Proteomics最新文献

{"title":"Top-Down CSF Peptidomics Reveals Disease-Associated Peptide Signatures and Oxidative Modifications in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.","authors":"Cristina Contini, Lorena Lorefice, Greca Lai, Alessandra Schirru, Giorgia Zodio, Tiziana Cabras, Alessandra Olianas, Giacomo Diaz, Eleonora Cocco, Barbara Manconi","doi":"10.1002/pmic.70188","DOIUrl":"https://doi.org/10.1002/pmic.70188","url":null,"abstract":"<p><p>Multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD) are inflammatory demyelinating diseases of the CNS whose diagnosis is mainly based on clinical evidence, magnetic resonance imaging, and the analysis of cerebrospinal fluid (CSF). Current approaches provide only partial insight into disease-related biological processes, thus the need for deeper characterization of CNS-derived molecular signatures has emerged. Here, we applied a high-resolution top-down peptidomic approach in CSF from treatment naïve patients with CIS, relapsing-remitting multiple sclerosis (RRMS), NMOSD, and non-inflammatory neurological controls. The goal was to characterize their CSF endopeptidome, unravel insights into disease-associated proteolytic remodeling and molecular signatures not accessible through conventional proteomic approaches. 381 endogenous peptides were identified, including a substantial proportion of previously unreported sequences and oxidative PTMs. Quantitative analyses revealed disease-associated alteration of the CSF endopeptidome. A newly characterized C-terminal peptide derived from secretogranin-5 progressively decreased from CIS to RRMS and represented the most informative feature for discriminating patients using random forest (RF) analysis. In contrast, NMOSD patients exhibited a distinct profile characterized by widespread peptide reduction and decreased level of oxidation. Overall, these findings support the CSF endopeptidome as a biologically informative molecular layer associated with secretory pathway alteration, PTMs, and intrathecal inflammation. SIGNIFICANCE OF THE STUDY: Top-down peptidomics directly captures endogenous peptides and their native PTMs, providing information on proteolytic processing, that is lost in conventional digestion-based workflows or immune-based targeted approaches. In this top-down exploratory study, we characterized for the first time the CSF endopeptidome of treatment-naïve patients with CIS, RRMS stratified by oligoclonal-band (OCBs) status, NMOSD, and non-inflammatory neurological controls. The results revealed disease-associated patterns of granin-, osteopontin-, proSAAS-, and fibrinogen-derived peptides, especially for oxidative derivatives. A newly characterized C-terminal secretogranin-5 peptide showed a progressive cross-sectional decrease across the CIS and RRMS groups and contributed strongly to group classification, whereas NMOSD was characterized by widespread peptide depletion and a lower representation of oxidized peptide species. These findings support the CSF endopeptidome as a complementary molecular layer for investigating regulated proteolysis and redox-dependent alteration in inflammatory demyelinating disorders and identify peptide candidates for future validation in independent cohorts.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70188"},"PeriodicalIF":4.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: A Non-Metaproteomics Researchers' View on Metaproteomics in Microbiome Research.","authors":"","doi":"10.1002/pmic.70187","DOIUrl":"https://doi.org/10.1002/pmic.70187","url":null,"abstract":"","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70187"},"PeriodicalIF":4.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-Resolved Effects of Cold Atmospheric Plasma on E. coli GW-AmxH19 Transcriptome and Proteome in an Emulated Wastewater Environment.","authors":"Jörg Bernhardt, Dominik Schneider, Julia Rielicke, Susanne Sievers, Veronika Hahn, Mechthild Bömeke, Anja Poehlein, Dirk Albrecht, Juergen F Kolb, Katharina Riedel, Rolf Daniel, Daniela Zühlke","doi":"10.1002/pmic.70186","DOIUrl":"https://doi.org/10.1002/pmic.70186","url":null,"abstract":"<p><p>Cold atmospheric plasma (CAP) is effective against a variety of microorganisms. Here, we described effects on an Escherichia coli strain isolated from hospital wastewater caused by treatment with physical plasma. E. coli GW-AmxH19 was incubated in artificial wastewater and treated for 15 min with CAP. Transcriptomes and proteomes were monitored at different time points within a 24 h period to differentiate between immediate physiological responses and adaptations in the recovery phase. Reduction of viable cells was on average at 90%. The short-term response of the surviving cells to physical plasma aims at repairing and protecting cellular structures from plasma-induced damages, mainly provoked by reactive oxygen and nitrogen species. Notably, CAP induced a temporary transcription of genes from a conjugative plasmid carrying antibiotic resistance determinants. The late response during recovery phase is dominated by a massive activation of two prophages turning cold plasma treatment into a novel possible strategy to induce the lytic cycle of prophages. This study is the first report on the combined analysis of transcriptional and translational effects of CAP on an environmental bacterial isolate in a time-resolved manner. Chances and risks of considering CAP as an additional purification step in wastewater treatment plants to reduce the spread of pathogens and antibiotic resistances into the environment are depicted and discussed.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70186"},"PeriodicalIF":4.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage-Resolved Proteomic and Structural Insights Into Apocarotenoid Biosynthesis During Saffron (Crocus sativus) Flower Development","authors":"Namita Muduli,&nbsp;Pabitra Mohan Behera,&nbsp;Suchitrarani Sahoo,&nbsp;Luna Samanta,&nbsp;Khirod Kumar Sahoo","doi":"10.1002/pmic.70151","DOIUrl":"10.1002/pmic.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>Saffron (<i>Crocus sativus</i> L.) is one of the world's most valuable spices, renowned for its distinctive aroma, flavor, and pharmacological properties derived from apocarotenoids such as crocin, picrocrocin, and safranal, which accumulate in the stigmas during flower development. Despite their economic and medicinal importance, the molecular regulation of apocarotenoid biosynthesis across floral developmental stages remains poorly understood, particularly at the proteomic level. To address this gap, we applied an LC–MS/MS–based proteomic approach combined with bioinformatic and structural analyses to characterize stage-specific protein expression across five developmental stages: corm with floral shoot buds (A1), flower inside the sheath (S1), just outside the sheath (S2), flower at unopened state (S3), and flower at opened state (S4). Differential abundance analysis, gene ontology enrichment, STRING-based protein–protein interaction networks, KEGG pathway mapping, and structural modeling identified 57 developmentally regulated proteins linked to stigma differentiation and apocarotenoid metabolism. Stage-specific protein sets comprising 128 (A1), 44 (S1), 38 (S2), 29 (S3), and 29 (S4) proteins were selected using stringent statistical thresholds and validated through Limma-based differential expression analysis. Key enzymes, including PSY2, CCD2, ALDH2B4, and UGT707B1, emerged as central regulators of apocarotenoid biosynthesis during floral maturation. Overall, this study provides a comprehensive proteomic framework underlying stigma development and apocarotenoid accumulation in saffron, offering valuable molecular targets for improving metabolite yield and quality. The data supporting this study have been deposited in the ProteomeXchange repository under the identifier PXD076029.</p>\u0000 </div>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"46-59"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-Wide Dissection of Cachexia-Inducing Evolution in a Paired Human Neuroendocrine Carcinoma Cell Line Model","authors":"Julia Osaki,&nbsp;Yomogi Shiota,&nbsp;Kazuyoshi Yanagihara,&nbsp;Sumio Ohtsuki,&nbsp;Tadashi Kondo","doi":"10.1002/pmic.70153","DOIUrl":"10.1002/pmic.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer cachexia is a devastating systemic syndrome, yet tumor-intrinsic programs that enable cachexia induction remain poorly defined. Here we dissect cachexia-inducing tumor evolution using a uniquely paired model derived from a rare human duodenal neuroendocrine carcinoma, in which repeated in vivo passaging converts a non-cachexia-inducing cell line (TCC-NECT-2) into a cachexia-inducing derivative (AkuNEC). AkuNEC xenografts reproducibly induced progressive body weight loss, whereas TCC-NECT-2 xenografts did not. Using data-independent acquisition (DIA) proteomics, we quantified the proteomes of the paired cell lines and their matched xenograft tumors and performed complementary comparisons (cell line–to–cell line, cell–to–tumor within each lineage, and tumor–to–tumor). Proteomic profiling revealed robust divergence between TCC-NECT-2 and AkuNEC cells in vitro, and extensive remodeling upon xenograft formation in both lineages. Importantly, cachexia-inducing tumors displayed lineage-specific in vivo remodeling and an in vivo tumor proteome enriched for epithelial–mesenchymal transition, hypoxia, and cholesterol homeostasis, whereas no significant pathway enrichment was detected among proteins decreased in AkuNEC tumors under the applied false discovery rate (FDR) threshold. These results establish cachexia as an acquired tumor phenotype shaped by in vivo selection and provide a proteome-wide resource for prioritizing tumor-intrinsic candidates for future functional studies.</p>\u0000 </div>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"73-83"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light-Induced Proteomic Changes in Pseudomonas aeruginosa Biofilms","authors":"Lipi Das,&nbsp;Kelly N. Eckartt,&nbsp;Alexa Price-Whelan,&nbsp;Lewis M. Brown,&nbsp;Lars E. P. Dietrich","doi":"10.1002/pmic.70160","DOIUrl":"10.1002/pmic.70160","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Pseudomonas aeruginosa</i> is highly adaptable to environmental cues, including light. While specific light-responsive mechanisms have been studied in <i>P. aeruginosa</i>, the effects of light on biofilm proteomes remain unclear. Here, we employed quantitative proteomics to examine responses to white and red light in P. aeruginosa PA14 wild-type and bacteriophytochrome BphP null (<i>ΔbphP</i>) biofilms.</p>\u0000 <p>Biofilms were cultivated under dark, white, and red light conditions. Peptides were analyzed using an Orbitrap Exploris 240 mass spectrometer. Across five experimental groups (n = 3), 3,875 proteins were identified and quantified with &gt;99.9% data completeness and CV &lt;15%. Of these, 862 proteins were differentially expressed (&gt;1.5-fold, FDR 5%) in response to light.</p>\u0000 <p>Red light induced the upregulation of proteins involved in osmotic stress response and carbohydrate metabolism in wild-type biofilms. Catalase KatE was upregulated &gt;20-fold, while catalase KatA was suppressed, indicating a differential oxidative stress response. These patterns were reversed in a <i>ΔbphP</i> mutant, suggesting BphP-dependent regulation. Light exposure also reduced expression of the virulence factors elastase (LasB) and protease LasA (LasA). Several targets of the AlgB/RpoN network, including the anti-sigma factor MucA, showed BphP-linked changes.</p>\u0000 <p>These findings confirm the role of BphP as a key regulator of light-mediated proteomic adaptation in <i>P. aeruginosa</i> biofilms.</p>\u0000 </div>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"117-130"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unspecific Molecular Adsorption (UMA) Sample Preparation Method for Bottom-up and Whole Protein Analysis: The Foundation","authors":"Alexandre Zougman","doi":"10.1002/pmic.70149","DOIUrl":"10.1002/pmic.70149","url":null,"abstract":"<p>The protein sample preparation methods for shotgun proteomics are nowadays well-established unlike the ones for whole protein analysis. The goal of my work has been to create a simple methodology which provides a single uncomplicated sample preparation tool for these two fields. Nowadays the bulk of proteomics work is done using detergents for protein solubilization. The presented concept, which is based on unspecific adsorption of protein molecules on wide pore materials, allows for protein capture and clean-up from solutions of the most commonly used sodium dodecyl sulfate detergent. It could also be applied to proteins in detergent-free solutions. After the capture and clean-up, proteins could be either cleaved for the downstream peptide analysis or eluted for the whole protein analysis. If required, the eluted whole proteins could be recaptured and cleaved into peptides. Depending on the experimental goals, the sample preparation device could be fitted with embedded proteolytic enzymes to simplify routine sample processing and/or reversed phase media for the downstream peptide or protein separation.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"6-15"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information: Proteomics 10'26","authors":"","doi":"10.1002/pmic.70183","DOIUrl":"https://doi.org/10.1002/pmic.70183","url":null,"abstract":"","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"1-5"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-Scale Mining of Metal-Associated Proteins of Monkeypox Virus","authors":"Nimita Kant,&nbsp;Anand Kumar Bharti,&nbsp;Shailender Kumar Verma","doi":"10.1002/pmic.70158","DOIUrl":"10.1002/pmic.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Metal ions are crucial for viral processes like replication, structural integrity and immune modulation, despite that the metalloproteome of Monkeypox virus (MPXV) remains largely unexplored. Monkeypox virus is a re-emerging zoonotic Orthopoxvirus with a 197 kb genome encoding over 183 proteins. Here, in this report we aimed to identify and explore the metal-associated proteome of the MPXV. Derived from employing a structure driven pipeline, followed by the functional annotation, the subcellular localization, evolutionary aspect, and structural validation with the established experimental evidences. Yielded a set of approximately 21 % high-confidence putative metal-associated proteins with a potential as metal-binding proteins. Functional annotation, Gene Ontology (GO) enrichment, and KEGG Orthology (KO) term assignment also revealed significant enrichment of pathways primarily related to functions such as, viral replication, genome maintenance, transcription, virion assembly, and host immune modulation. These metal-associated proteins are hypothesized to perform critical biological roles throughout the viral life cycle and pathogenesis. This includes nucleotide metabolism, transcriptional regulation, redox balance and immune evasion, and virion morphogenesis. These findings were further strengthened by subcellular localization analysis, which predicts the presence of metalloproteins within MPXV and its viral factories. Further, suggesting the spatial distribution of various metals and its utilization in the host organism. Facilitating the activities from viral attachment, entry, replication, transcription, viral assembly, and release as either mature virion (MV) or intracellular mature virion (IMV). Comparison and mapping these identified metal-associated MPXV proteins to Vaccinia virus followed by the virus-host network analysis highlighted the proposed role of metal-associated proteins within conserved Orthopoxvirus interaction pathways.</p>\u0000 </div>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"96-116"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Extracellular Vesicle Proteins as Predictive Biomarkers for Developing Type 1 Diabetes","authors":"Panshak P. Dakup,&nbsp;Lisa M. Bramer,&nbsp;Athena Schepmoes,&nbsp;Ivo Diaz Ludovico,&nbsp;Javier Flores,&nbsp;Raghavendra G. Mirmira,&nbsp;Bobbie-Jo M. Webb-Robertson,&nbsp;Thomas O. Metz,&nbsp;Emily K. Sims,&nbsp;Ernesto S. Nakayasu","doi":"10.1002/pmic.70148","DOIUrl":"10.1002/pmic.70148","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Plasma extracellular vesicles (EVs) are considered excellent sources for biomarker discovery since they carry signatures of their cellular origin and disease processes. In this paper, we evaluate the potential of plasma EV proteomics analysis for identifying predictive biomarkers of developing type 1 diabetes (T1D), which results from autoimmune destruction of insulin-producing β cells in the islet. We used strong anion exchange beads (Mag-Net) to capture plasma EVs from 19 donors with islet autoimmunity (diagnosed by circulating autoantibodies against islet proteins—AAB+) versus 17 control individuals and analyzed their protein cargo by mass spectrometry. The analysis identified and quantified 5,480 proteins, a 3.2-fold increase in proteome coverage compared to our previous T1D biomarker proteomics study that used whole plasma depleted of the 14 most abundant proteins. The Mag-Net approach also detected 1306 out of the 1717 proteins (76%) that we previously verified as EV proteins. Statistical tests revealed 448 proteins to be differentially abundant in AAB+ versus control volunteers, including 69 previously verified EV proteins. A functional-enrichment analysis resulted in overrepresentation of 25 pathways among the differentially abundant proteins, including pathways related to autoimmune response and lipid metabolism. The capacity of this data to predict AAB+ was tested with a machine learning analysis using a random forest model, resulting in a receiver operating characteristic-area under the curve of 0.81. Overall, our study indicates that plasma EV proteomics analysis can be an exciting approach for studying biomarkers for developing T1D.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance of the Study&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Type 1 diabetes (T1D) is a disease characterized by the body's inability to produce insulin and consequently, to control blood glucose levels. Despite the initial trigger being unclear, the disease development process involves an autoimmune response to the islets of Langerhans, resulting in the death of insulin-producing β cells. There is no cure for the disease, and treatment relies on exogenous administration of insulin. Therefore, preventive therapies that block the autoimmune process are attractive for treating T1D. In fact, anti-CD3 antibody (Teplizumab) delays the onset of T1D by 2 years by targeting T cells. Predictive biomarkers for developing T1D are needed to aid the development and implementation of new therapies and to identify the initial trigger and mechanisms of the islet autoimmune process. In this paper, we assess the potential of plasma extracellular vesicle (EV) proteomics analysis for identifying predictive biomarkers of T1D. Our results show excellent potential of the approach, opening opportunities to perform broader studies to identi","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"26 10","pages":"24-30"},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}