Proteomes最新文献

{"title":"Proteostasis, Assisted Reproductive Technologies, and Neurodevelopmental Differences: An Integrative Perspective.","authors":"Alberto Fucarino, Yousef Mohamadi, Francesco Cappello, Federica Scalia, Giulia Russo, Giuseppe Gullo, Leila Noori","doi":"10.3390/proteomes14020019","DOIUrl":"https://doi.org/10.3390/proteomes14020019","url":null,"abstract":"<p><p>Proteostasis, defined as the coordinated regulation of protein synthesis, folding, trafficking, and degradation, is essential for maintaining cellular integrity and supporting normal development. During reproduction and early life stages, efficient proteostasis is crucial for gamete quality, successful fertilization, embryonic development, and neurodevelopmental outcomes. Increasing evidence suggests that impaired proteostasis contributes to infertility and may be intertwined with biological vulnerabilities associated with assisted reproductive technologies [ARTs]. This review provides an integrative perspective on the role of disrupted proteostasis in infertility, ART procedures, and neurodevelopmental differences [NDD]. We review epidemiological and molecular findings indicating proteostasis failure in both male and female infertility, with particular emphasis on molecular chaperones. Among these, heat shock protein 60 [Hsp60] is discussed as a central mediator linking mitochondrial function, protein quality control, and reproductive competence. We further highlight that ART procedures coincide with sensitive periods of epigenetic reprogramming and proteostasis regulation during early embryogenesis, indicating that disturbances in proteostasis may affect epigenetic stability and subsequent neurodevelopmental outcomes. In addition, this review emphasizes the importance of proteoforms and proteome complexity as critical determinants of reproductive success and neurodevelopmental robustness in the context of ART. Finally, we discuss the potential of proteomic and chaperone-based biomarkers as emerging tools to optimize ART strategies, improve gamete and embryo selection, and enhance risk assessment and clinical outcomes. The current review underscores proteostasis as a fundamental yet underrecognized mechanism linking reproductive biology, ART outcomes, and long-term neurodevelopment while highlighting future directions for translational investigations.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enabling Next-Generation Mass Spectrometry-Based Proteomics: Standards, Proteoform Resolution, and FAIR, Reproducible, and Quantitative Analysis.","authors":"Rui Vitorino","doi":"10.3390/proteomes14020020","DOIUrl":"https://doi.org/10.3390/proteomes14020020","url":null,"abstract":"<p><p>Recent advances in mass spectrometry, data-independent acquisition, proteoform-resolving workflows, and multi-omics integration have significantly expanded the scale and scope of proteomics. However, the reuse and translational application of these datasets are limited by inconsistent standards, insufficient metadata, and inadequate computational interoperability. Proteoform-centric approaches provide higher molecular resolution by capturing intact protein variants and patterns of post-translational modification. Computational methods, including selected applications of machine learning and large language models (LLMs), are increasingly used for tasks such as spectral prediction and pattern discovery in clinical proteomics datasets. Despite these advancements, FAIR (Findable, Accessible, Interoperable, and Reusable) data practices, proteoform biology, and AI analytics are often pursued independently. This work presents an integrated framework for next-generation proteomics in which standardization and FAIR (Findable, Accessible, Interoperable, and Reusable) principles establish machine-actionable foundations for proteoform-resolved analysis and computational inference. It examines community efforts to promote data sharing and interoperability, as well as strategies for characterizing proteoforms using bottom-up, middle-down, and top-down approaches. It also highlights emerging AI and ML applications within the proteomics workflow. The framework emphasizes the importance of treating proteoforms as primary computational entities and adopting FAIR practices during data collection to enable reproducible and interpretable modeling. Finally, it introduces an architectural model that integrates FAIR infrastructures and proteoform resolution. In addition, practical recommendations for making AI-ready proteomics, including a minimal community checklist to support reproducibility, benchmarking, and translational scalability, are provided.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Banu et al. The Proteome of <i>Dictyostelium discoideum</i> Across Its Entire Life Cycle Reveals Sharp Transitions Between Developmental Stages. <i>Proteomes</i> 2026, <i>14</i>, 3.","authors":"Sarena Banu, P V Anusha, Pedro Beltran-Alvarez, Mohammed M Idris, Katharina C Wollenberg Valero, Francisco Rivero","doi":"10.3390/proteomes14020018","DOIUrl":"https://doi.org/10.3390/proteomes14020018","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Phosphosite-Specific Network Analysis of YES1 Y426 Reveals Cancer-Associated Phosphorylation Patterns.","authors":"Afreen Khanum, Leona Dcunha, Suhail Subair, Athira Perunelly Gopalakrishnan, Akhina Palollathil, Rajesh Raju","doi":"10.3390/proteomes14020017","DOIUrl":"https://doi.org/10.3390/proteomes14020017","url":null,"abstract":"<p><strong>Background: </strong>YES1 is an Src family non-receptor tyrosine-protein kinase that regulates cell growth, migration, survival, and oncogenic signaling. Although YES1 activation mechanisms and substrates have been extensively studied, its phosphosite-specific regulation across diverse biological contexts remains poorly understood.</p><p><strong>Methods: </strong>We performed a large-scale integrative analysis of 3825 publicly available human mass spectrometry-based phosphoproteomic datasets to map YES1 phosphorylation events. Co-modulation, co-occurrence, evolutionary conservation, and disease-association analyses were conducted to characterize the functional and clinical relevance of site-specific YES1 phosphorylation.</p><p><strong>Results: </strong>Y426 emerged as the predominant YES1 phosphosite across diverse biological conditions, localized within the activation loop of the kinase domain and conserved across Src family kinases. Co-modulation analysis identified 421 positively and 102 negatively associated phosphosites enriched in biological processes related to cell cycle regulation, transcription, cytoskeletal remodeling, apoptosis, and carcinogenesis. Among these high-confidence protein phosphosites, we identified 24 binary interactors, 5 upstream regulators, and 8 candidate downstream substrates. Comparison with DisGeNet cancer biomarkers showed overlap between YES1-associated phosphoproteomic signatures and site-specific oncogenic markers across multiple cancers, such as breast cancer, colorectal cancer, leukemia, and lung adenocarcinoma.</p><p><strong>Conclusions: </strong>This study provides a systems-level, phosphosite-focused view of YES1 signaling and supports a central regulatory role for Y426 within global phosphoregulatory and cancer-associated networks.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Reanalysis: Critical Issues in Data Reuse for Solid Tumor Proteomics.","authors":"Federica Franzetti, Nicole Giugni, Manuel Airoldi, Heather Bondi, Tiziana Alberio, Mauro Fasano","doi":"10.3390/proteomes14020016","DOIUrl":"https://doi.org/10.3390/proteomes14020016","url":null,"abstract":"<p><p>Proteomics represents a fundamental layer for understanding the molecular complexity of solid tumors by quantifying protein abundance and capturing proteoforms and post-translational modifications undetected in genomics or transcriptomics analyses. As mass spectrometry-based technologies and public proteomics repositories have expanded, opportunities for large-scale data reuse have grown accordingly. Nevertheless, data availability has not been translated into straightforward reuse: differences in experimental design, acquisition strategies, quantification workflows and metadata quality still limit the reproducibility and cross-study comparability. In this review, proteomics data reuse is defined as the systematic reanalysis and integration of publicly available datasets to support precision oncology applications such as biomarker assessment and antibody-drug conjugate target prioritization. We discuss reuse as an end-to-end analytical process, focusing on data analysis workflows, harmonization strategies, and the impact of heterogeneous experimental and analytical choices on interoperability. The increased application of artificial intelligence in proteomics data integration and reuse is also addressed, highlighting its analytical potential while underscoring the risks of overinterpretation when biological context and data structure are not adequately considered. Using colorectal and prostate cancer as representative examples, we illustrate how proteomics data reuse can support biological discovery and translational research, while critically examining the factors that limit robustness and clinical relevance.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Insights into the Immune and Sex-Specific Proteins in the Skin Mucus of Barramundi (<i>Lates calcarifer</i>).","authors":"Varsha V Balu, Dean R Jerry, Andreas L Lopata","doi":"10.3390/proteomes14010015","DOIUrl":"10.3390/proteomes14010015","url":null,"abstract":"<p><strong>Background: </strong>Fish skin mucus contains proteins involved in diverse biological pathways, representing a valuable non-invasive diagnostic of fish health.</p><p><strong>Methods: </strong>Skin mucus from three male and three female barramundi was analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) following protein extraction and S-Trap digestion.</p><p><strong>Results and discussion: </strong>A total of 1801 protein groups were matched to the <i>L. calcarifer</i> reference proteome and functionally annotated using Gene Ontology (GO) terms via UniProt ID mapping, with representation across Biological Process, Cellular Component, and Molecular Function categories. Functional classification using eggNOG-mapper further associated leading protein group sequences with Clusters of Orthologous Groups (COGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways. GO-based screening prioritised 352 putatively immune-relevant protein groups and 24 protein groups associated with sex- and reproduction-related processes, highlighting the functional complexity of the skin mucus proteome. Comparative analysis revealed sex-associated patterns in protein group detection and relative abundance, with differential abundance analysis identifying 244 protein groups exhibiting statistically significant differences between male and female samples.</p><p><strong>Conclusions: </strong>This study provides the first comprehensive discovery-based characterisation of the barramundi skin mucus proteome and establishes a baseline reference dataset for this aquaculture-relevant species. The findings support the utility of skin mucus proteomics for exploring immune and sex-associated molecular patterns and provide a baseline dataset for future validation studies investigating non-invasive health and reproductive monitoring.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of Catalytic Activity in VRK3: Phosphoproteomic Insights into the Regulatory Network of a Former Pseudokinase.","authors":"Ayadathil Sujina, Amal Fahma, Suhail Subair, Rajesh Raju, Poornima Ramesh","doi":"10.3390/proteomes14010014","DOIUrl":"10.3390/proteomes14010014","url":null,"abstract":"<p><p>Vaccinia-Related Kinase 3 (VRK3) is increasingly recognized as a crucial signaling modulator in both normal and pathological processes. This kinase was long thought of as a catalytically inactive pseudokinase, until recently it was established to phosphorylate Barrier to Autointegration Factor (BAF) proteins through its extracatalytic domain. VRK3 regulates diverse cellular pathways through scaffold interactions and context-dependent phosphorylation. This review is centered around the phosphoregulatory network that modulates VRK3 phosphorylation with implications in its abundance and function. A large-scale phosphoproteomic data integration was performed by combining phosphoproteomics profiling and differential phosphorylation from 115 mass spectrometry studies, identifying 32 high-confidence phosphorylation sites on VRK3. Notably, VRK3 (S59), (S82), and (S83) were predominantly observed highlighting plausible functional significance. These phosphorylation sites share 33 potential upstream kinases, and multiple interactor proteins, which in combination are known to regulate ERK, Hippo, and GPCR pathways. These insights advance the understanding of phosphorylation control by kinases and highlight opportunities to target VRK3-associated networks for therapeutic intervention in diseases such as glioma and liver cancer.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimethyl Sulfoxide Enhances HLA Peptide Identification.","authors":"Terry C C Lim Kam Sian, Yue Ding, Scott A Blundell, Ralf B Schittenhelm, Pouya Faridi","doi":"10.3390/proteomes14010013","DOIUrl":"10.3390/proteomes14010013","url":null,"abstract":"<p><p><b>Background:</b> Mass spectrometry (MS)-based immunopeptidomics has emerged as the gold standard for profiling HLA-bound peptides, yet detection remains challenging due to their non-tryptic nature, variable lengths, and lack of basic residues, which limit ionisation and fragmentation efficiency. <b>Methods:</b> To address these limitations, we investigated the impact of incorporating 5% dimethyl sulfoxide (DMSO) into LC-MS/MS mobile-phase buffers on immunopeptidomic workflows. Using B-lymphoblastoid cell lines expressing HLA class I and II alleles and elastase-digested HeLa lysates as a surrogate for non-tryptic peptides, we assessed peptide identification, ionisation efficiency, charge state distribution, and fragmentation quality. <b>Results:</b> DMSO significantly increased peptide identifications across all sample types, with gains of ~1.33 folds for HLA class I, ~1.55 folds for HLA class II, and ~1.24 folds for elastase digests. Improvements were systematic and reproducible, driven by enhanced electrospray ionisation, higher charge states, and superior MS2 spectral quality, evidenced by ~2-fold increase in b- and y-ion intensities. Importantly, DMSO did not introduce major sequence bias, preserving motif integrity and predicted binding characteristics. <b>Conclusions:</b> Overall, these findings establish DMSO as a robust additive for improving sensitivity and reliability in immunopeptidomics, particularly for low-input or clinically derived samples.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis in Search of New Biomarkers of Immune Thrombocytopenia (ITP)-A Review of Current Data.","authors":"Anastasia Boura-Theodorou, Konstantina Psatha, Stefania Maniatsi, Areti Kourti, Georgia Kaiafa, Michalis Aivaliotis, Kali Makedou","doi":"10.3390/proteomes14010012","DOIUrl":"10.3390/proteomes14010012","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is a hematological disorder commonly found in individuals of any gender, race, or age. Patients with ITP will present with thrombocytopenia either in a primary form or because of an infection or a dysfunction in the immune system. The severity of ITP is linked to diminished production of platelets due to the blockage of production in the bone marrow niche and increased destruction of platelets, which confirms the diagnosis of the disorder. The investigation of the pathogenesis of ITP is of critical importance as it can give an important indication of the state of the patient, guiding us through risk assessment and treatment. Proteomics can provide tools to explore the protein profile of ITP. In this review, we aimed to uncover different biomarkers, both diagnostic and prognostic, that have been investigated with proteomic methodologies and that might help in understanding the pathogenesis of ITP and providing personalized treatment to patients. Several differentially abundant proteins were identified, including haptoglobin isoforms, heat shock proteins (HSPA6, HSPA8), integrin β3 (ITGB3), 14-3-3 protein eta (YWHAH), vitamin D-binding protein, fibrinogen chains, MYH9, and FETUB, which are involved in key signaling pathways, such as PI3K/akt, TNF-a, and mTOR, and they demonstrate potential as diagnostic and prognostic biomarkers. Collectively, current data support the value of proteomics for uncovering the molecular landscape of ITP and guiding the development of precision diagnostics and personalized therapeutic strategies.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Responses of Maize Roots to Long-Term Cadmium Exposure: Adjustments of Class III Peroxidases, Plasma Membrane and Tonoplast Sub-Proteomes.","authors":"Sabine Lüthje, Ayse Gül Yilmaz, Kalaivani Ramanathan, Waldemar Gräfenstein, Jenny M Tabbert, Stefanie Wienkoop, Katrin Heino, François Clement Perrineau, Sönke Harder","doi":"10.3390/proteomes14010011","DOIUrl":"10.3390/proteomes14010011","url":null,"abstract":"<p><strong>Background: </strong>Crop plants have to deal with long-term cadmium exposure to farmlands contaminated by intensive use of fertilizers and pesticides. For uptake and sequestration, Cd²⁺ has to pass the plasma membrane and tonoplast. Class III peroxidases, plasma membrane, and tonoplast sub-proteomes were studied.</p><p><strong>Methods: </strong>Control and Cd²⁺-treated maize (<i>Zea mays</i> L.) were grown in hydroponics for 18 days. Soluble peroxidases were partially purified by chromatofocusing and characterized by substrate specificity. Membrane-bound peroxidases were analyzed spectrophotometrically and by non-reducing SDS-PAGE. Soluble and plasma membrane-bound peroxidases were identified by mass spectrometry. Shotgun proteomics was used to identify membrane proteins of differential abundance.</p><p><strong>Results: </strong>Guaiacol peroxidase activities increased in soluble fractions of Cd²⁺ samples. A Cd²⁺-specific soluble peroxidase (<i>Zm</i>Prx101) was identified, and <i>Zm</i>Prx85 abundance increased significantly in the plasma membrane. Substrate specificity of peroxidases revealed a preference for ferulic acid and esculetin, which was confirmed by docking analyses. Primary active transporters increased auxin efflux (brachytic2, ABCB9, and ABCB21), Cd²⁺ exclusion (ABCG34), and sequestration into the vacuole (HMA2, ABCB27). Evaluation of sub-proteome fractions demonstrated significant changes for proteins involved in disease resistance responses and cell wall modification.</p><p><strong>Conclusions: </strong>Molecular adjustments of maize root proteome to long-term Cd²⁺ exposure revealed relevance of low-abundant proteins for Cd²⁺ tolerance and putative stress markers.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}