Journal Of Proteomics[JOURNAL]
Sun
200 papers
Proteomic analysis of plasma-derived extracellular vesicles: Insights into acute stroke pathophysiology.
Reymond S, Gruaz L, Schvartz D … +3 more , Penalba A, Montaner J, Sanchez JC
J Proteomics · 2025 Aug · PMID 40451508 · Publisher ↗
Managing acute stroke is challenging and requires the differentiation of stroke subtypes while excluding stroke mimics. Understanding the biological processes underlying the different stroke subtypes could help improve a...
Managing acute stroke is challenging and requires the differentiation of stroke subtypes while excluding stroke mimics. Understanding the biological processes underlying the different stroke subtypes could help improve acute stroke care and patient outcomes. Plasma-derived extracellular vesicles (EVs) have emerged as promising tools for investigating these processes through their unique cargo. Therefore, we aimed at exploring the protein content of plasma-derived EVs in a cohort composed of patients with hemorrhagic stroke (n = 10), ischemic stroke with large-vessel occlusion (LVO) (n = 10) and without LVO (n = 10), transient ischemic attack (n = 10), stroke mimics (n = 10) and healthy controls (n = 10). EVs were isolated by size exclusion chromatography from 150 μL of plasma. Characterization was performed by transmission electron microscopy, western blotting and nanoparticle tracking analysis, and confirmed an efficient EV enrichment. Proteomics analysis was conducted using data-independent acquisition mass spectrometry and a supervised partial least squares discriminant analysis (PLS-DA) model was applied on proteomics data. The PLS-DA model successfully distinguished healthy controls, severe stroke subtypes (LVO ischemic and hemorrhagic stroke), and non LVO ischemic stroke, identifying key proteins influencing these patterns. These findings suggest that EVs and their protein cargo may play a role in critical processes like inflammation and coagulation in acute stroke pathology.
Differential gene expression networks and auxin responses during maize callus induction from explant tissues with contrasting embryogenic potential.
Juárez-González VT, Luján-Soto E, Aguirre de la Cruz PI … +4 more , Aquino-Luna M, Herrera-Díaz J, López-Ruiz BA, Dinkova TD
J Proteomics · 2025 Jun · PMID 40393645 · Publisher ↗
Maize somatic embryogenesis process depends on explant characteristics and genotype. The relationship between explant developmental timing and embryogenic potential of derived tissues is still poorly understood. The pres...
Maize somatic embryogenesis process depends on explant characteristics and genotype. The relationship between explant developmental timing and embryogenic potential of derived tissues is still poorly understood. The present work explored the adjustments of transcriptomes and proteomes from explants with contrasting embryogenic potential - immature and mature zygotic embryos from the Tuxpeño VS-535 genotype - during callus induction. Differentially accumulated transcripts and proteins were represented by oxidation/reduction, stress response, and metabolic process adjustments during the dedifferentiation of both explants. However, the explant with high embryogenic potential and derived callus displayed more significant enrichment in cell proliferation and plant hormone signal transduction pathways. Between the differentially accumulated proteins, it is of notice a significantly higher enrichment of catabolic and anoxia processes in non-embryogenic as opposed to anabolic and oxidation-reduction processes in the embryogenic callus induction. Transcription factors such as Auxin Response Factors (ARFs), signal transduction (Homeobox; HB), and embryogenesis-related AP2-EREB mRNAs characterized the immature embryos. Activator and repressor ARFs substantially differed at the early stages of callus induction between immature and mature embryo explants. The overall analysis of these findings helps to understand the molecular basis of gene expression regulation during callus dedifferentiation and auxin responses from maize explants with contrasting embryogenic potential. SIGNIFICANCE: This work contributes with overall transcript and protein patterns during the callus induction phase of Mexican landrace Tuxpeño VS-535 maize somatic embryogenesis from immature and mature embryos. Using comparisons between explants, between each explant and the induced callus, and between callus, differential biological process enrichment at transcript and protein levels for the embryogenic callus induction indicated key roles for cell proliferation, hormone signaling and biosynthetic processes for embryogenic callus induction. Furthermore, a battery of TF family enriched in the immature embryo, including several auxin response factors support the differential gene expression reprogramming during dedifferentiation from explants with contrasting embryogenic potential in maize somatic embryogenesis.
Comparative proteomics uncovers vital molecular players of central nervous system leukemia among Mexican pediatric patients.
Ruiz-May E, Bojórquez-Velázquez E, Carrasco-Vargas H … +11 more , Soto-Alvarez S, Rangel-Cova LS, Vargas-Hernández MA, Elizalde-Contreras JM, Torres De La Cruz VM, Vilchis-Ordoñez A, Palomo-Colli MÁ, Floriano TA, Ortega IP, Pelayo-Camacho R, Huerta-Nuñez LFE
J Proteomics · 2025 Jun · PMID 40389027 · Publisher ↗
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. The leukemic cells start in the bone marrow and spread to other vital organs and tissues, including the central nervous system (CNS)...
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. The leukemic cells start in the bone marrow and spread to other vital organs and tissues, including the central nervous system (CNS). Hispanic males are the community with the highest incidence of ALL. Unfortunately, there is limited information on the molecular signatures of leukemic cell infiltration into the CNS, which marks the progression from ALL to central nervous system leukemia (CNSL). To address this knowledge gap, we performed a label-free shotgun proteomics between the cerebrospinal fluid (CSF) from patients with ALL compared to those with confirmed CNSL. We were able to identify 619 proteins, including 340 proteins that had not been reported prevously in the CSF of subjects with CNSL. The major features associated with CNSL included the over-accumulation of cell-adhesion proteins such as L-selectin and several cadherin proteins, along with the modulation of enzymes associated with protein glycosylation, which may provide the appropriate conditions for leukemic cell infiltration into the CNS. The over-accumulation of proteins associated with ROS scavenging processes reveals hypoxic and redox homeostasis microenvironment conditions that favors ALL progression to CNSL. The further characterization of key differential proteins will be essential for establishing reliable molecular markers for CSNL. BIOLOGICAL SIGNIFICANCE: Central nervous system leukemia (CNSL) is a catastrophic progression of ALL defined by leukemic cells reaching the CNS. Limited comparative proteomics studies have been conducted previously between patients with ALL versus CNSL. While these studies were important pioneering steps, they were hindered by difficulties in obtaining the proper amount of protein samples related to CSF. They were based on minimal study subjects, and their proteomics pipelines did not include the depletion of high-abundance proteins. Defining the manners in which the CNSL proteome is perturbed compared to the ALL condition is paramount to understanding the molecular foundations of CNSL and identifying and characterizing protein markers for proper diagnosis. Improving the sensitivity and reliability of diagnosis using molecular markers would help clinicians to maximize patient outcomes and quality of life by implementing aggressive CNSL treatments as soon as possible in cases where infiltration has occurred, while avoiding exposure to toxic chemotherapies in patients where they are not yet necessary.
Protein digestion, peptide mass and peptide fragmentation with MZCal: A user-friendly phone-compatible application.
Willis B, Whitwell HJ
J Proteomics · 2025 Jun · PMID 40389026 · Publisher ↗
MZCal is a user-friendly, mobile-compatible web application designed for assisting peptide analysis in bottom-up mass spectrometry (MS). There are many tools for basic in-silico digestion, peptide mass and peptide mz cal...
MZCal is a user-friendly, mobile-compatible web application designed for assisting peptide analysis in bottom-up mass spectrometry (MS). There are many tools for basic in-silico digestion, peptide mass and peptide mz calculations, though not in a single, convenient and mobile-friendly format. Since internet availability can often be limited on mass-spectrometry linked computers, we developed MZCal for use in our laboratory, featuring tools that we commonly use in evaluating MS methods for bottom-up proteomics while working at the mass spectrometer. MZCal provides a single platform for in silico protein digestion, peptide mass and fragmentation calculations, and spectral prediction using MS2PIP. Optimised for use on both Android and iOS devices, MZCal enables convenient, real-time mass spectrum interpretation in laboratory settings and as a teaching resource. Unlike more complex web-tools, MZCal offers a streamlined interface that prioritises ease of use and accessibility. Overall, MZCal serves as a practical, portable solution for essential peptide calculations, providing an intuitive and accessible tool for both researchers and educators.
Fecal metaproteomics enables functional characterization of remission in patients with inflammatory bowel disease.
Wolf M, Lange J, Benndorf D … +14 more , Welz L, Nikolaus S, Siever LK, Tran F, Schallert K, Hellwig P, Schreiber S, Gunzer M, Rosenstiel P, Reichl U, Adolph T, Jukic A, Aden K, Heyer R
J Proteomics · 2025 Jun · PMID 40360052 · Publisher ↗
The gut microbiome is an important contributor to the development and the course of inflammatory bowel disease (IBD). While changes in the gut microbiome composition were observed in response to IBD therapy using biologi...
The gut microbiome is an important contributor to the development and the course of inflammatory bowel disease (IBD). While changes in the gut microbiome composition were observed in response to IBD therapy using biologics, studies elucidating human and microbial proteins and pathways in dependence on therapy success are sparse. Fecal samples of a cohort of IBD patients were collected before and after 14 weeks of treatment with three different biologics. Clinical disease activity scores were used to determine the clinical response and remission. Fecal metaproteomes of remitting patients (n = 12) and of non-remitting patients (n = 12) were compared before treatment and changes within both groups were assessed over sampling time to identify functional changes and potential human and microbial biomarkers. The abundance of proteins associated with neutrophilic granulocytes, and immunoglobulins significantly decreased in remitting patients. There were changes in pathways of microbial metabolism in samples from patients with remission after therapy, including an increased butyrate fermentation. Distinct changes of proteins related to gut inflammation and gut microbiome metabolism showed whether IBD remission was achieved or not. This suggests that metaproteomics could be a useful tool for monitoring remission in IBD therapies. SIGNIFICANCE: IBD is rising in incidence, especially in newly industrialized countries, and the microbiome is an important contributor to its pathogenesis. Despite manifold therapeutical options, achieving remission is often ineffective, and choosing new alternative drugs remains often empirical. Therefore, efficient tools for monitoring therapeutic response and assessing the effectiveness of drugs in specific patients are mandatory. In the present study, we show that the use of metaproteomics is a promising avenue to address these challenges. We observed the amelioration of inflammation and restoration of a healthy microbiome in remitting patients in contrast to non-remitting patients. Therefore, metaproteomics is a valuable tool for monitoring the therapy success in IBD.
Detection and identification of highly antigenic proteins from cytoskeleton of Toxoplasma gondii by immune-proteomics.
Lagunas-Cortés N, García-Sánchez BY, Ríos-Castro E … +6 more , Vega-López MA, González-Pozos S, Diaz-Martín RD, Carranza JM, Ramírez-Flores CJ, Mondragón-Flores R
J Proteomics · 2025 Jun · PMID 40339902 · Publisher ↗
Research on the immunogenic molecules of Toxoplasma is a key priority in the development of protective vaccines against the parasite. In the present study, we analyzed the profile of immunorecognized proteins from the To...
Research on the immunogenic molecules of Toxoplasma is a key priority in the development of protective vaccines against the parasite. In the present study, we analyzed the profile of immunorecognized proteins from the Toxoplasma cytoskeleton using sera from patients with both acute and chronic toxoplasmosis. The immunorecognized spots were analyzed by mass spectrometry and characterized by bioinformatic methods, leading to the identification of a total of 313 proteins. Sixty-three antigenic proteins were recognized by IgM antibodies and 250 antigenic proteins were recognized by IgG antibodies. About 10 proteins specifically reported as cytoskeletal proteins were identified with the IgG antibodies while 9 cytoskeletal proteins were detected by IgM antibodies. Bioinformatic analyses of the identified antigenic proteins were performed to determine their immunogenic potential, including the number of epitopes recognized by B lymphocytes, cytotoxic T lymphocytes (CD8+), and helper T lymphocytes (CD4+) receptors. This analysis enabled the selection of highly immunogenic proteins, which could serve as potential candidates for the design of a future vaccine against toxoplasmosis. SIGNIFICANCE: The study of immunogenic molecules from Toxoplasma gondii is a key priority in the search for protective vaccines. Despite partial success in previous strategies, identifying immunogenic proteins from the T. gondii cytoskeleton using immune-proteomics and bioinformatic approaches is crucial for vaccine development. This study provides valuable data that could serve as the foundation for designing novel immunogenic and immunoprotective molecules against toxoplasmosis.
Comparative secretome analysis of Oudemansiella raphanipes grown on different agricultural residues.
Zhu L, Ma S, Gao X … +4 more , Han J, Lu W, Yu H, Yang S
J Proteomics · 2025 Jun · PMID 40274096 · Publisher ↗
Oudemansiella raphanipes can degrade lignocellulose-rich biomass, especially agricultural residues. However, its substrate utilization and degradation mechanisms remain poorly understood. To explore this, we cultured O....
Oudemansiella raphanipes can degrade lignocellulose-rich biomass, especially agricultural residues. However, its substrate utilization and degradation mechanisms remain poorly understood. To explore this, we cultured O. raphanipes mycelium in Kirk's liquid medium supplemented with eight distinct substrates and conducted studies on extracellular enzyme activities and secretome analysis. A total of 905 secreted proteins were identified, with the cornstalk group having the highest counts. Carbohydrate-active enzymes (CAZymes) were the predominant type (32.8-48.9 %), followed by oxidoreductases (2.8 %-13.3 %), while lipase and phosphatase were minor categories. Functional annotation of the secreted proteins comprehensively revealed their diversity in various biological processes. Among the 340 secreted proteins with Enzyme Commission codes, (Methyl)glyoxal oxidase, chitinase, and β-glucosidase were most prominent. Bran, cottonseed hulls, corncobs, and the mixture promoted mycelium growth and conserved CAZymes expression patterns. In contrast, sawdust, corn steep liquor, and cornstalk induced divergent secretome profiles. Sawdust led to a higher proportion of hemicellulose- and lignin-degrading enzymes. Corn steep liquor induced relatively high activities and abundances of laccase and MnP, while cornstalk induced a broad spectrum of oxidoreductases, lipases, and protease & peptidases. In addition, redundancy analysis further indicated that the extracellular enzyme activities (notably laccase, MnP, and xylanase) induced by different substrates significantly impacted the secretome. SIGNIFICANCE: O. raphanipes can efficiently utilize a variety of lignocellulosic materials, and genomic sequencing has confirmed the presence of abundant CAZymes in its genome. This study employed various agricultural residues as substrate inducers to elucidate the extracellular enzyme profiles of O. raphanipes involved in lignocellulose degradation, which indicated its metabolic plasticity in response to varying substrate composition. These findings facilitate further exploration of the biomass bioconversion mechanism of O. raphanipes and provide novel perspectives for the induction of combined agro-residues in its industrial cultivation.
Resveratrol exerts antiviral activity against pseudorabies virus through regulation of the OPN-ERK/JNK-IL-1β signaling axis.
Luan H, Song Y, Hu H … +12 more , Zhang W, Zhang H, Su T, Wang J, Ye G, Yin Z, Zhao X, Zhou X, Li L, Zou Y, Zhang Y, Song X
J Proteomics · 2025 Jun · PMID 40274095 · Publisher ↗
Pseudorabies virus (PRV) can infect most mammals and has caused significant economic losses in global pig production. The emergence of new mutants significantly reduces the protective effect of vaccination, indicating an...
Pseudorabies virus (PRV) can infect most mammals and has caused significant economic losses in global pig production. The emergence of new mutants significantly reduces the protective effect of vaccination, indicating an urgent need for the development of specific therapeutic agents against PRV infection. In this study, we analyzed the changes in the cellular proteome after PRV infection in resveratrol-treated PK-15 cells using TMT quantitative proteomics combined with LC-MS/MS. The results identified the differential proteins osteopontin (iOPN) and interleukin-1 receptor accessory protein (IL-1RAP), which have significant biological implications. The regulation of OPN-IL-1β signaling by PRV infection was further studied through the OPN-ERK/JNK-IL-1β signaling axis. The transcriptional levels of OPN, C-JUN, IL-1RAP, and IL-1β, along with the protein levels of ERK, JNK, C-Jun, and their phosphorylated forms at 8, 12, and 16 h post-infection, were determined. The results showed that PRV infection inhibited the activation of this signaling axis, which was upregulated by resveratrol treatment. Down-regulation of OPN by siRNA increased PRV proliferation and inhibited the activation of the signaling axis, which was antagonized by resveratrol treatment. In PRV-infected mice, resveratrol treatment produced the same changes observed in vitro. The present study demonstrated that resveratrol can promote innate immune responses by regulating the OPN-ERK/JNK-IL-1β signaling axis, thereby activating host antiviral defenses against PRV infection. SIGNIFICANCE: Resveratrol targets the OPN-ERK/JNK-IL-1β axis to enhance innate immunity, offering a novel antiviral strategy against PRV infection. This study identifies OPN as a key regulator of host defense, linking ERK/JNK signaling to IL-1β-mediated antiviral responses. In vivo validation demonstrates resveratrol's therapeutic potential, reducing PRV replication and mortality in mice via immune pathway activation.
Ibaqpy: A scalable Python package for baseline quantification in proteomics leveraging SDRF metadata.
Zheng P, Audain E, Webel H … +6 more , Dai C, Klein J, Hitz MP, Sachsenberg T, Bai M, Perez-Riverol Y
J Proteomics · 2025 Jun · PMID 40268243 · Publisher ↗
Intensity-based absolute quantification (iBAQ) is essential in proteomics as it allows for the assessment of a protein's absolute abundance in various samples or conditions. However, the computation of these values for i...
Intensity-based absolute quantification (iBAQ) is essential in proteomics as it allows for the assessment of a protein's absolute abundance in various samples or conditions. However, the computation of these values for increasingly large-scale and high-throughput experiments, such as those using DIA, TMT, or LFQ workflows, poses significant challenges in scalability and reproducibility. Here, we present ibaqpy (https://github.com/bigbio/ibaqpy), a Python package designed to compute iBAQ values efficiently for experiments of any scale. Ibaqpy leverages the Sample and Data Relationship Format (SDRF) metadata standard to incorporate experimental metadata into the quantification workflow. This allows for automatic normalization and batch correction while accounting for key aspects of the experimental design, such as technical and biological replicates, fractionation strategies, and sample conditions. Designed for large-scale proteomics datasets, ibaqpy can also recompute iBAQ values for existing experiments when an SDRF is available. We showcased ibaqpy's capabilities by reanalyzing 17 public proteomics datasets from ProteomeXchange, covering HeLa cell lines with 4921 samples and 5766 MS runs, quantifying a total of 11,014 proteins. In our reanalysis, ibaqpy is a key component in automating reproducible quantification, reducing manual effort and making quantitative proteomics more accessible while supporting FAIR principles for data reuse. SIGNIFICANCE: Proteomics studies often rely on intensity-based absolute quantification (iBAQ) to assess protein abundance across various biological conditions. Despite its widespread use, computing iBAQ values at scale remains challenging due to the increasing complexity and volume of proteomics experiments. Existing tools frequently lack metadata integration, limiting their ability to handle experimental design intricacies such as replicates, fractions, and batch effects. Our work introduces ibaqpy, a scalable Python package that leverages the Sample and Data Relationship Format (SDRF) to compute iBAQ values efficiently while incorporating critical experimental metadata. By enabling automated normalization and batch correction, ibaqpy ensures reproducible and comparable quantification across large-scale datasets. We validated the utility of ibaqpy through the reanalysis of 17 public HeLa datasets, comprising over 200 million peptide features and quantifying 11,000 proteins across thousands of samples. This comprehensive reanalysis highlights the robustness and scalability of ibaqpy, making it an essential tool for researchers conducting large-scale proteomics experiments. Moreover, by promoting FAIR principles for data reuse and interoperability, ibaqpy offers a transformative approach to baseline protein quantification, supporting reproducible research and data integration within the proteomics community.
Comprehensive biobanking strategy with clinical impact at the European Cancer Moonshot Lund Center.
Oskolas H, Nogueira FCN, Domont GB … +33 more , Yu KH, Semenov YR, Sorger P, Steinfelder E, Corps L, Schulz L, Wieslander E, Fenyö D, Kárpáti S, Holló P, Kemény LV, Döme B, Megyesfalvi Z, Pawłowski K, Nishimura T, Kwon H, Encarnación-Guevara S, Szasz AM, Veréb Z, Gyulai R, Németh IB, Appelqvist R, Rezeli M, Baldetorp B, Horvatovich P, Malmström J, Pla I, Sanchez A, Knudsen B, Kiss A, Malm J, Marko-Varga G, Gil J
J Proteomics · 2025 May · PMID 40246065 · Publisher ↗
This white paper presents a comprehensive biobanking framework developed at the European Cancer Moonshot Lund Center that merges rigorous sample handling, advanced automation, and multi-omic analyses to accelerate precis...
This white paper presents a comprehensive biobanking framework developed at the European Cancer Moonshot Lund Center that merges rigorous sample handling, advanced automation, and multi-omic analyses to accelerate precision oncology. Tumor and blood-based workflows, supported by automated fractionation systems and standardized protocols, ensure the collection of high-quality biospecimens suitable for proteomic, genomic, and metabolic studies. A robust informatics infrastructure, integrating LIMS, barcoding, and REDCap, supports end-to-end traceability and realtime data synchronization, thereby enriching each sample with critical clinical metadata. Proteogenomic integration lies at the core of this initiative, uncovering tumor- and blood-based molecular profiles that inform cancer heterogeneity, metastasis, and therapeutic resistance. Machine learning and AI-driven models further enhance these datasets by stratifying patient populations, predicting therapeutic responses, and expediting the discovery of actionable targets and companion biomarkers. This synergy between technology, automation, and high-dimensional data analytics enables individualized treatment strategies in melanoma, lung, and other cancer types. Aligned with international programs such as the Cancer Moonshot and the ICPC, the Lund Center's approach fosters open collaboration and data sharing on a global scale. This scalable, patient-centric biobanking paradigm provides an adaptable model for institutions aiming to unify clinical, molecular, and computational resources for transformative cancer research.
Proteomics analysis of the mechanism of the treatment of corneal injury in dry-eye mice.
Zhang Z, Liu C, Wang J … +3 more , Liu Y, Li Y, Yao J
J Proteomics · 2025 May · PMID 40239947 · Publisher ↗
Dry eye disease (DED) is a common ocular surface disorder affecting millions globally. Clinical and experimental studies have shown that the traditional Chinese medicine formula Qingxuan Runmu Yin decoction (QXRMY) is ef...
Dry eye disease (DED) is a common ocular surface disorder affecting millions globally. Clinical and experimental studies have shown that the traditional Chinese medicine formula Qingxuan Runmu Yin decoction (QXRMY) is effective in treating DED. This study aimed to explore the molecular mechanisms of corneal damage in DED and evaluate QXRMY's therapeutic effects. A total of 120 C57BL/6 mice were divided into control, DED model, and QXRMY treatment groups. DIA sequencing of corneal tissue identified 2411 differentially expressed proteins. Enrichment analysis revealed these proteins were involved in RNA polymerase II regulation, apoptosis, and protein phosphorylation. KEGG pathway analysis highlighted key roles of the PI3K/AKT, HIF-1 signaling pathways, and cytoskeleton regulation in QXRMY's effects. FL, BUT, Schirmer I tests, HE, and PAS staining confirmed corneal damage in DED and the repair effects of QXRMY. ELISA showed QXRMY significantly reduced IL-1β, IL-6, and TNF-α levels, suggesting anti-inflammatory properties. PCR and Western blot further confirmed QXRMY repairs corneal damage via the PI3K/AKT/HIF1α pathway. This study provides new insights into the pathogenesis of DED and supports QXRMY's therapeutic potential in treating DED by alleviating inflammation and promoting corneal repair.
Integrative approaches for predicting protein network perturbations through machine learning and structural characterization.
Bengs BD, Nde J, Dutta S … +2 more , Li Y, Sardiu ME
J Proteomics · 2025 May · PMID 40228603 · Full text
Chromatin remodeling complexes, such as the Saccharomyces cerevisiae INO80 complex, exemplify how dynamic protein interaction networks govern cellular function through a balance of conserved structural modules and contex...
Chromatin remodeling complexes, such as the Saccharomyces cerevisiae INO80 complex, exemplify how dynamic protein interaction networks govern cellular function through a balance of conserved structural modules and context-dependent functional partnerships, as revealed by integrative machine learning and structural mapping approaches. In this study, we explored the INO80 complex using machine learning to predict network changes caused by genetic deletions. Tree-based models outperformed linear approaches, highlighting non-linear relationships within the interaction network. Feature selection identified key INO80 components (e.g., Arp5, Arp8) and cross-compartment features from other remodeling complexes like SWR1 and NuA4, emphasizing shared functional pathways. Perturbation patterns aligned with biological modules, particularly those linked to telomere maintenance and aging, underscoring the functional coherence of these networks. Structural mapping revealed that not all interactions are predictable through proximity alone, particularly with Arp5 and Yta7. By combining structural insights with machine learning, we enhanced predictions of genetic perturbation effects, providing a template for analyzing cross-species homologs (e.g., human INO80) and their disease-associated variants. This integrative approach bridges the gap between static structural data and dynamic functional networks, offering a pathway to disentangle conserved mechanisms from context-dependent adaptations in chromatin biology. SIGNIFICANCE: By leveraging an innovative, integrative machine learning approach, we have successfully predicted and analyzed perturbations in the INO80 network with good accuracy and depth. Our novel combination of machine learning, perturbation analysis, and structural investigation approach has provided crucial insights into the complex's structure-function relationships, shedding new light on its pivotal roles in affected pathways such as telomere maintenance. Our findings not only enhance our understanding of the INO80 complex but also establish a powerful framework for future studies in chromatin biology and beyond. This work represents a step forward in our understanding of chromatin remodeling complexes and their diverse cellular functions, laying the groundwork for future studies that can further refine our computational approaches and experimental techniques in this field.
Novel model organisms and proteomics for a better biological understanding.
Armengaud J, Cardon T, Cristobal S … +2 more , Matallana-Surget S, Bertile F
J Proteomics · 2025 May · PMID 40216077 · Publisher ↗
The concept of « model organisms » is being revisited in the light of the latest advances in multi-omics technologies that can now capture the full range of molecular events that occur over time, regardless of the organi...
The concept of « model organisms » is being revisited in the light of the latest advances in multi-omics technologies that can now capture the full range of molecular events that occur over time, regardless of the organism studied. Classic, well-studied models, such as Escherichia coli, Saccharomyces cerevisiae, to name a few, have long been valuable for hypothesis testing, reproducibility, and sharing common platforms among researchers. However, they are not suitable for all types of research. The complexity of unanswered questions in biology demands more elaborated systems, particularly to study plant and animal biodiversity, microbial ecosystems and their interactions with their hosts if any. More integrated systems, known as « holobionts », are emerging to describe and unify host organisms and associated microorganisms, providing an overview of all their possible interactions and trajectories. Comparative evolutionary proteomics offers interesting prospects for extrapolating knowledge from a few selected model organisms to others. This approach enables a deeper characterization of the diversity of proteins and proteoforms across the three branches of the tree of life, i.e. Bacteria, Archaea, and Eukarya. It also provides a powerful means to address remaining biological questions, such as identifying the key molecular players in organisms when they are confronted to environmental challenges, like anthropogenic toxicants, pathogens, dietary shifts or climate stressors, and proposing long-term sustainable solutions. SIGNIFICANCE: In this commentary, we reevaluated the concept of "model organisms" in light of advancements in multi-omics technologies. Traditional models have proven invaluable for hypothesis testing, reproducibility, and fostering shared research frameworks. However, we discussed that they are not universally applicable. To address complexities such as biodiversity and understand microbial ecosystems and their host interactions, integrated systems like "holobionts," which encompass host organisms and their associated microbes, are gaining prominence. Comparative evolutionary proteomics further enhances our understanding by enabling detailed exploration of protein diversity across organisms. This approach also facilitates the identification of critical molecular players in organisms facing environmental challenges, such as pollutants, pathogens, dietary changes, or climate stress, and contributes to developing sustainable long-term solutions.
Spatial and development responses in the wheat leaf highlight the loss of chloroplast protein homeostasis during salt stress.
Wijeweera S, Duncan O, Millar AH
J Proteomics · 2025 May · PMID 40189140 · Publisher ↗
Salinity stress in wheat affects physiological and biochemical parameters in tissues that alter plant development and ultimately lower crop yield. Shoot tissues can accumulate high concentrations of sodium over time thro...
Salinity stress in wheat affects physiological and biochemical parameters in tissues that alter plant development and ultimately lower crop yield. Shoot tissues can accumulate high concentrations of sodium over time through the transpiration stream coming from the roots. This imposes physiological responses that align salt effects with the basipetal developmental gradient of the monocot leaf. The role of metabolic processes in generating and responding to these increases in sodium concentration over time was explored by linking changes in ion distributions to those of enzyme abundance from the base to the tip of leaves under salt stress. We found that enzymes for methionine synthesis and lipid degradation pathways increase, concomitantly with proteins in jasmonate synthesis, which are key players in plant stress-induced responses. Combining the use of Differential Abundance of Protein analysis and Weighted Correlation Network Analysis we have focused on identifying key protein hubs associated with responses to salt stress or salt susceptibility, shedding light on potential sites of salt sensitivity as targets for enhancing salt tolerance in wheat. We found chloroplast protein synthesis machinery, including the 30S and 50S ribosomal proteins, and plastid localised protein synthesis elongation factors, were significantly reduced in abundance and correlated with the altered K/Na ratio along salt-stressed wheat leaves. Additionally, the plastid protease system including ATP-dependent caseinolytic protease and filamentous temperature-sensitive H proteases involved in chloroplast protein homeostasis, show decreased abundance with salt. The complex interplay of these processes in and across the leaf affects overall plant viability under salt stress mainly affecting the energy homeostasis in wheat shoot. Data are available via ProteomeXchange with identifier PXD059765. SIGNIFICANCE: Soil salinity is a major agricultural challenge that cause significant reduction in wheat yields, a staple crop vital for global food security. Despite extensive breeding efforts, developing salt-tolerant wheat remains challenging due to the complex, multi-genic nature of salinity tolerance. While numerous studies have explored molecular responses to salt stress making salt to control comparisons, there is little consensus on the primary points of metabolic disruptions that would determine the salt response in wheat. Our study addresses this gap by integrating proteomics with Weighted Correlation Network Analysis to examine metabolic responses along the developmental gradient of wheat leaves. By exploiting the natural base-to-tip progression of leaf maturation under salt stress, we identify key protein groups linked to salt response. These findings provide new insights into potential metabolic targets for enhancing wheat's resilience to salinity stress.
iTRAQ-based quantitative proteomics reveals dysregulation of fibronectin 1 contributes to impaired endometrial decidualization in recurrent implantation failure.
Wang J, Zhao X, Wu J … +4 more , Wang C, Wang Q, Fang Y, Yang X
J Proteomics · 2025 May · PMID 40187609 · Publisher ↗
Recurrent implantation failure (RIF) poses challenges to successful embryo implantation. In this study, we utilized isobaric tags for relative and absolute quantification (iTRAQ) to profile endometrial protein abundance...
Recurrent implantation failure (RIF) poses challenges to successful embryo implantation. In this study, we utilized isobaric tags for relative and absolute quantification (iTRAQ) to profile endometrial protein abundance in RIF patients. Through functional and pathway analyses, ECM-related proteins including fibronectin 1 (FN1), collagen type I alpha 2 chain (COL1A2), and integrin beta-1 (ITGB1) were revealed to be associated with RIF. Correlation analysis identified TGF-β1 as an upstream regulator of FN1. Knockdown experiments showed TGF-β1 downregulation could inhibit FN1 expression to inhibit decidualization markers. Our findings suggest a mechanistic link between TGF-β1/FN1 axis dysregulation and impaired decidualization observed in RIF. SIGNIFICANCE: Our study addresses the pressing issue of RIF, a significant obstacle in assisted reproductive technology. By employing isobaric tags for relative and absolute quantification (iTRAQ), we comprehensively analyzed endometrial protein abundance in RIF patients. Through functional and pathway enrichment analyses, we identified dysregulation in extracellular matrix (ECM)-related proteins, including FN1, COL1A2, and ITGB1, shedding light on their potential roles in implantation failure. Additionally, our correlation analysis revealed TGF-β1 as an upstream regulator of FN1, suggesting a novel regulatory axis involved in decidualization. Knockdown experiments further demonstrated the impact of TGF-β1 and FN1 on decidualization markers. This study contributes to a better understanding of the molecular mechanisms underlying RIF.
Advancing tissue analysis: Integrating mass tags with mass spectrometry imaging and immunohistochemistry.
Zhang D, Zhang H, Yang Y … +3 more , Jin Y, Chen Y, Wu C
J Proteomics · 2025 May · PMID 40180154 · Publisher ↗
In biological and biomedical research, it's a crucial task to detect or quantify proteins or proteomes accurately across multiple samples. Immunohistochemistry (IHC) and spatial proteomics based on mass spectrometry imag...
In biological and biomedical research, it's a crucial task to detect or quantify proteins or proteomes accurately across multiple samples. Immunohistochemistry (IHC) and spatial proteomics based on mass spectrometry imaging (MSI) are used to detect proteins in tissue samples. IHC can detect precisely but has a limited throughput, whereas MSI can simultaneously visualize thousands of specific chemical components but hindered by detailed protein annotation. Thereby, the introduction of mass tags may be adopted to expand the potential for integrating MSI and IHC. By enriching optical information for IHC and enhancing MS signals, mass tags can boost the accuracy of qualitative, localization, and quantitative detection of specific proteins in tissue sections, thereby widening the scope of protein detection and annotation results. Consequently, more comprehensive information regarding biological processes and disease states can be obtained, which aids in understanding complex biological processes and disease mechanisms and provides additional perspectives for clinical diagnosis and treatment. In the current review, we aim to discuss the role of different mass tags (e.g., mass tags based on inorganic molecules and organic molecules) in the combined application of MSI and IHC.
Proteomic insights into cell signaling and stress response mechanisms in Chaetoceros muelleri under nitrogen limitation.
de Jesús-Campos D, Bojórquez-Velázquez E, Ruiz-May E … +3 more , Fimbres-Olivarría D, Hayano-Kanashiro C, Huerta-Ocampo JÁ
J Proteomics · 2025 May · PMID 40122379 · Publisher ↗
Microalgae are often called "green factories" because they can perform photosynthesis, converting sunlight into biomass and high-value metabolites. Nitrogen concentration is a critical factor influencing protein accumula...
Microalgae are often called "green factories" because they can perform photosynthesis, converting sunlight into biomass and high-value metabolites. Nitrogen concentration is a critical factor influencing protein accumulation. Unfortunately, nitrogen deprivation often negatively impacts biomass production. Understanding the relationship between nitrogen concentration and protein accumulation is crucial for harnessing the potential of microalgae in various industries and addressing environmental challenges. Here, we quantitatively compared the proteomic profiles of Chaetoceros muelleri diatom, grown in two Nitrogen-deficient conditions and control treatment by employing a Tandem Mass Tag-based quantitative proteomic approach. Proteins involved in photosynthesis were differentially accumulated under moderately nitrogen-deficient conditions. In contrast, proteins involved in cell signaling and protection mechanisms were differentially accumulated under severely nitrogen-limited conditions. Proteins associated with nitrogen metabolism, carbohydrate metabolism, and protein biosynthesis were differentially decreased in severely nitrogen-limited conditions, indicating differential response mechanisms of C. muelleri to varying nitrogen conditions. Our results show that C. muelleri employs distinct strategies in response to nitrogen limitation. These results provide valuable insights into the adaptive strategies of C. muelleri under nitrogen limitation, offering potential applications in optimizing microalgal cultures for the enhanced production of target metabolites in industrial bioreactors. BIOLOGICAL SIGNIFICANCE: The marine diatom Chaetoceros muelleri accumulates lipids and carbohydrates under low nitrogen conditions without affecting its biomass. Response to nitrogen limitation in C. muelleri was examined by isobaric labelling-based proteomics. We identified changes mainly focused on photosynthesis pathways, cell signaling and protection mechanisms, nitrogen and carbohydrate metabolism, as well as protein biosynthesis. Our results indicate that C. muelleri activate unique strategies in response to different nitrogen concentrations, and this differential response represents a key factor for inducing metabolite accumulation without affecting biomass production.
Serum N-glycoproteomics characterization of differential N-glycosylation in schizophrenia.
Bi M, Chen Y, Tian Z
J Proteomics · 2025 May · PMID 40118250 · Publisher ↗
Glycosylation plays a crucial role in neurotransmission and signaling in schizophrenia; however, comprehensive characterization at the glycoproteome level is still lacking. Here we report our site- and structure-specific...
Glycosylation plays a crucial role in neurotransmission and signaling in schizophrenia; however, comprehensive characterization at the glycoproteome level is still lacking. Here we report our site- and structure-specific quantitative N-glycoproteomics characterization of differential N-glycosylation in the sera of schizophrenia patients at the molecular level of intact N-glycopeptide, where comprehensive qualitative (N-glycosite, monosaccharide composition and sequence structures of N-glycans) and quantitative (fold change) information are obtained. With tandem mass tag labeling, liquid chromatography tandem mass spectrometry analysis and site- and structure-specific DB search using GPSeeker, 7855 intact N-glycopeptides were identified corresponding to 1914 peptide backbones, 1997 N-glycosites and 1671 N-glycoprotein; where 1088 intact N-glycopeptides were differentially expressed in the sera of schizophrenia patients (relative to healthy control) with fold change of no less than 1.5. Function annotation of the corresponding N-glycoproteins was carried out. Neurodegeneration and complement pathway were enriched. These findings provide a comprehensive site- and structure-specific picture of aberrant N-glycosylation in schizophrenia and may foster further function and mechanism studies. SIGNIFICANCE: Schizophrenia, as a complex mental disorder, is affecting an increasing number of individuals globally, yet clinical research has struggled to clearly elucidate its pathogenesis. Current diagnostic and treatment approaches largely depend on patient symptoms and behavior, which lack precision. N-glycoproteomics offers a new dimension of understanding by exploring how schizophrenia alters protein glycosylation patterns in the body. Investigating N-glycoproteins not only contributes to the identification of novel early diagnostic biomarkers but also enhances our knowledge of disease pathogenesis. These molecular insights could pave the way for more accurate diagnostic tools and targeted therapies.
Proteomic insights into the molecular mechanism of anlotinib inhibition in TP53-mutated non-small cell lung cancer.
Jiang JM, Cheng ZW, Zhang L … +5 more , Tan TF, Zhang T, Shi HB, Hou KF, Xia Q
J Proteomics · 2025 May · PMID 40113013 · Publisher ↗
OBJECTIVE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. The aim of this...
OBJECTIVE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. The aim of this study was to investigate the inhibitory effect of anlotinib on TP53-mutated NSCLC and its possible mechanism. METHODS: The growth ability of TP53-mutated NSCLC cells were tested by Cell counting kit-8 assay. Proteins in TP53-mutated NSCLC cells treated with anlotinib were analyzed using label-free liquid chromatography-mass spectrometry. Differentially represented proteins were analyzed by KEGG, GO, and PPIs. TP53 pathway related proteins were verified using western blotting. RESULTS: The cell viability was significantly reduced in TP53-mutated NSCLC cell as opposed to TP53 wild cell by anlotinib treatment. 126 differentially represented proteins (37 upregulated and 89 downregulated) were found between the anlotinib and control groups in TP53-mutated NSCLC cell. Bioinformatics analyses revealed that the differentially represented proteins were primarily involved in catalytic activity, cellular processes, and metabolite interconversion. PANTHER Classification System found that anlotinib mainly impacted the p53 signaling pathway, De novo purine biosynthesis and Integrin signaling. KEGG enrichment and PPI networks of the differentially represented proteins revealed cyclin-dependent kinase 1 (CDK1) and mitogen-activated protein kinase kinase 3 (MAP2K3) as the core protein, which are related to the p53 signaling pathway. Western blotting also revealed that anlotinib significantly suppressed the expression of CDK1 and MAP2K3 in TP53-mutated NSCLC cells, that indicated the possible mechanism may involve the MAP2K3/p53/CDK1 pathway. CONCLUSIONS: Our findings showed that anlotinib selectively inhibited the growth of TP53-mutated NSCLC cells and downregulated the expression levels of CDK1 and MAP2K3. The MAP2K3/p53/CDK1 pathway may be the molecular mechanism underlying anlotinib's efficacy in TP53-mutated NSCLC. STATEMENT OF SIGNIFICANCE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. However, the action mechanism of anlotinib in the treatment of TP53-mutated NSCLC remains unclear. In this study, we used label-free quantitative proteomics to reveal the molecular mechanism of anlotinib inhibition in TP53-mutated NSCLC. We found that anlotinib significantly inhibited the growth of TP53-mutated NSCLC cells and downregulated the expression levels of CDK1 and MAP2K3. The MAP2K3/p53/CDK1 pathway may be the molecular mechanism underlying anlotinib's efficacy in TP53-mutated NSCLC. Our study promotes the use of anti-angiogenic drugs in TP53-mutated NSCLC. It provides new ideas for the treatment of TP53-mutated NSCLC.
Proteomics of Sternaspis chinensis to understand phosphate biomineralization in annelids.
Ge M, Mou A, Li X … +5 more , Hu X, Dong Y, Li Z, Zhang X, Xu Q
J Proteomics · 2025 May · PMID 40090575 · Publisher ↗
Organisms with phosphate hard tissues contribute to the evolutionary history of life and global biogeochemical cycles. The annelid Sternaspidae is an important group of phosphate-mineralizing organisms, known for its uni...
Organisms with phosphate hard tissues contribute to the evolutionary history of life and global biogeochemical cycles. The annelid Sternaspidae is an important group of phosphate-mineralizing organisms, known for its unique amorphous phosphate ventro-caudal shield. However, the molecular mechanisms underlying the formation of their phosphate shields remain unclear. In this study, we identified shield matrix proteins (ShiMPs) from Sternaspis chinensis (SC group with hard shield) and Sternaspis liui syn (SL group with soft shield) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1360 ShiMPs were identified, with 237 differentially expressed proteins between the two morphologies. The differential expression of collagen, extracellular matrix proteins with new EGF-VWA domains, and calcium-binding proteins in different morphological shields suggested that they may be associated with the variation in shield phenotypes. Furthermore, the phenoloxidase innate immune cascade pathway was found to be upregulated in the SL group. Compared with other biomineral proteins, sternaspid shields lacked typical chitin-related proteins but were rich in collagen proteins containing EGF domains, suggesting that collagen may serve as a scaffold for amorphous phosphate deposition. This study provided a molecular dataset for the formation of sternaspid shields and revealed the molecular regulatory features of different shield morphologies. SIGNIFICANCE: Phosphate is one of the important types of biominerals in invertebrates. However, the molecular mechanisms underlying its formation in these organisms remain poorly understood, and no studies have yet explored phosphate biomineralization in annelids. In this study, we performed proteomic analysis of matrix proteins in the phosphate shields of the annelid Sternaspidae to provide new insights into phosphate biomineralization in this group. Comparative analysis of the matrix proteins in different morphological shields from Sternaspis chinensis revealed the regulation of collagen, extracellular matrix proteins, calcium-binding proteins, and immune-related proteins. By comparing with other biominerals, we proposed that collagen may serve as a scaffold for amorphous phosphate deposition in sternaspid shields. This study advances our understanding of phosphate biomineralization in annelids and provides a foundation for future research on the formation mechanisms of phosphate biominerals in invertebrates.
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