{"title":"Proteomics Reveals Novel Biomarkers in the Blood for Sepsis Diagnosis","authors":"Zhenjun Fan, Meiling Chen, Ye Sun, Pingsen Zhao","doi":"10.1021/acs.jproteome.6c00385","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00385","url":null,"abstract":"<p>Early sepsis diagnosisin critically ill patients remains a majorunmet need. We employed a multiphase proteomic strategy integratingdiscovery by data-independent acquisition, targeted verification byparallel reaction monitoring, clinical confirmation with ELISA, andmachine learning to identify robust blood biomarkers. In discoveryand verification cohorts, three consistently downregulated proteins,α-2-HS-glycoprotein (AHSG), clusterin (CLU), and kallistatin(SERPINA4), were prioritized. A random forest model combining thesemarkers yielded an apparent area under the curve (AUC) of 0.94 inthe training cohort. Crucially, in a prospective evaluation of 143patients with suspected sepsis, representing the true test of generalizability,the model achieved an AUC of 0.87, significantly outperforming PCTand CRP, and correctly classified 73.0% of confirmed sepsis casesas high-risk. This triple-biomarker panel enables rapid, accurateearly detection of sepsis and offers a readily translatable diagnostictool for clinical practice.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"5884–5898"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330232","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}
John R. Yates, III, Éva Csősz, Claire E. Eyers, Jennifer Geddes-McAlister, Elaine Holmes, Ryan T. Kelly, Thomas Kislinger, Huilin Li, Magnus Palmblad, Suman S. Thakur
{"title":"From Identification to Integration: Twenty-Five Years of Proteomics and Metabolomics through the Pages of the Journal of Proteome Research","authors":"John R. Yates, III, Éva Csősz, Claire E. Eyers, Jennifer Geddes-McAlister, Elaine Holmes, Ryan T. Kelly, Thomas Kislinger, Huilin Li, Magnus Palmblad, Suman S. Thakur","doi":"10.1021/acs.jproteome.6c00542","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00542","url":null,"abstract":"<p>As the American Chemical Society marks its 150th anniversary,itis a fitting moment to reflect on how a young analytical discipline,proteomics, matured into a central pillar of the chemical and biologicalsciences and how the <em>Journal of Proteome Research</em> (<em>JPR</em>) chronicled and guided that transformation.Founded at the dawn of shotgun proteomics, <em>JPR</em> haspublished pivotal advances in separation, ionization, computationalinterpretation, quantitative strategies, and biological applications.In this Perspective, we trace that arc from the first near-completeeukaryotic proteomes through the quantitative and post-translationalera, the computational turn, and the current high-throughput, integrative,and artificial-intelligence-assisted phase. Along the way, we highlighthow the same infrastructure enabled mass spectrometry-based metabolomics,yielding an integrated framework for molecular phenotyping.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"5695–5705"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330326","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}
{"title":"Molecular Features of Heatstroke Revealed by Integrated Proteomics and Metabolomics","authors":"Daoyun Guo, Defeng Yin, Haili Li, Qin Guo, Yonglan Hu, Yu Zhang, Yingchun Hu, Kaiyu Jin, Liling Zhang","doi":"10.1021/acs.jproteome.5c00450","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00450","url":null,"abstract":"<p>Heatstroke is a criticalmedical condition marked byhyperthermia-inducedimmune dysregulation, endothelial damage, and organ dysfunction, yetits molecular mechanisms are not fully elucidated. In this study,serum samples from heatstroke (HS) patients and normal controls (NCs)were subjected to untargeted ultrahigh-performance liquid chromatography-tandemmass spectrometry (UHPLC-MS/MS) metabolomic and quantitative proteomicanalyses. Differential proteins and metabolites were identified andfurther analyzed through pathway enrichment, protein–proteininteraction, correlation, and integrated multivariate analyses. Comparedto NC, HS patients demonstrated 161 differential proteins (136 up-regulated,25 down-regulated) and 427 differential metabolites (330 up-regulated,97 down-regulated). The proteins B2M, MMP9, and APOB were identifiedas key hub proteins linked to immune activation, endothelial injury,and lipid metabolism. Metabolic changes were observed in kynurenine,purine, and mitochondrial energy metabolism pathways, while lipidmetabolites showed an inverse correlation with inflammatory proteins.Integrated principal component analysis (PCA) and canonical correlationanalysis (CCA) effectively distinguished HS patients from the NC.Through joint pathway analysis, 30 enriched KEGG pathways were identified,notably including cAMP signaling and arachidonic acid metabolism.These findings elucidate coordinated alterations in immune, vascular,and metabolic processes associated with heatstroke, and underscoreB2M, MMP9, and ANGPTL3 as potential molecular features warrantingfurther investigation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"5706–5719"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330335","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}
{"title":"Unveiling Cerebrospinal Fluid Protein Biomarkers in Pediatric Acute Lymphoblastic Leukemia Using a Proximity Extension Assay","authors":"Mahshid Moballegh Nasery, Réka Gergely, Nóra Kutszegi, Istvan Szegedi, Dániel János Erdélyi, Csongor Kiss, Éva Csősz","doi":"10.1021/acs.jproteome.6c00599","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00599","url":null,"abstract":"<p>Acute lymphoblastic leukemia (ALL) is a heterogeneouspediatricmalignancy where relapse and central nervous system (CNS) involvementremain critical challenges. We combined high-throughput proteomicsand machine learning (ML) to identify cerebrospinal fluid (CSF) biomarkersfor treatment response and CNS status. Proteomic profiling of 276proteins was performed on 82 CSF samples from 41 pediatric patientswith ALL at diagnosis (VD) and in remission (VR) using Olink’sproximity extension assay. Differentially abundant proteins (q-value< 0.05, |log2FC| > 0.5) were identified via the Wilcoxon test,and Random Forest, LASSO, and SVM-RFE algorithms were integrated toselect key predictive proteins for remission status and CNS involvement.Validation was performed using Pan-Cancer Atlas data sets. Remissionwas characterized by changes in ADGRG1, KYNU, CCL17, CD5, CD27, CXCL9,CXCL11, FASLG, GZMA, and TNFRSF9 between the two visits. Furthermore,distinct proteins associated with CNS involvement were shown, withCXCL9 and MMP7 being differentially abundant between CNS involvementgroups at both visits. Integrating Olink proteomics with ML identifiedmolecular signatures in ALL that have the potential to be consideredas biomarkers for monitoring treatment response and guiding personalizedtherapeutic strategies, shifting the focus toward Precision One Healthapproaches.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6276–6288"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330371","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}
Bo Wen, Kai Li, Michael Riffle, Michael J. MacCoss, Wout Bittremieux, William Stafford Noble
{"title":"CasanovoGUI: A Cross-Platform Desktop Application for Deep Learning-Based De Novo Peptide Sequencing with Casanovo","authors":"Bo Wen, Kai Li, Michael Riffle, Michael J. MacCoss, Wout Bittremieux, William Stafford Noble","doi":"10.1021/acs.jproteome.6c00617","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00617","url":null,"abstract":"<p>De novo peptide sequencingdetects peptides directlyfrom tandemmass spectra without a protein sequence database, and deep learninghas substantially advanced its performance. Casanovo, one such widelyused model, is distributed as a Python command-line program. Consequently,installation, GPU and dependency configuration, and manual parametrizationcan be challenging for many bench scientists and are a recurring sourceof errors. Interpreting and validating the resulting predictions posesa further challenge. We present CasanovoGUI, an open-source Java-baseddesktop application that makes all of Casanovo’s main analysisfunctions available through a point-and-click interface on Windows,macOS, and Linux. On first use, CasanovoGUI automatically installsa private Python environment and Casanovo with a GPU-matched build,requiring no prior software setup. The GUI provides access to Casanovo’sanalysis functions and configuration parameters, streams live progress,and integrates results interpretation: annotated spectra with per-residueconfidence scores in the PDV viewer and mismatch-tolerant mappingof de novo peptides back to a reference proteome. CasanovoGUI is availableat https://github.com/Noble-Lab/CasanovoGUI.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6514–6520"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330394","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}
Valeriy I. Postoenko, Mikhail V. Gorshkov, Mark V. Ivanov
{"title":"Comparison Study of Data Processing Workflows for Label-Free DIA Quantitative Proteomics","authors":"Valeriy I. Postoenko, Mikhail V. Gorshkov, Mark V. Ivanov","doi":"10.1021/acs.jproteome.6c00778","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00778","url":null,"abstract":"<p>Data processing tools for the data-independent acquisitionmethod,rapidly gaining popularity in proteomics in recent years, are cruciallyimportant for this method’s efficiency. Quite a number of them,serving both the identification and quantitation of proteins, havebeen developed over the past decade, yet the issue is still in itsinfancy, and the research on their comparison and integration is scarce.In this study, we collected four DIA search workflows─DIA-NN,DIA-Umpire, diaTracer, and MSFragger-DIA─as well as four proteinquantitation utilities─directLFQ, AlphaPeptStats, Triqler,and simple <em>t</em> test─to evaluate the efficienciesof quantitation workflows integrating these tools in different combinations.The combinations were evaluated in terms of the number of proteinidentifications, differential expression sensitivity, fold changeaccuracy, and quantitative false discovery rate control, using twospike-in benchmark data sets. The study provides insights into thecompatibility of the evaluated software pairs and practical recommendationsfor improving the data analysis pipeline for DIA proteomics.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6456–6462"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330220","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}
{"title":"Integrated Lipidomic and Energy Metabolomic Analyses Reveal the Cardioprotective Mechanisms of Meconopsis horridula Alkaloids in Heart Failure","authors":"Yao Zhao, Yanhong Li, Guiqin Liu, Jinping Fu, Junjun Han, Sencai Wang, Xiaojiao Chen, Xuguo Yang, Jie Zhang, Shengyan Wang, Xiangyang Li, Qiangqiang Jia","doi":"10.1021/acs.jproteome.6c00549","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00549","url":null,"abstract":"<p><em>Meconopsis horridula</em> Hook.f. &Thomson (MH) is a traditional Tibetan medicinal herb used to promoteblood circulation and treat cardiovascular disorders; however, itsactive constituents and cardioprotective mechanisms in heart failure(HF) remain poorly understood. In this study, liquid chromatography–massspectrometry was used to characterize the alkaloid profile of MH,and the cardioprotective effects of its alkaloid fraction were evaluatedin a doxorubicin-induced rat model of HF. A total of 26 alkaloidswere identified. Treatment with MH alkaloids significantly improvedcardiac function and attenuated myocardial injury in HF rats. To elucidatethe underlying mechanisms, quantitative lipidomics and targeted energymetabolomics analyses were performed. Compared with the model group,MH treatment altered multiple lipid and energy metabolites associatedwith ether lipid metabolism, glycerophospholipid metabolism, lipidand atherosclerosis, glyoxylate and dicarboxylate metabolism, andthe citrate cycle. Integrated pathway analysis identified NADH/ubiquinoneoxidoreductase complex assembly factor 6 (NDUFAF6), AMPK, ACC, GLUT4,ACOT1, and ATP2A as key regulatory nodes. Western blot analysis furthersupported the involvement of these proteins in MH-mediated metabolicremodeling. Collectively, these findings suggest that MH alkaloidsalleviate HF by partially restoring dysregulated glucose and lipidmetabolism and provide mechanistic insights into their cardioprotectiveeffects.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6315–6334"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330302","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}
{"title":"RNA-Adjusted TUFM Protein State Captures Mitochondrial Proteome Organization in Lung Adenocarcinoma","authors":"Xiaoyuan Weng, Yanqi Tang, Qianqian Li, Xiyin Huang, Jinsheng Wang, Jianqing Lin","doi":"10.1021/acs.jproteome.6c00814","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00814","url":null,"abstract":"<p>Matched transcriptome-proteome measurementscan reveal protein-stateinformation not represented by RNA abundance. We integrated four lungadenocarcinoma (LUAD) proteogenomic cohorts, two longitudinal osimertinibtranscriptomic systems, and DepMap CRISPR screens to test whetherthe TUFM protein captures coordinated mitochondrial proteome organizationbeyond TUFM RNA. In discovery LUAD, the RNA-adjusted TUFM proteinstate (TUFM_PT) added substantial explanatory information beyond itstranscript for mitochondrial-translation and oxidative-phosphorylation(OXPHOS) protein programs. Across three independent cohorts (<em>n</em> = 292), TUFM_PT replicated with pooled Spearman rho valuesof 0.564 and 0.620 for mitochondrial translation and OXPHOS, respectively,and ranked 40th and 23rd among 5,242 externally benchmarked RNA-adjustedprotein states. Associations persisted after copy-number, clinical,tumor-purity, and background-proteome adjustment. Highest-ranked humanTUFM_PT proteomic partners were enriched in an independent CRISPRcodependency network, including after the exclusion of prespecifiedmitochondrial genes, demonstrating cross-modal convergence at thenetwork tail. Longitudinal osimertinib data provided complementarytemporal context: early drug tolerance suppressed mitochondrial translationand OXPHOS transcripts, followed by later recovery without universalTUFM mRNA recovery. Together, these findings identify TUFM_PT as areproducible, network-embedded proteomic readout of mitochondrialorganization beyond TUFM RNA, while the longitudinal transcriptomesdefine the treatment-stage context rather than treatment-linked TUFMprotein dynamics.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6470–6482"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330378","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}
{"title":"Mapping the Metabolic Landscape of Aging: Advances in Spatial Metabolomics for Deciphering Heterogeneity in Age-Related Diseases","authors":"Gongchang Zhang, Fengjuan Hu, Yiping Deng, Yan Zhang, Tingting Huang, Meiling Ge, Lixing Zhou, Chenying Fu, Birong Dong","doi":"10.1021/acs.jproteome.6c00730","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00730","url":null,"abstract":"<p>Aging is marked by a profound paradox, and rising lifeexpectancyis not matched by an equivalent extension of healthspan. The coreof this disconnect lies in systemic metabolic dysregulation, a hallmarkof aging that traditional metabolomics, limited to tissue homogenates,fails to capture owing to its inherent spatial complexity. This reviewaddresses this critical gap by systematically elucidating how spatialmetabolomics is transforming geriatric medicine. We first outlinehow this technology maps organ- and cell-specific metabolic landscapes,revealing that aging disrupts metabolic networks in highly heterogeneous,region-specific patterns. We then detail its mechanistic role in decipheringthe metabolic origins of age-related diseases, from the toxic microenvironmentssurrounding amyloid plaques to the metabolic drivers of plaque instability.Furthermore, we explore its application in evaluating the spatialpharmacodynamics of antiaging interventions and discuss the path toclinical translation through integration with spatial multiomics andartificial intelligence. By shifting the paradigm from homogenatebiology to spatial biology, this review establishes spatial metabolomicsas an indispensable framework for deconvoluting the heterogeneityof aging. It provides the methodological foundation to map the healthyaging atlas and enables a move from simply understanding aging toactively shaping its trajectory through precision diagnostics andtargeted interventions.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"5681–5694"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330222","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}
Qiuhan Lu, Yi Zhang, Shiyu Yi, Yuwen Wu, Haolong Liu, Rui Dang, Sijia Fang, Rui Zhao, Xiangjun Du, Ting Hu, Chunguo Jiang, Yuxin Chen, Feng Jiao, Zhuoling An, Guozhi Jiang
{"title":"Sex-Specific Plasma Proteomic Alterations Underpin Distinct COVID-19 Progression and Post-COVID-19 Condition","authors":"Qiuhan Lu, Yi Zhang, Shiyu Yi, Yuwen Wu, Haolong Liu, Rui Dang, Sijia Fang, Rui Zhao, Xiangjun Du, Ting Hu, Chunguo Jiang, Yuxin Chen, Feng Jiao, Zhuoling An, Guozhi Jiang","doi":"10.1021/acs.jproteome.6c00524","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00524","url":null,"abstract":"<p>Sex differences in COVID-19 and its sequelae remain poorlyunderstood,which hinders targeted therapies. We performed plasma proteomic analysesof 69 hospitalized patients with COVID-19 and 30 healthy controlsfrom a prospective Chinese cohort. The UK Biobank and Mount SinaiBiobank were employed for validation and provided insights into theprogression mechanisms. Biological and tissue enrichment analysescharacterized sex-specific pathways and tissue-enriched proteins.We identified ANXA11, a molecular tether that physically links RNAgranules to lysosomal membranes to enable their long-distance transportand local translation, as a protein associated with male-specificsusceptibility to SARS-CoV-2 infection. Decreased ANXA11 protein levelswere linked to higher risk of infection in males, replicated in theUK Biobank. Sex-specific proteomic alterations revealed distinct biologicalresponses, including glycosylation-related pathways in females andcell adhesion, platelet-leukocyte interactions, and inflammatory responsesin males. Sex-specific protein changes were also associated with distinctpost-COVID-19 symptom profiles. ANXA11 was identified as a novelprotein associated with the male-specific susceptibility to SARS-CoV-2infection. Sex-specific protein changes revealed distinct mechanisticdifferences between male and female patients in COVID-19 progressionand may explain sex differences in post-COVID-19 conditions.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 11","pages":"6115–6125"},"PeriodicalIF":3.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330283","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}