{"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":"https://doi.org/10.1002/pmic.202400176","url":null,"abstract":"<p><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":" ","pages":"e202400176"},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1002/pmic.202400238","url":null,"abstract":"<p><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":" ","pages":"e202400238"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development and Validation of a Capillary Electrophoresis Coupled to Mass Spectrometry Pipeline for Comparable Assessment of the Plasma Peptidome.","authors":"Lucie Fernandez, Benjamin Breuil, Carine Froment, Mouhamed Seye, Babacar Sylla, Marina Estanco, Adeline Chaubet, Eléonore Delecroix, Karima Chaoui, Jeanne Pierrette Vu, Serban Ardeleanu, Stanislas Faguer, Odile Burlet-Schiltz, Bénédicte Buffin-Meyer, Joost P Schanstra, Julie Klein","doi":"10.1002/pmic.202400114","DOIUrl":"https://doi.org/10.1002/pmic.202400114","url":null,"abstract":"<p><p>Although capillary electrophoresis coupled to mass spectrometry (CE-MS) holds promise for urinary peptide profiling, only a limited number of studies have used CE-MS to study plasma peptides. Here we describe the establishment of a workflow, including sample preparation, CE-MS analysis, data processing and normalization optimized for the analysis of plasma peptides. Using 291 plasma samples from 136 patients with end stage kidney failure (including pre- and post-dialysis samples) and 20 patients with chronic kidney disease, we identified and quantified the abundance of 3920 unique plasma peptides. The repeatability and intermediate precision of the analysis were high (with a coefficient of variation of 5% on average for all peptides). Six hundred sixty-one out of 3920 peptides were sequenced by CE-MS/MS. These peptide fragments belonged to 135 parent proteins. Using the pipeline, we identified 169 sequenced plasma peptides with different plasma abundance pre- and post-dialysis. These peptides combined in a support vector machine (SVM) classifier successfully discriminated between pre- and post-dialysis samples in a blinded validation cohort of 45 dialysis patients. Enriched peptides post-dialyses were for the major part associated to inflammation and the coagulation contact systems that may serve as signatures for optimizing dialysis materials. In conclusion, this high-throughput strategy focuses on the plasma peptidome, an understudied component of the plasma, as a promising area for further exploration. Due to their close proximity to the vascular bed, plasma peptides hold significant potential to serve as reliable biomarkers for systemic complications associated with kidney disease.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e202400114"},"PeriodicalIF":3.4,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646724","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}
ProteomicsPub Date : 2025-03-12DOI: 10.1002/pmic.202400239
Vanessa Horn, Patricia Zarnovican, Birgit Tiemann, Andreas Pich, Hans Bakker, Françoise H Routier
{"title":"N-Glycoproteomics of the Apicomplexan Parasite Toxoplasma gondii.","authors":"Vanessa Horn, Patricia Zarnovican, Birgit Tiemann, Andreas Pich, Hans Bakker, Françoise H Routier","doi":"10.1002/pmic.202400239","DOIUrl":"https://doi.org/10.1002/pmic.202400239","url":null,"abstract":"<p><p>Protein N-glycosylation influences protein folding, stability, and trafficking, and has prominent functions in cell-cell adhesion and recognition. For the parasite Toxoplasma gondii, N-glycosylation of proteins is crucial for initial adhesion to host cells, parasite motility, and consequently, its ability to invade host cells. However, the glycoproteome of T. gondii remains largely unknown. In this study, we used the α-mannose-specific Burkholderia cenocepacia lectin A (BC2L-A) to enrich glycopeptides from T. gondii tachyzoites and analysed them by tandem mass spectrometry. The data enable the identification of over 100 N-glycoproteins with the glycosylation site(s) and the composition of the N-glycans at each site. T. gondii glycoproteins include known virulence factors, vaccine candidates as well as numerous uncharacterised proteins. These data provide ground knowledge to deepen our understanding of the role of glycoproteins in invasion and assist the rational design of vaccines.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e202400239"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603028","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}