Morgan Carlton, Tuo Zang, Tony J Parker, Chamindie Punyadeera, Joanne Voisey, Leila Cuttle
{"title":"Salivary Proteome Is Altered in Children With Small Area Thermal Burns.","authors":"Morgan Carlton, Tuo Zang, Tony J Parker, Chamindie Punyadeera, Joanne Voisey, Leila Cuttle","doi":"10.1002/prca.202300107","DOIUrl":"10.1002/prca.202300107","url":null,"abstract":"<p><p>Saliva is a child appropriate biofluid, but it has not previously been used to evaluate the systemic response to burn injury in children. The aim of this study was to investigate the salivary proteome of children with small area thermal skin burns relative to different burn characteristics (mechanism, time to re-epithelialization and risk of emotional distress). SWATH Mass Spectrometry was used to quantify the abundance of 742 proteins in the saliva of children with burns (n = 22) and healthy controls (n = 37). Eight proteins were differentially abundant in the saliva of children with burns compared to healthy children, and these were associated with immune processes, epidermal cell differentiation and transferrin receptor binding. Eleven proteins were differentially abundant in patients with burns of different mechanisms. Scald burns had an over-representation of immune/inflammatory response processes, and contact burns had an over-representation of cornification, intermediate filament assembly and cell death cellular processes. Four proteins were elevated in patients who were at high risk for emotional distress and 15 proteins were correlated with time to wound re-epithelialization. This pilot study proves that saliva can be used for paediatric biomarker discovery and can be used as a diagnostic and prognostic sample to investigate systemic changes in a paediatric burn cohort.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300107"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080750","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}
{"title":"Computational Insight in the Identification of Non-Synonymous Single-Nucleotide Polymorphism Affecting the Structure and Function of Interleukin-4.","authors":"Pratima Roy, Siddharth Sharma, Manoj Baranwal","doi":"10.1002/prca.202400070","DOIUrl":"10.1002/prca.202400070","url":null,"abstract":"<p><strong>Background: </strong>IL4 is a versatile cytokine essentially known for differentiation, proliferation and cell death in cells. Its dysregulation has been found to be associated with the development of inflammatory disorders.</p><p><strong>Objective: </strong>The goal of the current investigation is to identify and select non-synonymous single-nucleotide polymorphisms (nsSNPs) in the IL-4 gene by employing computational methods which may have a potential functional impact on the occurrence of disease.</p><p><strong>Method and result: </strong>Six different nsSNPs were predicted to be deleterious based on the consensus of different algorithms: SIFT, Polyphen2 (Humdiv and HumVar), PredictSNP and SNP&GO. I-mutant and MuPro assessment revealed a decrease in the stability of these mutants except K150M. Modelling was then carried out to build the wild type along with its mutants, followed by superimposition of the wild type with mutants to evaluate the RMSD value, which lies between 0.26 and 0.34. Simulation results of mutant models, along with wild type, showed that four of the mutants (N113Y, A118G, R109W and K150M) deviated most and were unstable. A118G showed a significant deviation from the wild type, while V53A and C123R were stable.</p><p><strong>Conclusion: </strong>The finding establishes the evidence that the identified six nsSNPs of IL-4 can be the new entrant presenting their candidature for genetic testing.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400070"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795054","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}
Estelle Maret, Kim Wiskott, Tobias Shipley, Federica Gilardi, Marc Augsburger, Aurelien Thomas, Tony Fracasso, Tatjana Sajic
{"title":"Activity-Based Proteome Profiling of Serum Serine Hydrolases: Application in Pediatric Abusive Head Trauma.","authors":"Estelle Maret, Kim Wiskott, Tobias Shipley, Federica Gilardi, Marc Augsburger, Aurelien Thomas, Tony Fracasso, Tatjana Sajic","doi":"10.1002/prca.202400022","DOIUrl":"10.1002/prca.202400022","url":null,"abstract":"<p><strong>Purpose: </strong>Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial hemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes.</p><p><strong>Experimental design: </strong>Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation, and neuronal signaling. Here, we investigated activity-based protein profiling (ABPP) coupled to liquid chromatography-mass spectrometry (LC-MS) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS).</p><p><strong>Results: </strong>Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism.</p><p><strong>Conclusions and clinical relevance: </strong>To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400022"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865203","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":"ECMHA-PP: A Breast Cancer Prognosis Prediction Model Based on Energy-Constrained Multi-Head Self-Attention.","authors":"Fan Zhang, Chaoyang Liu, Xinhong Zhang","doi":"10.1002/prca.202400035","DOIUrl":"10.1002/prca.202400035","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer is a significant threat to women's health. Precise prognosis prediction for breast cancer can help doctors implement more rational treatment strategies. Artificial intelligence can assist doctors in decision-making and enhance prediction accuracy.</p><p><strong>Experimental design: </strong>In this paper, a deep learning model ECMHA-PP (Energy Constrained Multi-Head Self-Attention based Prognosis Prediction) is proposed to predict the prognosis of breast cancer. ECMHA-PP utilizes patients' clinical data and extracts features through a cross-position mix and a channel mix multi-layer perceptron. Then, it incorporates an energy-constrained multi-head self-attention layer to improve feature extraction capability. The source code of ECMHA-PP has been hosted on GitHub and is available at https://github.com/xiaoliu166370/ECMHA-PP.</p><p><strong>Results: </strong>To evaluate our proposed method, prognostic prediction experiments were performed on the METABRIC dataset, yielding outstanding results with an average accuracy of 93.0% and an average area under the curve of 0.974. To further validate the model's performance, we conducted tests on another independent dataset, BRCA, achieving an accuracy of 87.6%.</p><p><strong>Conclusions and clinical relevance: </strong>In comparison with other widely used advanced methods, ECMHA-PP demonstrated higher comprehensive performance, making it a reliable prognostic prediction model for breast cancer. Given its robust feature extraction and prediction capabilities.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400035"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771714","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":"dRama: Differential Ramachandran Plot as a Tool to Analyze Subtle Changes in Protein Secondary Structure.","authors":"Piotr Batys, Leszek Krzemień, Jakub Barbasz","doi":"10.1002/prca.202400087","DOIUrl":"10.1002/prca.202400087","url":null,"abstract":"<p><p>Determination of the changes in protein structure is crucial for a better understanding of their function and properties, which is highly important in identifying the causes of the disease, new drug development, and clinical applications. The Ramachandran plot, displaying the set of torsional angles, phi (Φ) and psi (Ψ), of the protein backbone, serves as a popular and convenient tool for secondary structure analysis and interpretation. However, identifying subtle changes in protein structure is often hindered in traditional Ramachandran plot, especially with the large amount of data generated by molecular dynamics (MD) simulations. In this paper, we proposed a useful and efficient tool, that is, differential Ramachandran plot (dRama), which enables to compare protein structures and extract the differences, providing a highly readable graphical representation. dRama is available at: https://github.com/MaksWolf44/dRama.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400087"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710816","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":"Understanding LC/MS-Based Metabolomics: A Detailed Reference for Natural Product Analysis.","authors":"Jyotirmay Sarkar, Rajveer Singh, Shivani Chandel","doi":"10.1002/prca.202400048","DOIUrl":"10.1002/prca.202400048","url":null,"abstract":"<p><p>Liquid chromatography, when used in conjunction with mass spectrometry (LC/MS), is a powerful tool for conducting accurate and reproducible investigations of numerous metabolites in natural products (NPs). LC/MS has gained prominence in metabolomic research due to its high throughput, the availability of multiple ionization techniques and its ability to provide comprehensive metabolite coverage. This unique method can significantly influence various scientific domains. This review offers a comprehensive overview of the current state of LC/MS-based metabolomics in the investigation of NPs. This review provides a thorough overview of the state of the art in LC/MS-based metabolomics for the investigation of NPs. It covers the principles of LC/MS, various aspects of LC/MS-based metabolomics such as sample preparation, LC modes, method development, ionization techniques and data pre-processing. Moreover, it presents the applications of LC/MS-based metabolomics in numerous fields of NPs research such as including biomarker discovery, the agricultural research, food analysis, the study of marine NPs and microbiological research. Additionally, this review discusses the challenges and limitations of LC/MS-based metabolomics, as well as emerging trends and developments in this field.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400048"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546981","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":"Proteomic Analysis of Fibroblasts Exposed to Resin Composite Release.","authors":"Yohann Flottes, Elisabeth Dursun","doi":"10.1002/prca.202400049","DOIUrl":"10.1002/prca.202400049","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the potential effects of products released by a resin composite on the proteome of human gingival fibroblasts.</p><p><strong>Methods: </strong>Fifteen resin composite cylinders of a Bis-GMA-based resin composite (Tetric EvoCeram, Ivoclar) were made and placed in a culture medium for 24 h. Then, 30 mL of this medium was placed for 72 h in contact with human gingival fibroblasts and a second control group consisted of cells placed in culture medium only. Afterward, cells were collected, washed, and their proteins extracted. Three two-dimensional electrophoresis were performed per condition. Image analysis of the gels was carried out to highlight the differential protein spots. These spots were then analyzed by an ESI/qTOF mass spectrometer. Finally, specific databases provided protein identification, their interactions, and the pathways where they are implicated.</p><p><strong>Results: </strong>Delta2D software allowed the detection of 21 spots of different proteins. The MASCOT identified 28 proteins. Five proteins from four spots were upregulated, 23 proteins from 17 spots were downregulated. The UniProt database showed that all these proteins were involved in cellular architecture, structural modifications and quality control of proteins, cellular homeostasis, and metabolic pathways. The STRING database revealed the interactions between the regulated proteins. The GO enrichment analysis showed that 19 pathways were affected.</p><p><strong>Significance: </strong>The products released from the resin composite tested led to changes in the fibroblast proteome. Under the conditions of this study, resin composite released products can cause early adverse effects on cells, but without complete inhibition of their cellular functions.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400049"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473127","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}
{"title":"Advancements in Single-Cell Proteomics and Mass Spectrometry-Based Techniques for Unmasking Cellular Diversity in Triple Negative Breast Cancer.","authors":"Lakshmi Vineela Nalla, Aarika Kanukolanu, Madhuri Yeduvaka, Siva Nageswara Rao Gajula","doi":"10.1002/prca.202400101","DOIUrl":"10.1002/prca.202400101","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer characterized by a lack of targeted treatment options. Intratumoral heterogeneity significantly drives disease progression and complicates therapeutic responses, necessitating advanced analytical approaches to understand its underlying biology. This review aims to explore the advancements in single-cell proteomics and their application in uncovering cellular diversity in TNBC. It highlights innovations in sample preparation, mass spectrometry-based techniques, and the potential for integrating proteomics into multi-omics platforms.</p><p><strong>Methods: </strong>The review discusses the combination of improved sample preparation methods and cutting-edge mass spectrometry techniques in single-cell proteomics. It emphasizes the challenges associated with protein analysis, such as the inability to amplify proteins akin to transcripts, and examines strategies to overcome these limitations.</p><p><strong>Results: </strong>Single-cell proteomics provides a direct link to phenotype and cell behavior, complementing transcriptomic approaches and offering new insights into the mechanisms driving TNBC. The integration of advanced techniques has enabled deeper exploration of cellular heterogeneity and disease mechanisms.</p><p><strong>Conclusion: </strong>Despite the challenges, single-cell proteomics holds immense potential to evolve into a high-throughput and scalable multi-omics platform. Addressing existing hurdles will enable deeper biological insights, ultimately enhancing the diagnosis and treatment of TNBC.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400101"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682556","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}
Ling-Ling Jiao, Hui-Lin Dong, Yan-Hua Qin, Jun Zhu, Peng-Lin Wu, Jing Liu, Yi Cao, Chang-Jian Wu, Yuan Zhang, Fan Cao, Feng Li, Huai-Yuan Zhu
{"title":"Comparisons of Whole Saliva and Cell Free Saliva by DIA-Based Proteome Profiling.","authors":"Ling-Ling Jiao, Hui-Lin Dong, Yan-Hua Qin, Jun Zhu, Peng-Lin Wu, Jing Liu, Yi Cao, Chang-Jian Wu, Yuan Zhang, Fan Cao, Feng Li, Huai-Yuan Zhu","doi":"10.1002/prca.202400031","DOIUrl":"10.1002/prca.202400031","url":null,"abstract":"<p><strong>Background: </strong>Saliva has emerged as a promising diagnostic resource due to its accessibility, noninvasiveness, and repeatability, enabling early disease detection and timely intervention. However, current studies often overlook the distinction between whole saliva (WS) and cell-free saliva (CFS). Objective This study aims to compare the proteomic profiles of WS and CFS.</p><p><strong>Method and result: </strong>The saliva was detected with and without low-abundance protein enrichment using nanoparticles, employing DIA-MS technology. Our findings reveal a substantial enhancement in the detectability of low-abundance proteins in saliva with utilization of nanoparticles, enabling identification of 12%-15% low-abundance proteins previously undetectable in WS or CFS. In total, 3817 saliva proteins were identified, with 3413 found in WS and 2340 in CFS. More interestingly, we found that it was not the similarity of the samples that did the clustering, but rather it depended more on the different detection methods and sample types. And the predominant functions of the identified proteins in WS were related to oxidative phosphorylation and neurodegenerations, whereas those in CFS were primarily associated with nitrogen and glycosaminoglycan metabolism. And both exhibited functions in immune response and proteasome.</p><p><strong>Conclusion: </strong>This study represents the first comparison of WS and CFS, providing valuable experimental evidence for guiding the selection of research subjects in future saliva omics studies.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400031"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818982","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}
{"title":"Minimally Invasive Versus Invasive Proteomics: Urine and Blood Biomarkers in Coronary Artery Disease.","authors":"Rui Vitorino","doi":"10.1002/prca.202400062","DOIUrl":"10.1002/prca.202400062","url":null,"abstract":"<p><p>Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. This underlines the urgent need for effective biomarkers for early diagnosis, risk stratification, and therapeutic counseling. Proteomic signatures from plasma and urine have emerged as promising tools for these efforts, each offering unique advantages and challenges. This review provides a detailed comparison of urine and blood proteomic analyzes in the context of CAD and explores their respective advantages and limitations. Urine proteomics offers a minimally invasive, easily repeatable, and temporally stable sampling method, but faces challenges such as lower protein concentrations and potential contamination. Despite its invasive nature, blood proteomics captures high protein concentration and directly reflects systemic physiological changes, making it valuable for acute assessments. Advances in artificial intelligence (AI) have significantly improved the analysis and interpretation of proteomic data, enabling greater accuracy in diagnosis and predictive modeling. AI algorithms, particularly in pattern recognition and data integration, are helping to uncover subtle relationships between biomarkers and disease progression and supporting the discovery of plasma- and urine-based CAD biomarkers. This review demonstrates the potential of combining urine and blood proteomic data using AI to advance personalized approaches in CAD diagnosis and treatment. Future research should focus on standardization of collection protocols, validation of biomarkers in different populations, and the complexity of integrating data from different sources to maximize the potential of proteomics in the treatment of CAD.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400062"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740072","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}