J. Proteome Res. [JOURNAL]
Sun
200 papers
Identification of Age-Associated Circulating Proteins and Lipids in 3800 Comorbidity-Enriched Older Adults from Japan-Based Cohorts Using Olink Assays and MRM Mass Spectrometry.
Tokuoka SM, Hamano F, Kobayashi A … +4 more , Natsume T, Sugiyama M, Matsuda K, Oda Y
J Proteome Res · 2026 Jul · PMID 42398926 · Publisher ↗
Aging entails complex physiological changes, yet large-scale evidence among older Japanese individuals, especially those with comorbidities, remains limited. We analyzed serum and plasma samples from approximately 3800 J...
Aging entails complex physiological changes, yet large-scale evidence among older Japanese individuals, especially those with comorbidities, remains limited. We analyzed serum and plasma samples from approximately 3800 Japanese aged 40 years and older to identify age-associated proteins and lipids, focusing on reproducibility and robustness. Chemokines CXCL9 and CCL11 and phosphatidylcholines PC 31:0 and PC 32:0 were positively associated with age across five cohorts, whereas lysophosphatidylcholines LPC-LA and LPC-AA showed negative associations. These molecular relationships were consistently reproduced across serum and plasma matrices and replicated in independent cohorts. Cross-platform consistency was confirmed between Olink Target 96 (relative NPX) and Target 48 (absolute quantification), with direct validation in Cohort 2. To our knowledge, this is the largest study to demonstrate reproducibility of age-associated molecular biomarkers in a comorbidity-enriched Japanese population. The principal contribution is technical─defining a set of robust, cross-platform, cross-matrix biomarkers of aging in older adults. Unlike previous Western studies which focused on younger or healthier populations, this work establishes reproducibility and generalizability in real-world aging. These validated biomarkers provide a valuable reference for clinical and translational research, including risk stratification and biological age assessment in comorbidity-enriched settings.
Molecular Solution to the Paradox of Ancient Brain Preservation.
Morton-Hayward A, Flannery S, Berry P … +4 more , Vendrell I, Johansen A, Hansen M, Fischer R
J Proteome Res · 2026 Jul · PMID 42396998 · Publisher ↗
Brains decompose rapidly after death yet frequently survive in the archeological record, including >1300 cases of waterlogged, oxygen-poor graves in which the brain is the only preserved soft tissue amongst otherwise ske...
Brains decompose rapidly after death yet frequently survive in the archeological record, including >1300 cases of waterlogged, oxygen-poor graves in which the brain is the only preserved soft tissue amongst otherwise skeletonized remains. To address this paradox, we decayed mouse carcasses for six months in four burial regimes varying in water and oxygen availability, characterized the brain proteome by high-resolution liquid chromatography-tandem mass spectrometry using parallel data-dependent and -independent acquisition workflows at six intervals, and modeled >1.26 million peptide-specific decay trajectories to identify decay-prone and -resistant sequences. Oxygen availability exerted the main control on molecular fate: oxic burials produced widespread protein loss, whereas wet, hypoxic conditions favored retention of a distinctive subset of decay-resistant peptides. These surviving sequences were structurally ordered, enriched in redox-active residues and in regions that bind metals and lipids, and bore modification patterns consistent with radical-mediated oxidative cross-linking rather than fragmentation. By linking intrinsic tissue chemistry and environmental context, our results move brain preservation from anomaly to expectation: resolving why brains outlast other soft tissues in waterlogged, oxygen-poor burials, and revealing that the molecular signatures of peptide persistence closely mirror those of pathological protein stabilization in brain aging and neurodegeneration.
From Method-Defined Signals to Reference Measurement Procedures: Two Decades of Mass Spectrometry-Based ProGRP Quantification.
Coradduzza D, Azara E, La Salvia A … +4 more , Medici S, Carru C, Wood TD, Fanciulli G
J Proteome Res · 2026 Jul · PMID 42390060 · Publisher ↗
Pro-gastrin-releasing peptide (ProGRP) is a clinically established biomarker in small cell lung cancer (SCLC) and other neuroendocrine neoplasms (NENs). Despite widespread clinical use, ProGRP measurement is challenged b...
Pro-gastrin-releasing peptide (ProGRP) is a clinically established biomarker in small cell lung cancer (SCLC) and other neuroendocrine neoplasms (NENs). Despite widespread clinical use, ProGRP measurement is challenged by low circulating concentrations and proteoform heterogeneity arising from alternative precursor processing. Current immunoassay-based methods generate operationally defined signals anchored to antibody-epitope interactions rather than chemically explicit molecular quantities, limiting result comparability across platforms. Mass spectrometry (MS) addresses these limitations through sequence-defined quantification, with the capacity to resolve sequence-distinct isoforms and, at the intact-protein level, individual proteoforms. In this Perspective, we examine two decades of MS-based ProGRP quantification as a case study for quantitative proteomics and measurement science. We trace the evolution from single-quadrupole workflows to isotope dilution strategies enabling increasingly selective and metrologically robust measurement, showing that performance gains were driven primarily by selectivity engineering and internal standardization rather than by mass analyzer advances. This trajectory progressively exposes a fundamental comparability problem: immunoassays and MS-based methods do not measure the same quantities. Resolving this discordance requires an explicit metrological framework encompassing measurand definition, traceability architecture, and reference measurement procedures (RMPs) based on protein-level isotope dilution MS. ProGRP serves as an instructive model for harmonizing quantitative protein biomarker measurements in clinical proteomics.
Proteomic Profiling of Extracellular Vesicle-Enriched Plasma Using Mag-Net for Biomarker Discovery in Pancreatic Ductal Adenocarcinoma.
Buthelezi S, Elebo N, Naicker P … +13 more , Mokoena R, Dubazana S, Govender I, Mamputha S, Ellero A, Stoychev S, Mazibuko J, Ojo D, Candy G, Devar J, Cacciatore S, Omoshoro-Jones J, Nweke EE
J Proteome Res · 2026 Jun · PMID 42378051 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and was ranked among the top seven leading causes of cancer-related deaths in South Africa in 2020. Highlighting the urgent need for ongoing research...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and was ranked among the top seven leading causes of cancer-related deaths in South Africa in 2020. Highlighting the urgent need for ongoing research to identify reliable biomarkers to improve clinical outcomes. This study compared the plasma proteomes of patients with PDAC, those with benign biliary pathologies (BBP), and healthy controls (HC). We used Mag-Net, a magnetic-bead-based method that enriches membrane-bound vesicles. Comparative analyses identified distinct and overlapping dysregulated proteins between PDAC, BBP, and HC. PDAC showed enrichment for epithelial-mesenchymal transition, complement activation, hypoxia, glycolysis, and extracellular matrix remodeling pathways, consistent with aggressive tumor biology. Proteins including SPP1, THBS2, PTX3, FBLN2, SDC1, CTSS, and VCAN were significantly increased in PDAC, with LRG1 showing the strongest association with disease severity. Proteins, namely GPNMB, H4C1, SAA1, and CCDC47, demonstrated progressive upregulation across disease comparisons, suggesting potential relevance to disease progression. These findings demonstrate that plasma proteomics provides discriminatory molecular insights and supports the development of population-relevant biomarker panels. While several candidate proteins show promise for inclusion in multianalyte panels, further validation in larger cohorts is necessary to establish their diagnostic and translational utility for early detection, risk stratification, and improved differential diagnosis of PDAC.
Computationally Efficient Bayesian Estimation of Graphical Networks for Omics Data.
Adrian DW, VonKaenel ED, Obiri MY … +4 more , Degnan DJ, Sims AC, Oxford K, Bramer LM
J Proteome Res · 2026 Jun · PMID 42377400 · Publisher ↗
Graphical networks are useful, widely used modeling approaches to represent complex biological processes with biological measurements generated by platforms such as mass spectrometry. Bayesian analyses of graphical netwo...
Graphical networks are useful, widely used modeling approaches to represent complex biological processes with biological measurements generated by platforms such as mass spectrometry. Bayesian analyses of graphical networks for omics data have several advantages over their frequentist counterparts such as the inclusion of prior knowledge in the estimation of models. However, Bayesian approaches to date have only been feasible for data with a couple of hundred biomolecules due to prohibitive computational time, but omics data often contain tens of thousands of biomolecules. Here, we present and illustrate a more computationally efficient approach named BPlane (Bayesian PseudoLikelihood-based Algorithm for Network Estimation) to extend Bayesian modeling capabilities for larger-sized data sets, such as most untargeted proteomics data. Via simulation, we demonstrate that BPlane produces substantial computational savings over a current state-of-the-art Bayesian algorithm while maintaining competitive edge detection accuracy. We further demonstrate the computational benefit of BPlane on a SARS-CoV-2 proteomics data set with 7000 proteins.
Hierarchy of MS-Based Evidence.
Adams C, Leeming MG, Teschner D … +3 more , Hildebrandt A, Leidel SA, Palmblad M
J Proteome Res · 2026 Jun · PMID 42377072 · Publisher ↗
Scientific confidence relies on the integrity and verifiability of primary observations, yet increasing experimental scales and computational complexities challenge traditional mechanisms of trust. In proteomics, communi...
Scientific confidence relies on the integrity and verifiability of primary observations, yet increasing experimental scales and computational complexities challenge traditional mechanisms of trust. In proteomics, community standards emphasize the public deposition of raw mass spectrometry (MS) data to enable reanalysis and reproducibility. However, recent advances in software capable of simulating MS data raise the possibility that datasets may be altered or generated entirely and presented as experimentally acquired data. Here, we argue that current standards rarely distinguish between raw data formats in terms of their provenance guarantees or susceptibility to modification. To address this emerging vulnerability, we propose a hierarchy of evidence for MS-based reporting, analogous to established evidence hierarchies in medicine, in which confidence in reported findings increases with the traceability and verifiable provenance of raw data files. With this framework, we aim to support reviewers and readers in assessing the robustness of published claims and to stimulate discussion on strengthening data integrity safeguards in proteomics.
Proteomic Profiling of Exosomes from HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma: Selective Cargo Packaging.
Yadav J, Tripathi T, Tanwar N … +9 more , Sharma N, Chaudhary A, Janjua D, Joshi U, Aggarwal N, Chhokar A, Senrung A, Maras JS, Bharti AC
J Proteome Res · 2026 Jun · PMID 42372200 · Publisher ↗
Oncogenic viruses, such as human papillomavirus (HPV), alter the endosomal system to manipulate the proteomic content of extracellular vesicles, aiding their persistence and disease progression. HPV has emerged as a key...
Oncogenic viruses, such as human papillomavirus (HPV), alter the endosomal system to manipulate the proteomic content of extracellular vesicles, aiding their persistence and disease progression. HPV has emerged as a key risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of HPV on the exosomal proteomics remains poorly understood. Label-free quantitative proteomics was employed to analyze proteins extracted from HPV16-positive (93VU147T, UDSCC2) and HPV-negative (OCT1) HNSCC cell lines and their exosomes. Data are available via ProteomeXchange with identifier PXD067001. PCA revealed distinct clustering of HPV16-positive and -negative cells and exosomes. Differential expression analysis revealed 130 and 136 DEPs in exosomes of 93VU147T and UDSCC2, respectively, and 326 and 320 DEPs in the corresponding cells. Gene Ontology enrichment showed that HPV16-positive exosomal proteins and cells were associated mainly with protein digestion and absorption, different neurodegenerative diseases, and PI3K/Akt signaling. Exosomes showed distinct profiling from that of parental cells, emphasizing selective cargo packaging. Overall, the study demonstrates that HPV modulates the exosomal content in HNSCC, suggesting potential implications in tumor progression and biomarker discovery.
Proteomic Analysis Identifies ATE1-Dependent Arginylation Dysregulation across Meningioma Grades.
Macedo-da-Silva J, Pereira BJA, Mule SN … +4 more , Oba-Shinjo SM, Rosa-Fernandes L, Marie SKN, Palmisano G
J Proteome Res · 2026 Jun · PMID 42372081 · Publisher ↗
Meningiomas are the most common primary brain tumors, yet the molecular pathways that distinguish grade 1 from grade 2 lesions remain insufficiently understood. Among post-translational modifications, N-terminal arginyla...
Meningiomas are the most common primary brain tumors, yet the molecular pathways that distinguish grade 1 from grade 2 lesions remain insufficiently understood. Among post-translational modifications, N-terminal arginylation─catalyzed by ATE1─regulates protein stability and cellular stress responses, but its role in meningioma biology has not been explored. Here, we integrated mass-spectrometry-based proteomics, immunoblotting, and transcriptomic reanalysis to investigate pathway regulation across tumor grades. Grade 1 meningiomas displayed higher ATE1 expression and increased arginylation of key chaperones, accompanied by activation of the PERK branch of the unfolded protein response (UPR), enhanced autophagy, and greater engagement of apoptotics pathways. In contrast, grade 2 tumors showed reduced ATE1 levels, diminished BIP arginylation, attenuated UPR-PERK signaling, impaired autophagy, and increased proliferative signaling. Proteins predicted to be substrates of ATE1-mediated degradation were upregulated in grade 2 tumors, suggesting that loss of arginylation may stabilize pro-oncogenic factors. Together, these findings reveal grade-specific remodeling of the N-degron/arginylation axis and highlight protein arginylation as a previously unrecognized modulator of meningioma progression, with potential therapeutic relevance.
Proteomic Impact of Peripheral Expression of Mutant Huntingtin in .
Ezeigbo E, Stonebraker A, Yuliantoro H … +7 more , Adewoye A, Debastiani A, Roefer E, Biswas PK, Li P, Legleiter J, Valentine SJ
J Proteome Res · 2026 Jun · PMID 42371730 · Publisher ↗
Huntington's Disease (HD), a neurodegenerative disorder, is caused by the expansion of a polyglutamine (polyQ) tract near the N-terminus of the huntingtin protein (HTT), resulting in HTT aggregation. While associated wit...
Huntington's Disease (HD), a neurodegenerative disorder, is caused by the expansion of a polyglutamine (polyQ) tract near the N-terminus of the huntingtin protein (HTT), resulting in HTT aggregation. While associated with neurodegeneration, HTT is expressed ubiquitously throughout the body, leading to potential peripheral consequences of aggregation. However, the impact on peripheral tissues remains poorly understood in comparison to the central nervous system. Here, a () HD model that expresses an N-terminal HTT fragment (nonpathogenic 15Q or pathogenic 128Q) in body-wall muscle cells was used to evaluate proteome remodeling. Four conditions (15Q and 128Q on days 2 and 7 of adult worms, denoted as 15D2, 15D7, 128D2, and 128D7) were evaluated. In comparison to 15D2, 128D2 worms displayed decreased expression of ribosomal proteins and cytoskeletal components such as actin, profilin, calponin, and myosin, as well as overexpression of galectin, a stress- and inflammation-associated protein. By day 7, the 15D7 animals exhibited developmental signatures related to ribosome biogenesis, signal transduction, and vesicle trafficking, whereas abundance levels of proteins associated with stress response pathways such as proteostasis, protein folding, and cytoskeletal remodeling were observed to be increased in the 128D7 worms. These findings demonstrate the stage-dependent, nonlinear nature of HD-associated proteome disruption associated with peripheral expression of HD.
Phosphorylation Patterns of Preribosomal Proteins Associated with the RNA Exosome.
Almeida FA, Gomes Neto V, B Jantsch R … +7 more , Barros MRA, Cepeda LPP, Queiroz BRS, B Machado A, Menezes APJ, Da Cunha JPC, Oliveira CC
J Proteome Res · 2026 Jun · PMID 42370872 · Publisher ↗
The RNA exosome is an essential and ubiquitous RNase with exonucleolytic activity that is involved in ribosome biogenesis and RNA quality control in eukaryotes. It is present both in the nucleus and cytoplasm and interac...
The RNA exosome is an essential and ubiquitous RNase with exonucleolytic activity that is involved in ribosome biogenesis and RNA quality control in eukaryotes. It is present both in the nucleus and cytoplasm and interacts with specific cofactors in each cell compartment, which are essential for the recruitment and activity control of the exosome. Post-translational modifications are known to regulate enzyme activity and protein interaction, although their precise roles are individually specific. In this study, we investigated the phosphorylation status of proteins associated with the nuclear (Rrp6) and core (Rrp46) subunits of the RNA exosome in Using coimmunoprecipitation followed by phosphopeptide enrichment and high-resolution mass spectrometry, we identified 114 phosphorylation sites on proteins functionally related to rRNA processing. Differential phosphorylation patterns between Rrp6 and Rrp46 coimmunoprecipitations are consistent with distinct exosome assemblies and suggest potential regulatory roles for phosphorylation. Several phosphosites were identified in exosome subunits and cofactors, revealing potential regulatory mechanisms for fine-tuning exosome function. The results shown here highlight the role of phosphorylation in the recruitment and control of the exosome in RNA processing and degradation, offering new insights into the post-transcriptional control of gene expression.
Tissue Proteomic Signatures of -Mutated Colorectal Cancer Reveal New Insights into Aggressiveness, Immune Modulation, and Metabolic Reprogramming.
Miolo G, Marus W, Canil G … +3 more , Inversi A, Puglisi F, Corona G
J Proteome Res · 2026 Jun · PMID 42366749 · Publisher ↗
Colorectal cancer (CRC) is characterized by molecular heterogeneity, with -mutated tumors being particularly aggressive and refractory to standard therapies. This study aimed to identify distinctive proteomic signatures...
Colorectal cancer (CRC) is characterized by molecular heterogeneity, with -mutated tumors being particularly aggressive and refractory to standard therapies. This study aimed to identify distinctive proteomic signatures associated with the V600E mutation through comparative tumor tissue profiling. Thirty-three tumor tissues were analyzed: 9 -mutated, 14 -mutated, and 10 wild-type (WT). Proteomic profiling was performed on formalin-fixed, paraffin-embedded (FFPE) tissues using bottom-up LC-MS/MS in a data-independent acquisition mode. Protein identification and relative expression were achieved by using DIA-NN label-free analysis. Group differences were evaluated through multiparametric analyses, and Cox proportional hazard models were applied to identify proteins associated with overall survival. -mutated tumors showed distinct proteomic alterations, including overexpression of dipeptidyl peptidase 4 (DPP4) and lysophosphatidylcholine acyltransferase 1 (LPCAT1) alongside the downregulation of quinolinic phosphoribosyltransferase (QPRT) involved in NAD biosynthesis. Pathway analysis revealed the enrichment of protein folding associated with endoplasmic reticulum (ER) stress. Prognostic accuracy improved when tumor genotype was combined with the expression of activator of HSP90 ATPase activity 1 (AHSA1) and thioredoxin domain-containing 5 (TXNDC5), involved in ER-associated protein folding. These findings define a distinctive proteomic signature in -mutated CRC, characterized by dysregulated protein folding associated with ER stress and supporting the development of targeted therapies and more precise prognostic models.
Integrated Spatial and Bulk Untargeted Metabolomics Characterize Location- and Histology-Associated Metabolic Heterogeneity in Colorectal Cancer.
Wang J, Gao J, Liu J … +2 more , Hu D, Zhan Y
J Proteome Res · 2026 Jun · PMID 42366730 · Publisher ↗
Colorectal cancer (CRC) exhibits profound molecular heterogeneity according to primary tumor location, but spatially resolved assessment is limited by interindividual variability. Here, to minimize interindividual geneti...
Colorectal cancer (CRC) exhibits profound molecular heterogeneity according to primary tumor location, but spatially resolved assessment is limited by interindividual variability. Here, to minimize interindividual genetic confounding, we performed an exploratory single-case spatial metabolomics study (MALDI-MSI) on a rare case of synchronous bilateral tumors from one patient. This was complemented by untargeted metabolomics (UHPLC-HRMS/MS) on tumor and matched normal tissues from a cohort of 30 CRC patients with different anatomical sites and histologies. As an observational finding in this single case, the left-sided colon cancer (LCC) showed distinct metabolite distribution features from the tumor core to the invasive margin, whereas in right-sided colon cancer (RCC), metabolic differences were more closely associated with a histological subtype. UHPLC-HRMS/MS showed that, among tubular adenocarcinomas, LCC exhibited enrichments in ether lipid and phosphatidylcholine metabolism, whereas RCC preferred nucleotide and fatty acid metabolism. Furthermore, right-sided mucinous adenocarcinomas displayed unique sphingolipid alterations, consistent with a possible desaturase-associated shift from apoptosis-promoting pathways toward structural functions compared with the tubular subtype. Collectively, these findings underscore the potential influence of primary tumor location and histology on a microenvironmental metabolic architecture, offering exploratory insights for future hypothesis testing on location- and histology-dependent tumor adaptation.
Size-Resolved Lipoprotein Fatty Acid Content as a Novel Nuclear Magnetic Resonance-Derived Trait Specifically Associates with Genetic Variants That Control Fatty Acid Metabolism.
Belkadi A, Thareja G, Stephan N … +2 more , Halama A, Suhre K
J Proteome Res · 2026 Jun · PMID 42365607 · Publisher ↗
Population-level nuclear magnetic resonance (NMR)-based lipoprotein profiling is a key tool for investigating dysregulated lipoprotein metabolism and its role in cardiovascular disorders. However, associations with size-...
Population-level nuclear magnetic resonance (NMR)-based lipoprotein profiling is a key tool for investigating dysregulated lipoprotein metabolism and its role in cardiovascular disorders. However, associations with size-resolved lipoprotein composition readouts are difficult to dissect, as these traits are often highly correlated. Derived variables can therefore be more relevant to biological interpretation. Here, we show that the total fatty acid (FA) content of the lipoproteins derived from their lipid headgroup concentrations using the formula FA = 3TG + 2PL + CE strongly correlates (Spearman rho = 0.98) with the independently measured total fatty acid content. This observation is not self-evident since these variables are determined using different portions of the NMR spectrum. Using NMR data acquired on the Nightingale platform for 274,303 UK Biobank (UKB) participants and genetic associations as a readout, we then show that this relationship also holds at the size-resolved lipoprotein level. We identified eight gene loci where the proposed FA variables display a significantly stronger genetic association signal than that of the corresponding lipid headgroup variables. Five of these loci (LIPC, LIPG, PLB1, LPL, and APOC3) have a direct function in FA metabolism. Including computed size-resolved FA variables may therefore improve the biological interpretation of future studies based on Nightingale's data.
DigestedProteinDB: A Compact and Scalable Key-Value Database for In Silico Peptide Digestion and Mass-Based Search.
Cvrljak T, Diminic J, Zucko J … +3 more , Krizanovic K, Krsnik A, Starcevic A
J Proteome Res · 2026 Jun · PMID 42360919 · Publisher ↗
Efficient comparison of experimental peptide masses with theoretical values is a central step in mass spectrometry (MS)-based proteomics, microbial biotyping, and MS imaging. Such analyses increasingly require fast and s...
Efficient comparison of experimental peptide masses with theoretical values is a central step in mass spectrometry (MS)-based proteomics, microbial biotyping, and MS imaging. Such analyses increasingly require fast and scalable access to large collections of in silico-digested peptides derived from large-scale and continuously evolving protein-sequence databases. Here, we present DigestedProteinDB, a compact and high-performance key-value database of peptides generated by enzymatic in silico digestion of UniProtKB/Swiss-Prot and TrEMBL sequences. Implemented using RocksDB, the system incorporates multiple optimization layers, such as peptide mass discretization and multistage storage compression, to minimize disk footprint and accelerate mass-range queries. In benchmark tests using 252 million UniProtKB protein sequences (5.9 billion peptides, trypsin; 6-50 aa; two missed cleavages), DigestedProteinDB required approximately 250 GB of disk space and operated within 16 GB of system RAM. Database construction required ∼2 days, and end-to-end mass-range queries (±0.1 Da) achieved a median latency of ∼7 ms per query across a batch of 10,000 randomly sampled queries. The resulting database can be used as a standalone local resource or integrated into bioinformatics pipelines for peptide mass fingerprinting (PMF), MS/MS-based protein identification, and microbial biotyping. Due to its modular design, new databases can be generated rapidly for different proteases, taxonomic subsets, or digestion parameters.
Temperature Range Thermal Proteome Profiling for Drug Target Identification: A Practical Guide.
Xue Y, Chen P, Xing M … +2 more , Han L, Ying W
J Proteome Res · 2026 Jun · PMID 42360282 · Publisher ↗
Determining the drug targets and off-targets is crucial and can provide key information for the drug action mechanism. As one of the multiple methods used to identify the drug targets, thermal proteome profiling (TPP) is...
Determining the drug targets and off-targets is crucial and can provide key information for the drug action mechanism. As one of the multiple methods used to identify the drug targets, thermal proteome profiling (TPP) is more direct, simpler, and suitable for large-scale applications. TPP can also be used at the live-cell level to obtain more information about the pathway regulation beyond the direct targets. At present, there are three formats of TPP: temperature range TPP (TPP-TR), compound concentration range TPP (TPP-CCR), and two-dimensional TPP (2D-TPP). TPP-TR is the most widely practiced form and has been improved in different aspects. In this review, we systematically discuss the evolution, advantages, and limitations of TPP-TR sample preparation and data analysis to provide potential strategies for the development and application of innovative methods.
Proteomic Signatures of Vemurafenib Resistance in Canine Urothelial Carcinoma Harboring the BRAF Mutation.
Mohallem R, Dhawan D, Enstrom AW … +2 more , Knapp DW, Aryal UK
J Proteome Res · 2026 Jun · PMID 42359562 · Publisher ↗
Naturally occurring canine invasive urothelial carcinoma (InvUC) often harbors a BRAF mutation, analogous to human BRAF found across multiple cancer types, and has been used to investigate the effects of BRAF-targeted th...
Naturally occurring canine invasive urothelial carcinoma (InvUC) often harbors a BRAF mutation, analogous to human BRAF found across multiple cancer types, and has been used to investigate the effects of BRAF-targeted therapy. To investigate proteomic and phosphoproteomic changes during therapy, we analyzed 42 samples from 14 dogs with BRAF-positive InvUC treated with vemurafenib. Tumors were collected via cystoscopy before treatment (Pre-Vem), 1 month into treatment (Vem-1-month), and at the time of progressive disease (Vem-PD). We observed consistent early suppression of proteins and phosphosites in tumors after 1 month of vemurafenib treatment in dogs that responded to the treatment, followed by their rebound at the time of progressive disease, highlighting early tumor suppressive events that are later reversed as tumors adapt and develop resistance. Key pathways affected included "positive regulation of telomerase assembly and localization to Cajal body", "positive regulation of protein localization to telomere", and "positive regulation of protein localization to Cajal body". Additionally, consistent "Rho GTPase signaling" changes were observed across both proteomic and phosphoproteomic analyses, underscoring the functional reactivation of this pathway in resistant tumors. In summary, these findings reveal molecular signatures of early response and acquired resistance to vemurafenib and offer a valuable resource for future investigation of BRAF-targeted therapy.
Deciphering Allergen Peptides for Dermatological and Cosmetic Applications with Explainable Artificial Intelligence.
Damaso MG, Pimentel AS
J Proteome Res · 2026 Jun · PMID 42345568 · Publisher ↗
This study explores the potential of explainable artificial intelligence to advance our understanding of allergen peptides in the context of dermatology and cosmetics. We present a hybrid deep learning framework that int...
This study explores the potential of explainable artificial intelligence to advance our understanding of allergen peptides in the context of dermatology and cosmetics. We present a hybrid deep learning framework that integrates Temporal Convolutional Networks (TCN) and stacked Long Short-Term Memory (LSTM) architectures, enhanced with Evolutionary Scale Modeling (ESM) embeddings, to decode allergenic motifs embedded in peptide sequences. The ESM embeddings allow the model to capture both the evolutionary context and structural nuances of amino acids, enabling accurate classification of allergenic potential. Beyond classification, the framework emphasizes interpretability using state-of-the-art explainability tools such as Anchor, LIME, and SHAP. Anchor identifies minimal and decisive motifs responsible for allergenic activity, while LIME and SHAP provide a distributed importance map of , highlighting synergistic contributions across the peptide sequence. These methods ensure that the model output is not only precise, but it may also be biologically meaningful, opening a path to rational peptide modification strategies. In dermatology and cosmetic science, this approach represents a transformative tool, providing a scalable and transparent means to screen peptide-based formulations for allergenic risks, facilitates the design of safer bioactive peptides for therapeutic or cosmetic use, and supports regulatory compliance by grounding computational predictions in mechanistic explanations. Ultimately, the study bridges cutting-edge machine learning with dermatology and cosmetics, fostering the development of innovative, safe, and patient-centered cosmetic products.
Hypoxia Remodels the Extracellular Vesicle Proteome to Drive Metastasis in Breast Cancer via Metabolic-Epigenetic Coupling.
Bhavsar V, Sahu A, Karandikar A … +1 more , Taware R
J Proteome Res · 2026 Jul · PMID 42341239 · Publisher ↗
This study investigates how hypoxia remodels the extracellular vesicle (EV) proteome to promote metastasis in breast cancer (BC) cells. EVs from hypoxic MCF-7 and MDA-MB-231 cells were characterized and shown to enhance...
This study investigates how hypoxia remodels the extracellular vesicle (EV) proteome to promote metastasis in breast cancer (BC) cells. EVs from hypoxic MCF-7 and MDA-MB-231 cells were characterized and shown to enhance epithelial-mesenchymal transition (EMT), migration, invasion, and clonogenicity in recipient cells. Quantitative proteomics identified over 1250 EV proteins, with 78 commonly regulated by hypoxia across both cell lines. Pathway analysis revealed hypoxia-induced EV enrichment of ribosomal, chromatin remodeling, mitochondrial, and one-carbon metabolism proteins, alongside depletion of immune-modulatory factors. Interestingly, key one-carbon metabolism enzymes (SMS, CAD, and AHCYL1) were consistently upregulated in hypoxic EVs shed by both the cell lines. Notably, AHCYL1, a regulator of the methylation cycle enzyme AHCY, is significantly upregulated under hypoxic conditions. Our findings demonstrate that hypoxic EVs promote an increase in histone H3K9 trimethylation levels in recipient cells. This epigenetic shift downregulated epithelial and metastasis-suppressor genes (CDH1, EpCAM, and DKK1) while sustaining expression of EMT transcription factors (ZEB1 and SNAIL), thereby stabilizing EMT and enhancing invasiveness. Collectively, we describe a hypoxia-driven EV proteome that links metabolic reprogramming to epigenetic enforcement of metastatic traits in BC.
Novel Inflammatory Biomarkers for Poor Ovarian Response Detected by Follicular Fluid Olink Proteomics.
Guo L, Song J, Zou L … +7 more , Xia X, Gao T, Jiang J, Chen L, Sun Y, Yu C, Xue P
J Proteome Res · 2026 Jul · PMID 42341221 · Publisher ↗
Although inflammatory and immune mechanisms are known to play a crucial role in the pathogenesis of poor ovarian response (POR), their specific functions remain unclear. This study aimed to compare inflammatory proteins...
Although inflammatory and immune mechanisms are known to play a crucial role in the pathogenesis of poor ovarian response (POR), their specific functions remain unclear. This study aimed to compare inflammatory proteins in the follicular fluid of POR patients and those with normal ovarian reserve using Olink proteomics to identify differentially expressed proteins (DEPs) and their related pathways. Using the Olink Reveal platform, bioinformatics, and machine-learning models, we identified 50 DEPs. Correlation and protein-protein interaction analyses revealed relationships between key proteins, and SCG2 and TLR2 were screened as potential inflammatory biomarkers for POR. This study represents the first application of the Olink Reveal technology to profile the inflammatory proteome in the follicular fluid of women with POR, thereby providing critical insights into its pathophysiology and paving the way for novel strategies to improve the assisted reproductive outcomes.
Decreased Nonpolar Amino Acids in Cerebrospinal Fluid of Alzheimer's Disease Patients Revealed by Very High-Field NMR Spectroscopy.
Wuyart A, Martinez A, Oudart JB … +2 more , Mahmoudi R, Millot JM
J Proteome Res · 2026 Jul · PMID 42339780 · Publisher ↗
Alzheimer's disease (AD) is characterized by metabolic dysfunctions, making cerebrospinal fluid (CSF) an ideal biological matrix for characterizing brain metabolism. Very high-field 900 MHz nuclear magnetic resonance (NM...
Alzheimer's disease (AD) is characterized by metabolic dysfunctions, making cerebrospinal fluid (CSF) an ideal biological matrix for characterizing brain metabolism. Very high-field 900 MHz nuclear magnetic resonance (NMR) spectroscopy was used to profile CSF metabolites from 47 patients ( = 27 AD, = 20 non-AD). A total of forty-eight metabolites were identified and quantified. CSF concentrations of four nonpolar amino acids were reduced in AD: l-alanine ( = 0.001), l-valine ( = 0.02), l-leucine ( = 0.04), and l-phenylalanine ( = 0.04) (two-way ANOVA, pathology and sex as factors). No significant differences were observed for the other identified metabolites. A nonpolar amino acid factor (NAAF) was computed as the sum of these four metabolites ( < 0.001). Partial least-squares discriminant analysis (PLS-DA) based on the NAAF yielded moderate group separation (accuracy = 72%, = 0.22, = 0.006). Receiver operating characteristic (ROC) analysis demonstrated that the NAAF achieved the highest discriminatory performance over individual nonpolar amino acids (AUC = 0.83). l-Alanine correlated negatively with CSF tau markers (p-tau: = -0.40, = 0.005; t-tau: = -0.42, = 0.003); the NAAF displayed similar patterns (p-tau: = -0.38, = 0.009; t-tau: = -0.40, = 0.006). Very high-field NMR spectroscopy revealed a depletion of nonpolar amino acids in AD CSF, reflecting metabolic dysregulation in this neurodegenerative disease.
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