Journal of Proteome Research最新文献

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MSIght: A Modular Platform for Improved Confidence in Global, Untargeted Mass Spectrometry Imaging Annotation. MSIght:一个模块化平台,用于提高全球非靶向质谱成像注释的信心。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-04-08 DOI: 10.1021/acs.jproteome.4c01140
Lauren Fields, Hannah N Miles, Alexis E Adrian, Elliot Patrenets, William A Ricke, Lingjun Li
{"title":"MSIght: A Modular Platform for Improved Confidence in Global, Untargeted Mass Spectrometry Imaging Annotation.","authors":"Lauren Fields, Hannah N Miles, Alexis E Adrian, Elliot Patrenets, William A Ricke, Lingjun Li","doi":"10.1021/acs.jproteome.4c01140","DOIUrl":"10.1021/acs.jproteome.4c01140","url":null,"abstract":"<p><p>Mass spectrometry imaging (MSI) has gained popularity in clinical analyses due to its high sensitivity, specificity, and throughput. However, global profiling experiments are often still restricted to LC-MS/MS analyses that lack spatial localization due to low-throughput methods for on-tissue peptide identification and confirmation. Additionally, the integration of parallel LC-MS/MS peptide confirmation, as well as histological stains for accurate mapping of identifications, presents a large bottleneck for data analysis, limiting throughput for untargeted profiling experiments. Here, we present a novel platform, termed MSIght, which automates the integration of these multiple modalities into an accessible and modular platform. Histological stains of tissue sections are coregistered to their respective MSI data sets to improve spatial localization and resolution of identified peptides. MS/MS peptide identifications via untargeted LC-MS/MS are used to confirm putative MSI identifications, thus generating MS images with greater confidence in a high-throughput, global manner. This platform has the potential to enable large-scale clinical cohorts to utilize MSI in the future for global proteomic profiling that uncovers novel biomarkers in a spatially resolved manner, thus widely expanding the utility of MSI in clinical discovery.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2478-2490"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Open-Source and FAIR Research Software for Proteomics. 蛋白质组学的开源和公平研究软件。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-04-23 DOI: 10.1021/acs.jproteome.4c01079
Yasset Perez-Riverol, Wout Bittremieux, William S Noble, Lennart Martens, Aivett Bilbao, Michael R Lazear, Bjorn Grüning, Daniel S Katz, Michael J MacCoss, Chengxin Dai, Jimmy K Eng, Robbin Bouwmeester, Michael R Shortreed, Enrique Audain, Timo Sachsenberg, Jeroen Van Goey, Georg Wallmann, Bo Wen, Lukas Käll, William E Fondrie
{"title":"Open-Source and FAIR Research Software for Proteomics.","authors":"Yasset Perez-Riverol, Wout Bittremieux, William S Noble, Lennart Martens, Aivett Bilbao, Michael R Lazear, Bjorn Grüning, Daniel S Katz, Michael J MacCoss, Chengxin Dai, Jimmy K Eng, Robbin Bouwmeester, Michael R Shortreed, Enrique Audain, Timo Sachsenberg, Jeroen Van Goey, Georg Wallmann, Bo Wen, Lukas Käll, William E Fondrie","doi":"10.1021/acs.jproteome.4c01079","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01079","url":null,"abstract":"<p><p>Scientific discovery relies on innovative software as much as experimental methods, especially in proteomics, where computational tools are essential for mass spectrometer setup, data analysis, and interpretation. Since the introduction of SEQUEST, proteomics software has grown into a complex ecosystem of algorithms, predictive models, and workflows, but the field faces challenges, including the increasing complexity of mass spectrometry data, limited reproducibility due to proprietary software, and difficulties integrating with other omics disciplines. Closed-source, platform-specific tools exacerbate these issues by restricting innovation, creating inefficiencies, and imposing hidden costs on the community. Open-source software (OSS), aligned with the FAIR Principles (Findable, Accessible, Interoperable, Reusable), offers a solution by promoting transparency, reproducibility, and community-driven development, which fosters collaboration and continuous improvement. In this manuscript, we explore the role of OSS in computational proteomics, its alignment with FAIR principles, and its potential to address challenges related to licensing, distribution, and standardization. Drawing on lessons from other omics fields, we present a vision for a future where OSS and FAIR principles underpin a transparent, accessible, and innovative proteomics community.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"24 5","pages":"2222-2234"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of High-Fat Diet-induced Metabolic Dysfunction-associated Steatotic Liver Disease on Heart, Kidney, and Skeletal Muscle Metabolomes in Wild-Type Mice. 高脂肪饮食诱导的代谢功能障碍相关脂肪变性肝病对野生型小鼠心脏、肾脏和骨骼肌代谢组的影响
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-04-13 DOI: 10.1021/acs.jproteome.5c00040
João G Silva, Ludgero Tavares, Getachew D Belew, João A Rodrigues, Rita Araújo, Ana M Gil, John G Jones
{"title":"Impact of High-Fat Diet-induced Metabolic Dysfunction-associated Steatotic Liver Disease on Heart, Kidney, and Skeletal Muscle Metabolomes in Wild-Type Mice.","authors":"João G Silva, Ludgero Tavares, Getachew D Belew, João A Rodrigues, Rita Araújo, Ana M Gil, John G Jones","doi":"10.1021/acs.jproteome.5c00040","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00040","url":null,"abstract":"<p><p><b>Background:</b> Metabolic dysfunction-associated steatotic liver disease (MASLD) can be recapitulated in mice fed a high-fat diet. The development of MASLD and the diet <i>per se</i> can both perturb metabolism in key extrahepatic tissues such as the heart, kidney, and skeletal muscle. To date, these alterations have not been well described in this animal model of diet-induced MASLD. <b>Methodology:</b> Male C57BL/6J mice were fed either standard (SC, <i>n</i> = 12) or high-fat chow (HF, <i>n</i> = 11) for 18 weeks. Metabolites were extracted from the heart, kidney, and skeletal muscle and analyzed by <sup>1</sup>H nuclear magnetic resonance (NMR) spectroscopy, along with multivariate and univariate statistical analyses. <b>Results:</b> Kidney metabolite profiles exhibited the largest differences between HF and SC diets, followed by those of skeletal muscle and then the heart. Some alterations were common across all tissues, namely decreased trimethylamine and elevated levels of linoleic acid and polyunsaturated fatty acids in HF compared to SC (<i>p</i> < 0.05 for all three metabolites). Overall, the metabolite variations were consistent with shifts in carbohydrate and lipid substrate selection for oxidation, increased tissue stress in the heart and kidneys, and altered choline metabolism. These findings may serve as additional important descriptors of MASLD onset and progression.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"24 5","pages":"2491-2504"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep Learning-Based Prediction of Decoy Spectra for False Discovery Rate Estimation in Spectral Library Searching. 基于深度学习的光谱库搜索中错误发现率估计的诱饵光谱预测。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-04-19 DOI: 10.1021/acs.jproteome.4c00304
Chak Ming Jerry Chan, Dominik Madej, Chun Kit Jason Chung, Henry Lam
{"title":"Deep Learning-Based Prediction of Decoy Spectra for False Discovery Rate Estimation in Spectral Library Searching.","authors":"Chak Ming Jerry Chan, Dominik Madej, Chun Kit Jason Chung, Henry Lam","doi":"10.1021/acs.jproteome.4c00304","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00304","url":null,"abstract":"<p><p>With the advantage of extensive coverage, predicted spectral libraries are becoming an attractive alternative in proteomic data analysis. As a popular false discovery rate estimation method, target decoy search has been adopted in library search workflows. While existing decoy methods for curated experimental libraries have been tested, their performance in predicted library scenarios remains unknown. Current methods rely on perturbing real spectra templates, limiting the diversity and number of decoy spectra that can be generated for a given library. In this study, we explore the shuffle-and-predict decoy library generation approach, which can generate decoy spectra without the need for template spectra. Our experiments shed light on decoy method performance for predicted library scenarios and demonstrate the quality of predicted decoys in FDR estimation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"24 5","pages":"2235-2242"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CE-MS Metabolomic and LC-MS Proteomic Analyses of Breast Cancer Exosomes Reveal Alterations in Purine and Carnitine Metabolism. 乳腺癌外泌体的CE-MS代谢组学和LC-MS蛋白质组学分析揭示了嘌呤和肉毒碱代谢的改变。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-03-04 DOI: 10.1021/acs.jproteome.4c00795
Emil A Zaripov, Abdullah Khraibah, Petr Kasyanchyk, Aliaksandra Radchanka, Nico Hüttmann, Maxim V Berezovski
{"title":"CE-MS Metabolomic and LC-MS Proteomic Analyses of Breast Cancer Exosomes Reveal Alterations in Purine and Carnitine Metabolism.","authors":"Emil A Zaripov, Abdullah Khraibah, Petr Kasyanchyk, Aliaksandra Radchanka, Nico Hüttmann, Maxim V Berezovski","doi":"10.1021/acs.jproteome.4c00795","DOIUrl":"10.1021/acs.jproteome.4c00795","url":null,"abstract":"<p><p>A nanosheath-flow capillary electrophoresis mass spectrometry (CE-MS) system with electrospray ionization was used to profile cationic metabolite cargo in exosomes secreted by nontumorigenic MCF-10A and tumorigenic MDA-MB-231 breast epithelial cells. An in-house-produced sheath liquid interface was developed and machined from PEEK to enable nanoflow volumes. Normalization of CE-MS peak areas to the total UV signal was employed to enhance quantitative accuracy and reduce variability. CE-MS-based metabolomics revealed increased purine synthesis intermediates and increased carnitine synthesis metabolites in MDA-MB-231-derived exosomes, with pathway enrichment indicating the activation of de novo purine pathways and upregulation of carnitine metabolism. In addition, nano-LC-MS-based proteomics revealed differential expression of ecto-5'-nucleotidase (NT5E) and mitochondrial aldehyde dehydrogenase (ALDH9A1), demonstrating metabolic alterations in related enzymatic steps. This study demonstrates the application of nanosheath-flow CE-MS for comprehensive and quantitative exosome metabolomics, uncovering metabolic reprogramming in purine and carnitine pathways between normal and cancerous breast cell lines and providing insight into exosome-mediated signaling of breast cancer metabolism.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2505-2516"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glycoproteomics Analysis of Triple Wild-Type Lung Adenocarcinoma Tissue Samples. 三种野生型肺腺癌组织样本的糖蛋白组学分析。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-02 Epub Date: 2025-04-02 DOI: 10.1021/acs.jproteome.4c01063
Simon Nándor Sugár, Balázs András Molnár, Fanni Bugyi, Gábor Kecskeméti, Zoltán Szabó, Ibolya Laczó, Tünde Harkó, Judit Moldvay, Lilla Turiák
{"title":"Glycoproteomics Analysis of Triple Wild-Type Lung Adenocarcinoma Tissue Samples.","authors":"Simon Nándor Sugár, Balázs András Molnár, Fanni Bugyi, Gábor Kecskeméti, Zoltán Szabó, Ibolya Laczó, Tünde Harkó, Judit Moldvay, Lilla Turiák","doi":"10.1021/acs.jproteome.4c01063","DOIUrl":"10.1021/acs.jproteome.4c01063","url":null,"abstract":"<p><p>Lung cancer has both high incidence and mortality, making it the leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease, with several histological subtypes and genetic alterations that influence prognosis and available treatment options. Here, we focus on the triple wild-type (TWT) subtype of lung adenocarcinoma (LUAD) that lacks the three most common actionable genetic alterations, subsequently making targeted therapies inaccessible. In this study, our aim was the mass spectrometry-based proteomic and <i>N</i>-glycoproteomic characterization of tumor and adjacent normal lung tissue regions from individuals (<i>n</i> = 12) with TWT LUAD. We found several proteins previously identified as potential prognostic or diagnostic biomarkers in LUAD and described dysregulated biological processes, giving an overview of the general differences between healthy and tumor tissue. Also, we highlight specific signatures detected using <i>N</i>-glycoproteomics and discuss their potential and importance based on data from databases and literature. To the best of our knowledge, this is the first <i>N</i>-glycoproteomics-focused study on TWT LUAD, and it could provide a valuable resource for further studies into this less well characterized subtype of lung cancer. For instance, we report altered <i>N</i>-glycosylation for several glycoproteins implicated in LUAD and other cancers that could have functional importance connected to the disease.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2419-2429"},"PeriodicalIF":3.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines. 缺氧诱导胰腺腺癌(PDAC)细胞系细胞表面广泛的蛋白和蛋白水解性重塑。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-05-01 DOI: 10.1021/acs.jproteome.4c01037
Irene Lui, Kaitlin Schaefer, Lisa L Kirkemo, Jie Zhou, Rushika M Perera, Kevin K Leung, James A Wells
{"title":"Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines.","authors":"Irene Lui, Kaitlin Schaefer, Lisa L Kirkemo, Jie Zhou, Rushika M Perera, Kevin K Leung, James A Wells","doi":"10.1021/acs.jproteome.4c01037","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01037","url":null,"abstract":"<p><p>The tumor microenvironment (TME) plays a crucial role in cancer progression. Hypoxia is a hallmark of the TME and induces a cascade of molecular events that affect cellular processes involved in metabolism, metastasis, and proteolysis. In pancreatic ductal adenocarcinoma (PDAC), tumor tissues are extremely hypoxic. Here, we leveraged mass spectrometry technologies to examine hypoxia-induced alterations in the abundance and proteolytic modifications to cell surface and secreted proteins. Across four PDAC cell lines, we discovered extensive proteolytic remodeling of cell surface proteins involved in cellular adhesion and motility. Looking outward at the surrounding secreted space, we identified hypoxia-regulated secreted and proteolytically shed proteins involved in regulating the humoral immune and inflammatory response, and an upregulation of proteins involved in metabolic processing and tissue development. Combining cell surface N-terminomics and secretomics to evaluate the cellular response to hypoxia enabled us to identify significantly altered candidate proteins which may serve as potential biomarkers and therapeutic targets in PDAC. Furthermore, this approach provides a blueprint for studying dysregulated extracellular proteolysis in other cancers and inflammatory diseases.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Survival of the Littlest: Navigating Sepsis Diagnosis beyond Inflammation in Preterm Neonates. 最小的生存:导航败血症诊断超越炎症在早产儿。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-04-30 DOI: 10.1021/acs.jproteome.4c01072
Manchu Umarani Thangavelu, Alida Kindt, Shawen Hassan, Jelte J B Geerlings, Charlotte Nijgh-van Kooij, Irwin K M Reiss, Bert Wouters, H Rob Taal, Thomas Hankemeier
{"title":"Survival of the Littlest: Navigating Sepsis Diagnosis beyond Inflammation in Preterm Neonates.","authors":"Manchu Umarani Thangavelu, Alida Kindt, Shawen Hassan, Jelte J B Geerlings, Charlotte Nijgh-van Kooij, Irwin K M Reiss, Bert Wouters, H Rob Taal, Thomas Hankemeier","doi":"10.1021/acs.jproteome.4c01072","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01072","url":null,"abstract":"<p><p>Sepsis diagnosis in preterm neonates is challenging due to symptom overlap with non-infectious inflammatory conditions, and slow, unreliable diagnostic practices. This case-control study aims to elucidate sepsis pathophysiology, and identify metabolic biomarkers for timely, accurate diagnosis, to prevent rapid health deterioration and unnecessary antibiotic use. Liquid chromatography-mass spectrometry was performed on 227 plasma samples, obtained from 94 preterm neonates, to measure 317 metabolites encompassing amines and signaling lipids. Linear mixed-effect modeling, LASSO and logistic regression models were calculated to assess metabolic alterations across control, systemic inflammation-no sepsis (SINS), and sepsis groups. Stratification by sex and pathogen type allowed identification of sex-specific responses and pathogen-driven variations in sepsis. Key findings include (i) shared metabolic changes in SINS and sepsis, (ii) progressive alterations from control to SINS to sepsis, and (iii) sepsis-specific markers. Males exhibited a pro-inflammatory phenotype while females showed an anti-inflammatory phenotype in response to sepsis. Gram-positive and gram-negative bacterial sepsis revealed distinct metabolic profiles. A diagnostic model comprising 5 metabolic features and IL-6 distinguished SINS from sepsis at clinical suspicion (AUC 0.79, sensitivity 0.85, specificity 0.82). These insights highlight the potential of metabolomics to revolutionize neonatal sepsis management with precision diagnostics and personalized treatment strategies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic Proteome Changes in Cuprizone-Induced Demyelination and Remyelination in the Mouse Brain. 铜酮诱导小鼠大脑脱髓鞘和再髓鞘的动态蛋白质组变化。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-04-30 DOI: 10.1021/acs.jproteome.4c01036
Rong-Fang Gu, Xiaoping Hronowski, Zhaohui Shao, Benbo Gao, Kayla Soucey, Fangxu Sun, Hui-Hsin Tsai, Ru Wei
{"title":"Dynamic Proteome Changes in Cuprizone-Induced Demyelination and Remyelination in the Mouse Brain.","authors":"Rong-Fang Gu, Xiaoping Hronowski, Zhaohui Shao, Benbo Gao, Kayla Soucey, Fangxu Sun, Hui-Hsin Tsai, Ru Wei","doi":"10.1021/acs.jproteome.4c01036","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01036","url":null,"abstract":"<p><p>This study aimed to gain insights into the dynamic proteome changes and underlying molecular mechanisms of de/remyelination in a cuprizone model, a widely used preclinical model of multiple sclerosis (MS). Longitudinal sampling of control or cuprizone-treated mouse brains was executed at 6 time points over 6 weeks. Data analysis included 8489 quantified proteins. Differential proteomic and GO analyses revealed that 5.9% of the quantified proteome was altered, including reported and novel de/remyelination-relevant protein changes and underlying pathways. We found that oligodendrocyte proteins (Fa2h and Ugt8) were significantly changed during demyelination, suggesting that dysregulated sphingolipid metabolism in MS may stem from oligodendrocyte pathology. Importantly, we showed that the cholesterol biosynthesis pathway was the most enriched biological process in a subset of significantly changed proteins, where myelination was highly enriched. We further validated the changes in the cholesterol biosynthesis pathway through targeted GC-MS analysis of intermediate sterols, supporting the critical role of cholesterol biosynthesis in de/remyelination. Unexpectedly, changes of myelin-associated proteins, Mbp and Plp1, were minimal, while Ermn showed significant reduction tracking with demyelination, indicating that some myelin protein changes are more sensitive to demyelination. Together with a list of significantly altered proteins, the results of this study could benefit future remyelination research.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping the Interactome of OSCC Prognostic-Associated Proteins NDRG1 and PGK1 Through Proximity Labeling Using TurboID. 使用TurboID通过邻近标记绘制OSCC预后相关蛋白NDRG1和PGK1的相互作用组
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-04-30 DOI: 10.1021/acs.jproteome.4c01039
Guilherme A Câmara, Sami Yokoo, Daniela C Granato, Fernando M Simabuco, Helder V Ribeiro-Filho, Reynaldo M Melo, Bianca A Pauletti, Edson G Nascimento Filho, Romênia R Domingues, Adriana Franco Paes Leme
{"title":"Mapping the Interactome of OSCC Prognostic-Associated Proteins NDRG1 and PGK1 Through Proximity Labeling Using TurboID.","authors":"Guilherme A Câmara, Sami Yokoo, Daniela C Granato, Fernando M Simabuco, Helder V Ribeiro-Filho, Reynaldo M Melo, Bianca A Pauletti, Edson G Nascimento Filho, Romênia R Domingues, Adriana Franco Paes Leme","doi":"10.1021/acs.jproteome.4c01039","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01039","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer, comprising over 90% of all oral malignancies worldwide. The identification of diagnostic and prognostic markers for OSCC is crucial for improving patient outcomes, as early detection and treatment are critical for the successful management of this disease. Previously, we demonstrated that <i>N-myc downstream-regulated gene 1</i> (NDRG1) and <i>phosphoglycerate kinase 1</i> (PGK1) are prognostic markers for OSCC; however, their role in OSCC development remains unclear. To investigate this, we used TurboID-based proximity labeling to identify the interactomes of NDRG1 and PGK1 in HEK293 cells. Herein, protein abundance patterns from three time points were used for clustering 364 proteins with a \"fast\" or \"slow\" response to biotin. Of these, 65 proteins were also identified in neoplastic islands of OSCC patients from our previous study, and 28 of these proteins have their gene expression associated with prognostic features, including death, metastasis, and relapse. PRM-MS enabled the quantification of 17 of these proteins, providing further evidence of their presence in the OSCC prognostic interactome. Finally, we characterized a prognostic-associated interactome composed of 28 proteins, which enabled the prioritization of candidates that can be further explored in OSCC progression. The mass spectrometry data generated in this study have been deposited in ProteomeXchange with the data set identifier PXD048046.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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