ProteomicsPub Date : 2025-04-14DOI: 10.1002/pmic.202400241
Marilena M. Bourdakou, Eleni M. Loizidou, George M. Spyrou
{"title":"Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs","authors":"Marilena M. Bourdakou, Eleni M. Loizidou, George M. Spyrou","doi":"10.1002/pmic.202400241","DOIUrl":"10.1002/pmic.202400241","url":null,"abstract":"<p>Spaceflight poses unique challenges to human health due to exposure to increased levels of cosmic radiation, microgravity, and associated oxidative stress. These environmental factors can lead to cellular damage, inflammation, and a range of health complications, including cardiovascular problems, immune system impairment, and an increased risk of cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the body's defense mechanisms against oxidative stress by promoting the expression of antioxidant enzymes. Recent research has shed more light on the critical role of NRF2 in addressing space-related health challenges. In this study, we developed a computational methodology to explore the plasticity of the gene expression profile in flight and postflight conditions, highlighting the genes and corresponding mechanisms that do not return to ground levels and correlate with gene signatures associated with cardiovascular disease (CVD). RNA sequencing (RNA-seq) data from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used to investigate the cellular effects of microgravity on cardiac function. Gene expression monotonicity studies were performed and linked to genome-wide association studies (GWAS) to highlight the monotonically expressed genes associated with CVD. The selected monotonically expressed genes were also mapped onto the NRF2 network to investigate the impact of spaceflight on human cardiomyocyte function in the context of redox signaling pathways. Based on this knowledge, we used computational drug repurposing methods to suggest a short list of repurposed drug candidates that can be further tested in astronauts for the prevention of CVD. This study provides insights into the molecular and redox signaling alterations in cardiomyocytes induced by spaceflight, laying the foundation for future research aimed at mitigating cardiovascular risks in astronauts and advancing clinical applications on Earth.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 11-12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProteomicsPub Date : 2025-04-10DOI: 10.1002/pmic.202400398
Jesse Angelis, Eva Ayla Schröder, Zixuan Xiao, Wassim Gabriel, Mathias Wilhelm
{"title":"Peptide Property Prediction for Mass Spectrometry Using AI: An Introduction to State of the Art Models","authors":"Jesse Angelis, Eva Ayla Schröder, Zixuan Xiao, Wassim Gabriel, Mathias Wilhelm","doi":"10.1002/pmic.202400398","DOIUrl":"10.1002/pmic.202400398","url":null,"abstract":"<p>This review explores state of the art machine learning and deep learning models for peptide property prediction in mass spectrometry-based proteomics, including, but not limited to, models for predicting digestibility, retention time, charge state distribution, collisional cross section, fragmentation ion intensities, and detectability. The combination of these models enables not only the in silico generation of spectral libraries but also finds many additional use cases in the design of targeted assays or data-driven rescoring. This review serves as both an introduction for newcomers and an update for experienced researchers aiming to develop accessible and reproducible models for peptide property predictions. Key limitations of the current models, including difficulties in handling diverse post-translational modifications and instrument variability, highlight the need for large-scale, harmonized datasets, and standardized evaluation metrics for benchmarking.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 9-10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProteomicsPub Date : 2025-04-10DOI: 10.1002/pmic.202400354
Emily M. Martin, Federica Genovese, Harald Mischak, Justyna Siwy, Harald Rupprecht, Lorenzo Catanese, Agnieszka Latosinska
{"title":"Association of Urinary Collagen Type III Degradation Product With Kidney Function and Fibrosis in Chronic Kidney Disease Patients","authors":"Emily M. Martin, Federica Genovese, Harald Mischak, Justyna Siwy, Harald Rupprecht, Lorenzo Catanese, Agnieszka Latosinska","doi":"10.1002/pmic.202400354","DOIUrl":"10.1002/pmic.202400354","url":null,"abstract":"<p>A common hallmark of chronic kidney disease (CKD) is kidney fibrosis, which manifests as an increased deposition and turnover of collagens in the kidneys. Current clinical methods of monitoring disease progression in CKD patients do not truly reflect alterations at the tissue level without the use of invasive biopsies. Naturally occurring urinary peptides associated with kidney function and fibrosis have been previously identified using CE-MS as a non-invasive alternative. Moreover, a specific peptide from collagen type III, a highly abundant interstitial collagen, is the target for the C3M enzyme-linked immunosorbent assay (ELISA)-based assay and has been recorded in the CKD273 urinary biomarker panel measured by CE-MS. We aimed to investigate the intensities of the peptides incorporating the C3M sequence captured by CE-MS in urine of patients with CKD and analyze their association with estimated glomerular filtration rate (eGFR) and kidney interstitial fibrosis and tubular atrophy (IFTA). The investigated collagen type III peptides were reduced in abundance in urine of patients with CKD compared to healthy controls and the peptide intensities were independently correlated to eGFR and inversely correlated with IFTA score. Collectively, this analysis supports that peptides containing the C3M sequence are significantly associated with kidney function decline and tissue fibrosis.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 11-12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProteomicsPub Date : 2025-04-10DOI: 10.1002/pmic.202400187
Andrew T. Rajczewski, J. Alfredo Blakeley-Ruiz, Annaliese Meyer, Simina Vintila, Matthew R. McIlvin, Tim Van Den Bossche, Brian C. Searle, Timothy J. Griffin, Mak A. Saito, Manuel Kleiner, Pratik D. Jagtap
{"title":"Data-Independent Acquisition Mass Spectrometry as a Tool for Metaproteomics: Interlaboratory Comparison Using a Model Microbiome","authors":"Andrew T. Rajczewski, J. Alfredo Blakeley-Ruiz, Annaliese Meyer, Simina Vintila, Matthew R. McIlvin, Tim Van Den Bossche, Brian C. Searle, Timothy J. Griffin, Mak A. Saito, Manuel Kleiner, Pratik D. Jagtap","doi":"10.1002/pmic.202400187","DOIUrl":"10.1002/pmic.202400187","url":null,"abstract":"<p>Mass spectrometry (MS)-based metaproteomics is used to identify and quantify proteins in microbiome samples, with the frequently used methodology being data-dependent acquisition mass spectrometry (DDA-MS). However, DDA-MS is limited in its ability to reproducibly identify and quantify lower abundant peptides and proteins. To address DDA-MS deficiencies, proteomics researchers have started using Data-independent acquisition mass spectrometry (DIA-MS) for reproducible detection and quantification of peptides and proteins. We sought to evaluate the reproducibility and accuracy of DIA-MS metaproteomic measurements relative to DDA-MS using a mock community of known taxonomic composition. Artificial microbial communities of known composition were analyzed independently in three laboratories using DDA- and DIA-MS acquisition methods. In this study, DIA-MS yielded more protein and peptide identifications than DDA-MS in each laboratory for the particular instruments and software parameters chosen. In addition, the protein and peptide identifications were more reproducible in all laboratories and provided an accurate quantification of proteins and taxonomic groups in the samples. We also identified some limitations of current DIA tools when applied to metaproteomic data, highlighting specific needs to improve DIA tools enabling analysis of metaproteomic datasets from complex microbiomes. Ultimately, DIA-MS represents a promising strategy for MS-based metaproteomics due to its large number of detected proteins and peptides, reproducibility, deep sequencing capabilities, and accurate quantitation.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 9-10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProteomicsPub Date : 2025-04-10DOI: 10.1002/pmic.202400317
Luca Musella, Jens Möller, Christopher Lischer, Julio Vera-Gonzalez, Jörg Hofmann, Lisa Ott, Andreas Burkovski
{"title":"Proteome Analysis of Corynebacterium diphtheriae-Macrophage Interaction.","authors":"Luca Musella, Jens Möller, Christopher Lischer, Julio Vera-Gonzalez, Jörg Hofmann, Lisa Ott, Andreas Burkovski","doi":"10.1002/pmic.202400317","DOIUrl":"https://doi.org/10.1002/pmic.202400317","url":null,"abstract":"<p><p>Contact of Corynebacterium diphtheriae with macrophages induces adaptations on both bacterial and cellular sides. The study presented here was aiming to shed light on the simultaneous intracellular adaptation of the bacteria and changes in the proteome of the phagocytes in response to the internalization of C. diphtheriae. Quantitative proteome analyses were carried out at different time points of an infection assay and data were analyzed by different bioinformatic approaches. Several C. diphtheriae proteins, which were not observed or connected with pathogenicity before, were differentially expressed, as well as key macrophage components of the phagolysosome. Overall, bacteria responded to phagocytosis by changes in DNA repair, transcription, and cell wall synthesis proteins, while macrophages showed changes in components of the innate immune system.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e202400317"},"PeriodicalIF":3.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethics of Personalised Medicine: Importance of the Multidisciplinary Approach in KidneySign Project","authors":"Delphine Azéma, Flore Duranton, Àngel Argilés, Emmanuelle Rial-Sebbag","doi":"10.1002/pmic.202400176","DOIUrl":"10.1002/pmic.202400176","url":null,"abstract":"<p>This article explores the ethical and societal issues in developing personalised medicine (PM) as part of the KidneySign project, which aims to mobilise translational big data to validate a proteomic signature of renal fibrosis with prognostic value. This research offers hope for improved management of chronic kidney disease, including diagnosis and treatment. This article examines how the human and social sciences can be mobilised within a biomedical research project to identify and prevent concomitant ethical, legal and social issues. This point of view defends a multidisciplinary approach to PM and artificial intelligence in medicine. Presenting theoretical and methodological contributions of social sciences in the case of KidneySign offers an opportunity to better understand the integration of these disciplines in biomedical research. It allows us to question the study protocol itself and to frame it through legal obligations, as well as potential legal consequences and challenges. Moreover, sociological assessments help identify key points and highlight the limits of the technophilic fantasy in the representations of patients and health professionals. The introduction of new technologies into medical research and practice requires special attention to ethics.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 11-12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProteomicsPub Date : 2025-03-18DOI: 10.1002/pmic.202400238
Payman Nickchi, Uladzislau Vadadokhau, Mehdi Mirzaie, Marc Baumann, Amir A. Saei, Mohieddin Jafari
{"title":"Monitoring Functional Posttranslational Modifications Using a Data-Driven Proteome Informatic Pipeline","authors":"Payman Nickchi, Uladzislau Vadadokhau, Mehdi Mirzaie, Marc Baumann, Amir A. Saei, Mohieddin Jafari","doi":"10.1002/pmic.202400238","DOIUrl":"10.1002/pmic.202400238","url":null,"abstract":"<p>Posttranslational modifications (PTMs) are of significant interest in molecular biomedicine due to their crucial role in signal transduction across various cellular and organismal processes. Characterizing PTMs, distinguishing between functional and inert modifications, quantifying their occupancies, and understanding PTM crosstalk are challenging tasks in any biosystem. Studying each PTM often requires a specific, labor-intensive experimental design. Here, we present a PTM-centric proteome informatic pipeline for predicting relevant PTMs in mass spectrometry-based proteomics data without prior information. Once predicted, these in silico identified PTMs can be incorporated into a refined database search and compared to measured data. As a practical application, we demonstrate how this pipeline can be used to study glycoproteomics in oral squamous cell carcinoma based on the proteome profile of primary tumors. Subsequently, we experimentally identified cellular proteins that are differentially expressed in cells treated with multikinase inhibitors dasatinib and staurosporine using mass spectrometry-based proteomics. Computational enrichment analysis was then employed to determine the potential PTMs of differentially expressed proteins induced by both drugs. Finally, we conducted an additional round of database search with the predicted PTMs. Our pipeline successfully analyzed the enriched PTMs, and detected proteins not identified in the initial search. Our findings support the effectiveness of PTM-centric searching of MS data in proteomics based on computational enrichment analysis, and we propose integrating this approach into future proteomics search engines.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.202400238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}