miR-125b-5p during early pregnancy. 对 miRNA 结合位点的深入分析揭示了妊娠早期子宫上皮对 miR-26a-5p 和 miR-125b-5p 的复杂反应。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-11 DOI: 10.1016/j.mcpro.2024.100879
Kamil Myszczynski, Joanna Szuszkiewicz, Kamil Krawczynski, Małgorzata Sikora, Marta Romaniewicz, Maria M Guzewska, Piotr Zabielski, Monika M Kaczmarek

Post-transcriptional regulation of gene expression by miRNAs likely makes significant contributions to mRNA abundance at the embryo-maternal interface. In this study, we investigated how miR-26a-5p and miR-125b-5p contribute to molecular changes occurring in the uterine luminal epithelium, which serves as the first site of signal exchange between the mother and developing embryo. To measure de novo protein synthesis after miRNA delivery to primary uterine luminal epithelial cells, we employed pulsed stable isotope labeling by amino acids (pSILAC). We found that both miRNAs alter the proteome of luminal epithelial cells, impacting numerous cellular functions, immune responses, as well as intracellular and second messenger signaling pathways. Additionally, we identified several features of miRNA-mRNA interactions that may influence the targeting efficiency of miR-26a-5p and miR-125b-5p. Overall, our study suggests a complex interaction of miR-26a-5p and miR-125b-5p with their respective targets. However, both appear to cooperatively function in modulating the cellular environment of the luminal epithelium, facilitating the morphological and molecular changes that occur during the intensive communication between the embryo and uterus at pregnancy.

miRNA 对基因表达的转录后调控可能对胚胎-母体界面的 mRNA 丰度有重大贡献。在这项研究中,我们研究了 miR-26a-5p 和 miR-125b-5p 如何促进子宫腔上皮发生的分子变化,子宫腔上皮是母体和发育中胚胎之间信号交流的第一站。为了测量将 miRNA 运送到原代子宫腔上皮细胞后从头合成蛋白质的情况,我们采用了脉冲式氨基酸稳定同位素标记(pSILAC)技术。我们发现,两种 miRNA 都会改变管腔上皮细胞的蛋白质组,影响多种细胞功能、免疫反应以及细胞内和第二信使信号通路。此外,我们还发现了可能影响 miR-26a-5p 和 miR-125b-5p 靶向效率的 miRNA-mRNA 相互作用的几个特征。总之,我们的研究表明,miR-26a-5p 和 miR-125b-5p 与各自的靶标之间存在着复杂的相互作用。然而,两者似乎在调节管腔上皮细胞环境方面发挥着合作作用,促进了胚胎和子宫在妊娠期密集交流过程中发生的形态和分子变化。
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引用次数: 0
Knockdown proteomics reveals USP7 as a regulator of cell-cell adhesion in colorectal cancer via AJUBA. 基因敲除蛋白质组学揭示 USP7 是通过 AJUBA 调节结直肠癌细胞-细胞粘附的调控因子。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-08 DOI: 10.1016/j.mcpro.2024.100878
Ahood Al-Eidan, Ben Draper, Siyuan Wang, Brandon Coke, Paul Skipp, Yihua Wang, Rob M Ewing

Ubiquitin-specific protease 7 (USP7) is implicated in many cancers including colorectal cancer in which it regulates cellular pathways such as Wnt signalling and the P53-MDM2 pathway. With the discovery of small-molecule inhibitors, USP7 has also become a promising target for cancer therapy, and therefore systematically identifying USP7 deubiquitinase interaction partners and substrates has become an important goal. In this study, we selected a colorectal cancer cell model that is highly dependent on USP7 and in which USP7 knockdown significantly inhibited colorectal cancer cell viability, colony formation, and cell-cell adhesion. We then used inducible knockdown of USP7 followed by LC-MS/MS to quantify USP7 dependent proteins. We identified the Ajuba LIM domain protein as an interacting partner of USP7 through co-IP, its substantially reduced protein levels in response to USP7 knockdown, and its sensitivity to the specific USP7 inhibitor FT671. The Ajuba protein has been shown to have oncogenic functions in colorectal and other tumours, including regulation of cell-cell adhesion. We show that both knockdown of USP7 or Ajuba results in a substantial reduction of cell-cell adhesion, with concomitant effects on other proteins associated with adherens junctions. Our findings underlie the role of USP7 in colorectal cancer through its protein interaction networks and show that the Ajuba protein is a component of USP7 protein networks present in colorectal cancer.

泛素特异性蛋白酶 7(USP7)与包括结直肠癌在内的许多癌症都有关系,它调节着 Wnt 信号和 P53-MDM2 通路等细胞通路。随着小分子抑制剂的发现,USP7 也已成为癌症治疗的一个有希望的靶点,因此系统鉴定 USP7 去泛素化酶相互作用伙伴和底物已成为一个重要目标。在本研究中,我们选择了一种高度依赖 USP7 的结直肠癌细胞模型,在该模型中,敲除 USP7 能显著抑制结直肠癌细胞的活力、集落形成和细胞间粘附。然后,我们利用诱导性敲除 USP7,再通过 LC-MS/MS 对 USP7 依赖性蛋白进行定量。我们通过共质泳(co-IP)发现了Ajuba LIM结构域蛋白是USP7的相互作用伙伴,它的蛋白水平在USP7基因敲除后大幅降低,而且对特异性USP7抑制剂FT671很敏感。Ajuba 蛋白已被证明在结直肠癌和其他肿瘤中具有致癌功能,包括调节细胞-细胞粘附。我们的研究表明,敲除 USP7 或 Ajuba 都会导致细胞-细胞粘附性大幅降低,并同时影响与粘附连接相关的其他蛋白质。我们的研究结果揭示了 USP7 通过其蛋白质相互作用网络在结直肠癌中的作用,并表明 Ajuba 蛋白是结直肠癌中 USP7 蛋白网络的一个组成部分。
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引用次数: 0
Bridging the Gap from Proteomics Technology to Clinical Application: Highlights from the 68th Benzon Foundation Symposium. 缩小蛋白质组学技术与临床应用之间的差距:第 68 届 Benzon 基金会研讨会花絮。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-08 DOI: 10.1016/j.mcpro.2024.100877
Vincent Albrecht, Johannes Müller-Reif, Thierry M Nordmann, Andreas Mund, Lisa Schweizer, Philipp E Geyer, Lili Niu, Juanjuan Wang, Frederik Post, Marc Oeller, Andreas Metousis, Annelaura Bach Nielsen, Medini Steger, Nicolai J Wewer Albrechtsen, Matthias Mann

The 68th Benzon Foundation Symposium brought together leading experts to explore the integration of mass spectrometry (MS)-based proteomics and artificial intelligence in revolutionizing personalized medicine. This report highlights key discussions on recent technological advances in MS-based proteomics, including improvements in sensitivity, throughput, and data analysis. Particular emphasis was placed on plasma proteomics and its potential for biomarker discovery across various diseases. The symposium addressed critical challenges in translating proteomic discoveries to clinical practice, including standardization, regulatory considerations and the need for robust 'business cases' to motivate adoption. Promising applications were presented in areas such as cancer diagnostics, neurodegenerative diseases, and cardiovascular health. The integration of proteomics with other omics technologies and imaging methods was explored, showcasing the power of multi-modal approaches in understanding complex biological systems. Artificial intelligence emerged as a crucial tool for the acquisition of large-scale proteomic datasets, extracting meaningful insights, and enhancing clinical decision-making. By fostering dialogue between academic researchers, industry leaders in proteomics technology, and clinicians, the symposium illuminated potential pathways for proteomics to transform personalized medicine, advancing the cause of more precise diagnostics and targeted therapies.

第 68 届 Benzon 基金会研讨会汇聚了顶尖专家,共同探讨基于质谱(MS)的蛋白质组学与人工智能在革新个性化医疗方面的结合。本报告重点讨论了基于质谱的蛋白质组学的最新技术进展,包括灵敏度、通量和数据分析方面的改进。会议特别强调了血浆蛋白质组学及其在发现各种疾病的生物标记物方面的潜力。研讨会探讨了将蛋白质组学发现转化为临床实践所面临的关键挑战,包括标准化、监管方面的考虑,以及需要强有力的 "商业案例 "来推动应用。会上介绍了在癌症诊断、神经退行性疾病和心血管健康等领域前景广阔的应用。会议探讨了蛋白质组学与其他全息技术和成像方法的整合,展示了多模式方法在理解复杂生物系统方面的力量。人工智能成为获取大规模蛋白质组数据集、提取有意义的见解和加强临床决策的重要工具。通过促进学术研究人员、蛋白质组学技术行业领导者和临床医生之间的对话,研讨会阐明了蛋白质组学改变个性化医疗的潜在途径,推动了更精确的诊断和靶向治疗事业的发展。
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引用次数: 0
Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression. 自上而下的蛋白质组学识别肝硬化进展的血浆蛋白质形式特征
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-07 DOI: 10.1016/j.mcpro.2024.100876
Eleonora Forte, Jes M Sanders, Indira Pla, Vijaya Lakshmi Kanchustambham, Michael A R Hollas, Che-Fan Huang, Aniel Sanchez, Katrina N Peterson, Rafael D Melani, Alexander Huang, Praneet Polineni, Julianna M Doll, Zachary Dietch, Neil L Kelleher, Daniela P Ladner

Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.

肝硬化是一种晚期肝病,影响着 200-500 万美国人。虽然大多数患者为代偿性肝硬化,可能没有明显症状,但许多患者会出现失代偿,出现危及生命的并发症,如消化道出血、意识模糊(肝性脑病)和腹水,使预期寿命从 12 年缩短到不足 2 年。在代偿期肝硬化患者中,识别失代偿高风险患者对于优化护理、降低发病率和死亡率至关重要。因此,必须优先引导他们接受专科治疗,而专科治疗不可能提供给所有肝硬化患者。我们利用自上而下蛋白质组学(TDP)发现肝硬化进展期患者血浆中的差异表达蛋白形式(DEPs),最终目标是确定疾病进展的候选生物标志物。在这项试验性研究中,我们在肝硬化的三个阶段(代偿期、门脉高压代偿期和失代偿期)中鉴定出了 209 个 DEPs,其中 115 个来自肝脏中转录水平富集的蛋白质,并能区分肝硬化的三个阶段。富集分析表明,DEPs 参与了多个已知受肝硬化进展影响的代谢和免疫过程。我们已经初步确定了肝硬化患者的血浆蛋白形式特征,为正在进行的早期诊断、风险分层和疾病监测生物标记物的发现和验证奠定了基础。
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引用次数: 0
The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry. Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-06 DOI: 10.1016/j.mcpro.2024.100875
Lissa C Anderson, Dina L Bai, Greg T Blakney, David S Butcher, Larry Reser, Jeffrey Shabanowitz

Donald Hunt has made seminal contributions to the fields of proteomics, immunology, epigenetics, and glycobiology. The foundation of every important work to come out of the Hunt Laboratory is de novo peptide sequencing. For decades, he taught hundreds of students, postdocs, engineers, and scientists to directly interpret mass spectral data. To honor his legacy and ensure that the art of de novo sequencing is not lost, we have adapted his teaching materials into "The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry". In addition to the de novo sequencing tutorials, we present two freely available software tools that facilitate manual interpretation of mass spectra and validation of search results. The first, "Hunt Lab Peptide Fragment Calculator", calculates precursor and fragment mass-to-charge ratios for any peptide. The second program, "Predator Protein Fragment Calculator", was inspired in part by the fragment calculator developed in the Hunt Lab. Its capabilities are enhanced to facilitate interpretation of mass spectral data derived from intact proteins. We hope that the combination of these educational tools will continue to benefit students and researchers by empowering them to interpret data on their own.

唐纳德-亨特在蛋白质组学、免疫学、表观遗传学和糖生物学领域做出了开创性的贡献。亨特实验室每一项重要工作的基础都是全新肽测序。几十年来,他教会了数百名学生、博士后、工程师和科学家直接解读质谱数据。为了缅怀他的丰功伟绩,并确保从头测序技术不会失传,我们将他的教学材料改编成《Hunt 实验室串联质谱从头肽段分析指南》。除了从头测序教程,我们还介绍了两款免费提供的软件工具,方便用户手动解读质谱和验证搜索结果。第一个软件是 "Hunt Lab 多肽片段计算器",可以计算任何多肽的前体和片段质量电荷比。第二个程序 "Predator 蛋白片段计算器 "的部分灵感来自 Hunt 实验室开发的片段计算器。该程序的功能得到了增强,便于解读来自完整蛋白质的质谱数据。我们希望将这些教育工具结合起来,使学生和研究人员有能力自己解读数据,从而继续从中受益。
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引用次数: 0
Identification of Proteome-Based Immune Subtypes of Early Hepatocellular Carcinoma and Analysis of Potential Metabolic Drivers. 早期肝细胞癌蛋白质组免疫亚型鉴定及潜在代谢驱动因素分析
IF 7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-11-25 DOI: 10.1016/j.mcpro.2023.100686
Lihong Diao, Mengqi He, Binsheng Xu, Lanhui Chen, Ze Wang, Yuting Yang, Simin Xia, Shengwei Hu, Shuzhen Guo, Dong Li

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, ranking fourth in frequency. The relationship between metabolic reprogramming and immune infiltration has been identified as having a crucial impact on HCC progression. However, a deeper understanding of the interplay between the immune system and metabolism in the HCC microenvironment is required. In this study, we used a proteomic dataset to identify three immune subtypes (IM1-IM3) in HCC, each of which has distinctive clinical, immune, and metabolic characteristics. Among these subtypes, IM3 was found to have the poorest prognosis, with the highest levels of immune infiltration and T-cell exhaustion. Furthermore, IM3 showed elevated glycolysis and reduced bile acid metabolism, which was strongly correlated with CD8 T cell exhaustion and regulatory T cell accumulation. Our study presents the proteomic immune stratification of HCC, revealing the possible link between immune cells and reprogramming of HCC glycolysis and bile acid metabolism, which may be a viable therapeutic strategy to improve HCC immunotherapy.

肝细胞癌(HCC)是全球癌症相关死亡的主要原因,发病率排名第四。代谢重编程和免疫浸润之间的关系已被确定为对HCC进展具有重要影响。然而,需要对肝细胞癌微环境中免疫系统和代谢之间的相互作用有更深入的了解。在这项研究中,我们使用蛋白质组学数据集来鉴定HCC中的三种免疫亚型(IM1-IM3),每种亚型都具有独特的临床、免疫和代谢特征。在这些亚型中,IM3预后最差,免疫浸润和t细胞衰竭水平最高。此外,IM3表现出糖酵解升高和胆汁酸代谢降低,这与CD8 T细胞耗竭和调节性T细胞积累密切相关。我们的研究提出了HCC的蛋白质组免疫分层,揭示了免疫细胞与HCC糖酵解和胆汁酸代谢重编程之间的可能联系,这可能是改善HCC免疫治疗的可行治疗策略。
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引用次数: 0
Detection of Pancreatic Ductal Adenocarcinoma-Associated Proteins in Serum. 血清胰腺导管腺癌相关蛋白的检测。
IF 7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-11-27 DOI: 10.1016/j.mcpro.2023.100687
T Mamie Lih, Liwei Cao, Parham Minoo, Gilbert S Omenn, Ralph H Hruban, Daniel W Chan, Oliver F Bathe, Hui Zhang

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, partly because it is frequently identified at an advanced stage, when surgery is no longer feasible. Therefore, early detection using minimally invasive methods such as blood tests may improve outcomes. However, studies to discover molecular signatures for the early detection of PDAC using blood tests have only been marginally successful. In the current study, a quantitative glycoproteomic approach via data-independent acquisition mass spectrometry was utilized to detect glycoproteins in 29 patient-matched PDAC tissues and sera. A total of 892 N-linked glycopeptides originating from 141 glycoproteins had PDAC-associated changes beyond normal variation. We further evaluated the specificity of these serum-detectable glycoproteins by comparing their abundance in 53 independent PDAC patient sera and 65 cancer-free controls. The PDAC tissue-associated glycoproteins we have identified represent an inventory of serum-detectable PDAC-associated glycoproteins as candidate biomarkers that can be potentially used for the detection of PDAC using blood tests.

胰腺导管腺癌(PDAC)是最致命的癌症类型之一,部分原因是它经常在晚期被发现,此时手术不再可行。因此,使用血液检查等微创方法进行早期检测可能会改善预后。然而,利用血液检测发现PDAC早期检测的分子特征的研究只取得了些微的成功。在目前的研究中,通过数据独立获取质谱(DIA-MS)的定量糖蛋白组学方法被用于检测29例患者匹配的PDAC组织和血清中的糖蛋白。来自141种糖蛋白的892种n链糖肽发生了超出正常变异的PDAC相关变化。通过比较53例独立PDAC患者血清和65例无癌对照血清中这些血清可检测糖蛋白的丰度,我们进一步评估了它们的特异性。我们已经确定的PDAC组织相关糖蛋白代表了血清可检测的PDAC相关糖蛋白的清单,作为候选生物标志物,可以潜在地用于通过血液测试检测PDAC。
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引用次数: 0
iProPhos: A Web-Based Interactive Platform for Integrated Proteome and Phosphoproteome Analysis. iProPhos:基于网络的综合蛋白质组和磷酸蛋白质组分析互动平台。
IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-12-12 DOI: 10.1016/j.mcpro.2023.100693
Jing Zou, Ziran Qin, Ran Li, Xiaohua Yan, Huizhe Huang, Bing Yang, Fangfang Zhou, Long Zhang

Large-scale omics studies have generated a wealth of mass spectrometry-based proteomics data, which provide additional insights into disease biology spanning genomic boundaries. However, there is a notable lack of web-based analysis and visualization tools that facilitate the reutilization of these data. Given this challenge, we present iProPhos, a user-friendly web server to deliver interactive and customizable functionalities. iProPhos incorporates a large number of samples, including 1444 tumor samples and 746 normal samples across 12 cancer types, sourced from the Clinical Proteomic Tumor Analysis Consortium. Additionally, users can also upload their own proteomics/phosphoproteomics data for analysis and visualization. In iProPhos, users can perform profiling plotting and differential expression, patient survival, clinical feature-related, and correlation analyses, including protein-protein, mRNA-protein, and kinase-substrate correlations. Furthermore, functional enrichment, protein-protein interaction network, and kinase-substrate enrichment analyses are accessible. iProPhos displays the analytical results in interactive figures and tables with various selectable parameters. It is freely accessible at http://longlab-zju.cn/iProPhos without login requirement. We present two case studies to demonstrate that iProPhos can identify potential drug targets and upstream kinases contributing to site-specific phosphorylation. Ultimately, iProPhos allows end-users to leverage the value of big data in cancer proteomics more effectively and accelerates the discovery of novel therapeutic targets.

大规模的组学研究产生了大量基于质谱的蛋白质组学数据,这些数据提供了对跨越基因组边界的疾病生物学的更多见解。然而,基于网络的分析和可视化工具明显不足,无法促进这些数据的再利用。iProPhos整合了大量样本,包括来自临床肿瘤蛋白质组分析联盟的12种癌症类型的1444个肿瘤样本和746个正常样本。此外,用户还可以上传自己的蛋白质组学/磷蛋白组学数据进行分析和可视化。在 iProPhos 中,用户可以进行剖析图绘制和差异表达、患者生存、临床特征相关和相关性分析,包括蛋白质-蛋白质、mRNA-蛋白质和激酶-底物相关性分析。此外,还可进行功能富集、蛋白-蛋白相互作用网络和激酶-底物富集分析。iProPhos 通过交互式图表和表格显示分析结果,并提供各种可选参数。它可在 http://longlab-zju.cn/iProPhos 免费访问,无需登录。我们介绍了两个案例研究,以证明 iProPhos 可以识别潜在的药物靶点和导致位点特异性磷酸化的上游激酶。最终,iProPhos 使最终用户能够更有效地利用癌症蛋白质组学大数据的价值,并加速发现新的治疗靶点。
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引用次数: 0
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Molecular & Cellular Proteomics
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