Sean A. Gile, Janet Rogers, Maurie Balch, Sudhakar Voruganti, Robert L. Matts, Steven D. Hartson
{"title":"Ten Non-N-Terminal-Domain Inhibitors of the Hsp90 Chaperone Machine Fail to Elicit Canonical Proteome-wide Responses in Jurkat Leukemia Cells","authors":"Sean A. Gile, Janet Rogers, Maurie Balch, Sudhakar Voruganti, Robert L. Matts, Steven D. Hartson","doi":"10.1021/acs.jproteome.6c00387","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00387","url":null,"abstract":"<p>Heat shock protein90’s (Hsp90) roles in cancer have promptedthe development of small-molecule inhibitors that target its N-terminalATP-binding pocket. Moreover, numerous alternative Hsp90 inhibitors(AHI) have been developed to target other sites of the Hsp90 chaperonecomplex. Alternative Hsp90 inhibition is typically validated in livingcells by assaying the inhibitor’s impact on a small numberof select Hsp90 client proteins. Here, we expand these traditionalcharacterizations by orders of magnitude, measuring changes in theproteomes of Jurkat cells treated with 10 different AHI compounds(ailanthone, celastrol, clorobiocin, coumermycin A1, daurisoline,derrubone, gambogic acid, garcinol, β-lapachone, and α-mangostin).By comparing these changes to those induced by the N-terminal Hsp90inhibitor NVP-AUY922, we find that none of our 10 AHI compounds inducethe canonical changes characteristic of N-terminal Hsp90 inhibition.Instead, six compounds appear to antagonize mitochondrial processes,while the other four demonstrate individual mechanistic profiles.We conclude that none of these 10 AHI compounds induce apoptosis inJurkat cells via Hsp90 inhibition. Because these compounds have beenpreviously advanced as Hsp90 inhibitors, results here indicate thatinsular client depletion assays are inadequate to the task of validatingHsp90 inhibition in living cells.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4831–4846"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890331","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":"Serum Proteomic Profiling Reveals Renin-Associated Immune and Cytoskeletal Dysregulation in Post-COVID-19 Condition Patients with Secondary Adrenal Insufficiency","authors":"Guirong Bai, Xiaomin Xie, Wenrui Ji, Yanting He, Li Zhang, Huan Li, Yazhi Yang, Yawen Wu, Siqi Pei, Ling Li, Rui Ping","doi":"10.1021/acs.jproteome.5c01054","DOIUrl":"10.1021/acs.jproteome.5c01054","url":null,"abstract":"<p>Post-COVID-19 condition (PCC) with secondary adrenalinsufficiency(SAI) involves multiorgan dysfunction, potentially linked to renin−angiotensin−aldosteronesystem dysregulation. The molecular basis of renin-associated pathologyremains unclear. Here, PCC+SAI patients were stratified by uprightrenin into low- (<38.8 pg/mL) and high-renin (≥38.8 pg/mL)groups. Clinical, endocrine, and proteomic analyses were performed.We found that high-renin patients showed increased BMI, lipids, renin,and aldosterone, but reduced aldosterone-to-renin ratio. Proteomicannalysis identified 20 differentially expressed proteins (DEPs), including17 upregulated and 3 downregulated proteins in Ren-H patients. Functionalannotation revealed that 15 DEPs were immune-related (e.g., APOC4,APOE, C4BPA, CFAH, CFHR3, PF4V, PLF4), while FLNA and COF1 representedcytoskeletal proteins. These DEPs were primarily involved in immuneresponse, complement and coagulation cascades, and MAPK signalingpathways. Correlation analyses indicated that upright renin was positivelycorrelated with complement-related proteins and platelet-derived immunefactors, while cytoskeletal proteins (FLNA, COF1) showed positiveassociations with serum Na+ levels. Additionally, white blood celland platelet counts were positively correlated with the majority ofDEPs. In conclusion, exploratory proteomic analyses suggest that elevatedupright renin in PCC+SAI may be associated with immune dysregulation,complement activation, and cytoskeletal remodeling, offering novelinsights into the endocrine−immune interactions driving postviralsequelae.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4485–4495"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890363","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}
Punyatoya Panda, Rodrigo Mohallem, Rita de Kassia Rodrigues Bezerra Filgueira, Niwako Ogata, Uma K. Aryal
{"title":"Urine and Serum Proteome and Lipidome Analysis of Naturally Aging Feline Species","authors":"Punyatoya Panda, Rodrigo Mohallem, Rita de Kassia Rodrigues Bezerra Filgueira, Niwako Ogata, Uma K. Aryal","doi":"10.1021/acs.jproteome.6c00247","DOIUrl":"10.1021/acs.jproteome.6c00247","url":null,"abstract":"<p>Aging in companionanimals such as cats closely relatesto humanaging in environmental exposures and disease manifestation, providinga valuable model for identifying biomarkers of age-associated decline.This study provides a combined proteomic and lipidomic analysis ofserum and urine from naturally aging domestic cats aged 3.8–16years, grouped as adult, old, and senior, to identify age-relatedmolecular changes across biofluids. Label-free quantitative proteomicsidentified 901 urinary and 238 serum proteins, with 75 urinary proteinssignificantly altered with age that are linked to kidney disease,hypertension, neurodegeneration, and metabolic disorders. In contrast,only six serum proteins differed significantly between adult and old/seniorcats, including decreased Apolipoprotein A-I (APOA1) in seniors, aprotein linked with cognitive function in aging. Untargeted lipidomicsrevealed increases in specific serum triacylglycerols, phosphatidylcholines(PCs), and sphingomyelins, while urinary lipid profiles showed limitedage-related changes, with some PCs decreasing, and diacylglycerolsincreasing with age. These results demonstrate distinct systemic andrenal molecular remodeling during feline aging and highlight the utilityof integrated omics analyses of biological fluids for identifyingmolecular alterations relevant to both feline and human aging.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4719–4733"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890366","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":"Reframing Proteomics Measurement: Super Mass Spectrometry Framework and the Role of Delayed Electrospray Ionization Technique","authors":"Mazdak Taghioskoui","doi":"10.1021/acs.jproteome.5c00971","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00971","url":null,"abstract":"<p>Dynamic range, repeatability, and reproducibility remainthe centrallimitations of data-independent acquisition (DIA) proteomics. Currentworkflows emphasize protein group identification counts and throughput,but these metrics mask the fundamental measurement challenge: generatinga repeatable, reproducible, high-fidelity, and relatively completedigital representation of complex proteomes. In particular, plasmaproteomics spans more than 10 orders of magnitude in protein abundance,far exceeding the capacity and dynamic range of any single mass spectrometer.Incremental advances have not closed this gap. In this Perspectivesarticle, I introduce the Super Mass Spectrometry framework and thenhighlight the Delayed Electrospray Ionization (Delayed-ESI) technique,as a practical approach to address these limitations. By producingcompositionally identical but temporally staggered ion beams, theDelayed-ESI technique enables deterministic remeasurement of the sameanalyte profile, supporting various novel strategies to improve analyticalfigures of merit. While recent implementations of the Delayed-ESItechnique have emphasized throughput, I argue that the broader valueof the Delayed-ESI technique lies in extending dynamic range and improvingrepeatability and reproducibility─objectives that should takeprecedence if proteomics is to evolve into a robust measurement sciencecapable of supporting population-scale proteomics studies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4393–4406"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890301","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}
Sherifdeen Onigbinde, Joy Solomon, Vishal Sandilya, Oluwatosin Daramola, Mojibola Fowowe, Moyinoluwa Adeniyi, Firas Kobeissy, Stefania Mondello, Ava M. Puccio, Yehia Mechref
{"title":"Development of a High-Sensitivity Glycoproteomics Approach for Fc-Specific Quantification of IgG Core Fucosylation in Traumatic Brain Injury","authors":"Sherifdeen Onigbinde, Joy Solomon, Vishal Sandilya, Oluwatosin Daramola, Mojibola Fowowe, Moyinoluwa Adeniyi, Firas Kobeissy, Stefania Mondello, Ava M. Puccio, Yehia Mechref","doi":"10.1021/acs.jproteome.5c01154","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c01154","url":null,"abstract":"<p>Traumatic brain injury (TBI) triggerscomplex neuroinflammatorycascades that involve sustained immune activation and dysregulatedantibody effector functions. Immunoglobulin G (IgG) Fc <em>N</em>-glycosylation, particularly core fucosylation, critically modulatesimmune signaling through altered Fcγ receptor (FcγR) interactions;however, its role in TBI remains unexplored. Here, we developed ahigh-sensitivity, mass spectrometry-based glycoproteomics method forthe systematic analysis of IgG Fc core fucosylation dynamics followingTBI. The approach integrates Fc-specific enzymatic truncation withGlycINATOR (EndoS2) and tryptic digestion, followed by high-resolutionLC–MS/MS profiling, enabling confident identification of truncatedFc glycopeptides. Furthermore, a targeted parallel reaction monitoring(PRM) strategy allowed direct quantification of core fucosylated andafucosylated glycopeptides from 10 μg of crude serum protein,eliminating the need for IgG purification. Our results reveal time-dependentand subclass-specific remodeling of IgG Fc fucosylation postinjury,characterized by an overall reduction in fucosylated species and arelative increase in afucosylation. Collectively, this study establishesa scalable analytical platform for Fc-specific glycosylation profilingand identifies IgG core fucosylation as a candidate molecular indicatorof immune dysregulation in TBI, providing new insights into post-traumaticimmune regulation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 9","pages":"4470–4484"},"PeriodicalIF":3.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890330","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}
Aziz Belkadi, Gaurav Thareja, Nisha Stephan, Anna Halama, Karsten Suhre
{"title":"Size-Resolved Lipoprotein Fatty Acid Content as a Novel Nuclear Magnetic Resonance-Derived Trait Specifically Associates with Genetic Variants That Control Fatty Acid Metabolism","authors":"Aziz Belkadi, Gaurav Thareja, Nisha Stephan, Anna Halama, Karsten Suhre","doi":"10.1021/acs.jproteome.6c00107","DOIUrl":"10.1021/acs.jproteome.6c00107","url":null,"abstract":"<p>Population-levelnuclear magnetic resonance (NMR)-based lipoproteinprofiling is a key tool for investigating dysregulated lipoproteinmetabolism and its role in cardiovascular disorders. However, associationswith size-resolved lipoprotein composition readouts are difficultto dissect, as these traits are often highly correlated. Derived variablescan therefore be more relevant to biological interpretation. Here,we show that the total fatty acid (FA) content of the lipoproteinsderived from their lipid headgroup concentrations using the formulaFA = 3TG + 2PL + CE strongly correlates (Spearman rho = 0.98) withthe independently measured total fatty acid content. This observationis not self-evident since these variables are determined using differentportions of the NMR spectrum. Using NMR data acquired on the Nightingaleplatform for 274,303 UK Biobank (UKB) participants and genetic associationsas a readout, we then show that this relationship also holds at thesize-resolved lipoprotein level. We identified eight gene loci wherethe proposed FA variables display a significantly stronger geneticassociation signal than that of the corresponding lipid headgroupvariables. Five of these loci (LIPC, LIPG, PLB1, LPL, and APOC3) havea direct function in FA metabolism. Including computed size-resolvedFA variables may therefore improve the biological interpretation offuture studies based on Nightingale’s data.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 8","pages":"4062–4071"},"PeriodicalIF":3.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343428","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}
Léa Réthoré, Benjamin Barré, Anne-Laure Guihot, Linda Grimaud, Coralyne Proux, Alice Boissard, Cécile Henry, Catherine Guette, François Guillonneau, Daniel Henrion, Christian Legros, Claire Legendre
{"title":"Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow","authors":"Léa Réthoré, Benjamin Barré, Anne-Laure Guihot, Linda Grimaud, Coralyne Proux, Alice Boissard, Cécile Henry, Catherine Guette, François Guillonneau, Daniel Henrion, Christian Legros, Claire Legendre","doi":"10.1021/acs.jproteome.5c01254","DOIUrl":"10.1021/acs.jproteome.5c01254","url":null,"abstract":"<p>Endothelial cells (ECs) are key regulators in vascularhomeostasis,and their physiological state depends on hemodynamic forces producedby the blood flow. Laminar shear stress (LSS) maintains endothelialintegrity, whereas oscillatory shear stress (OSS) leads to endothelialdysfunction and subsequently to cardiovascular disease. Here, we delineatedthe proteomic signatures of human umbilical vein endothelial cells(HUVECs) exposed to a protective flow (LSS) or a disturbed flow (OSS)in comparison to static conditions, using trapped ion mobility spectrometrycoupled with parallel accumulation-serial fragmentation. OSS inducedlimited changes in cell morphology and the proteomic profile, whereasLSS triggered major modifications in cell shape and a proteomic signaturerelated to the cell surface and extracellular matrix. Membrane subproteomicprofiling confirmed the identification of membrane effectors involvedin flow-mediated responses and in silico integrating promoter analysissuggested Krüppel-like Factor 4 (KLF4) as an important transcriptionalregulator of this effector cluster. Using a novel EC model, TeloHAECs,we demonstrated that KLF4 likely contributes to LSS-induced alignmentand elongation by increasing the expression of <em>CD34</em>, <em>HEG1</em>, <em>PI16</em>, and <em>ITGB4</em> and that KLF4 is involved in <em>PI16</em> and <em>ITGB4</em> expression. Collectively, these findings provide a robust discoverydata set on EC proteomic profiles related to flow and a refined viewof KLF4-associated regulatory signatures at the level of membraneprotein–coding genes in response to LSS.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 8","pages":"3987–4004"},"PeriodicalIF":3.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389329","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}
Carly A. I. Twigg, Kathleen M. Madden, Kristin L. M. Boylan, Amy P. N. Skubitz, Stefani N. Thomas
{"title":"Protein Enrichment from Ascites Fluid Using Nanotrap Hydrogel Particle Technology","authors":"Carly A. I. Twigg, Kathleen M. Madden, Kristin L. M. Boylan, Amy P. N. Skubitz, Stefani N. Thomas","doi":"10.1021/acs.jproteome.6c00202","DOIUrl":"10.1021/acs.jproteome.6c00202","url":null,"abstract":"<p>Ascites fluid isa clinically relevant biological matrix commonlypresent in patients with high-grade serous ovarian carcinoma (HGSOC).Enrichment or depletion methods are required to compress the dynamicrange of the ascites fluid proteome prior to mass spectrometry (MS)-basedproteomic analysis. In this study, we evaluated the ability of NanotrapProtein Enrichment Affinity Kits (PEAK) to enable the MS detectionof lower-abundance proteins in ascites fluid in a biomarker discoveryworkflow. Nanotrap PEAK contains magnetic hydrogel nanoparticles (A,B, and C), whose complementary chemistries selectively isolate low-abundanceproteins while excluding high-abundance proteins to enhance the depthof proteome coverage. The Nanotrap particles have previously beenevaluated for plasma, serum, CSF, and urine protein enrichment butnot ascites fluid. The use of the Nanotrap particles resulted in >2–3×more identified proteins than the Neat ascites. An average of 61%of the proteins were enriched by the Nanotrap particles, whereas 39%were depleted. The maximum number of proteins identified among 10HGSOC-derived ascites samples processed using the Nanotrap particleswas 3480–4000 vs 1505 in the Neat samples. The use of Nanotrapparticles is a cost-efficient and readily scalable approach for MS-basedproteomic biomarker discovery studies in ascites fluid.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 8","pages":"4322–4332"},"PeriodicalIF":3.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417059","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}
Sander Heyndrickx, Robbin Bouwmeester, Arthur Declercq, Robbe Devreese, Magnus Palmblad, Wout Bittremieux, Tess AV Afanasyeva, Joel Lapin, Arzu Tugce Guler, Pierre-Olivier Schmit, Christine Carapito, Lennart Martens, Ralf Gabriels
{"title":"Instrument–Software Synergy in Proteomics: Systematic Evaluation across Mass Spectrometry Platforms, Search Engines, and Rescoring Methods","authors":"Sander Heyndrickx, Robbin Bouwmeester, Arthur Declercq, Robbe Devreese, Magnus Palmblad, Wout Bittremieux, Tess AV Afanasyeva, Joel Lapin, Arzu Tugce Guler, Pierre-Olivier Schmit, Christine Carapito, Lennart Martens, Ralf Gabriels","doi":"10.1021/acs.jproteome.6c00295","DOIUrl":"10.1021/acs.jproteome.6c00295","url":null,"abstract":"<p>Mass spectrometry-based proteomics has advanced throughparallelimprovements in instrumentation (mass spectrometers) and software(data analysis), yet whether these improvements interact synergisticallyor provide diminishing returns remains unclear. Here, we systematicallyevaluate instrument–software coevolution across eight massspectrometry platforms, three generations of search engines, and multiplerescoring approaches, yielding 72 unique instrument–softwarecombinations spanning from 2004 to 2024. Our results reveal that instrumentationand software improvements produce synergistic rather than substitutivebenefits. Here, machine learning-based rescoring consistently recoversidentifications from low-intensity precursors that produce noisier,more challenging spectra. Crucially, because of increased sensitivityand speed, modern instruments detect more low-intensity precursors,thereby increasing the population of challenging spectra for whichrescoring provides the greatest benefit. However, this expanded detectiondepth comes at a cost: recovered low-abundance peptides exhibit inherentlyhigher quantification error, creating a fundamental trade-off betweenproteome coverage and quantification accuracy. Together, these findingsprovide a systematic overview of how instrument and software advanceshave jointly shaped proteomics performance over the past two decades.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 8","pages":"4251–4261"},"PeriodicalIF":3.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443463","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}
Mauricio Quiñones-Vega, Patricia Sosa-Acosta, Giovanna Câmara Giudicelli, Mariléa Furtado Feira, Bibiana S. O. Fam, Nathan Araújo Cadore, Renan Cesar Sbruzzi, Fernanda Sales Luiz Vianna, Fábio C. S. Nogueira, Gilberto B. Domont
{"title":"Temporal Proteomic Profiling of Hospitalized COVID-19 Patients Reveals Prognostic Biomarkers","authors":"Mauricio Quiñones-Vega, Patricia Sosa-Acosta, Giovanna Câmara Giudicelli, Mariléa Furtado Feira, Bibiana S. O. Fam, Nathan Araújo Cadore, Renan Cesar Sbruzzi, Fernanda Sales Luiz Vianna, Fábio C. S. Nogueira, Gilberto B. Domont","doi":"10.1021/acs.jproteome.6c00129","DOIUrl":"10.1021/acs.jproteome.6c00129","url":null,"abstract":"<p>COVID-19 presents a wide spectrum of clinical outcomes,and earlyidentification of patients at high-risk for a worse disease prognosisremains a critical challenge. In this study, we performed a six-weeklongitudinal proteomic analysis of 197 plasma samples collected weeklyfrom 44 hospitalized COVID-19 patients. Temporal profiling revealed828 proteins with significant time-dependent abundance changes, clusteringinto an early acute-phase and inflammatory response group that graduallydeclined toward the cohort’s overall mean profile over timeand a group of late vesicle-mediated transport and antigen bindingthat were decreased in the first weeks. Global correlation mappingidentified six coregulated protein modules, notably including insulin-likegrowth factor binding proteins. Proteomic divergence between survivorsand nonsurvivors became pronounced from week 4 onward. The proteinsHPR, IGFALS, PF4, LPA, and COLEC11 achieved AUCs > 0.72 for mortalityprediction in the first 2 weeks, and an SVM model combining thesemarkers yielded an AUC of 0.801. These findings demonstrate that plasmaproteome trajectories capture dynamic host responses and generatecandidate prognostic markers, offering a promising strategy for riskstratification and guiding targeted interventions in COVID-19.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 8","pages":"4086–4098"},"PeriodicalIF":3.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682677","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}