Colin K Kim, Mak B Djulbegovic, David Broytman, Nedym Hadzijahic, Michael Antonietti, David J Taylor Gonzalez, Vladimir N Uversky, Nicolas A Yannuzzi, Carol L Karp
{"title":"Bioinformatics-Based Comparative Analysis of the Human Retina Proteome.","authors":"Colin K Kim, Mak B Djulbegovic, David Broytman, Nedym Hadzijahic, Michael Antonietti, David J Taylor Gonzalez, Vladimir N Uversky, Nicolas A Yannuzzi, Carol L Karp","doi":"10.1002/prca.70012","DOIUrl":"https://doi.org/10.1002/prca.70012","url":null,"abstract":"<p><strong>Introduction: </strong>The human retina relies on a complex network of proteins, many of which exhibit intrinsic disorder and liquid-liquid phase separation (LLPS), enabling dynamic interactions for retinal function. Disruptions in these properties, along with missense mutations, have been linked to retinal diseases. This study aims to characterize and compare retinal proteins categorized by their expression specificity and tissue distribution using bioinformatics tools to explore relationships between intrinsic protein disorder, phase separation potential, and mutation pathogenicity.</p><p><strong>Methods: </strong>We analyzed retinal proteins classified by the Human Protein Atlas (HPA) into two major groups based on gene expression specificity (degree of unique retinal expression) and gene expression distribution (extent of expression across tissues). We analyzed nine retinal proteomes categorized by gene expression specificity and distribution. Intrinsic protein disorder was assessed using per-residue and global disorder predictors from the Rapid Intrinsic Disorder Analysis Online (RIDAO) platform, LLPS potential was evaluated with ParSe v2, and missense mutation pathogenicity was predicted using AlphaMissense.</p><p><strong>Results: </strong>Significant differences in per-residue intrinsic protein disorder were found within the specificity and distribution subgroups (p < 0.0001). In addition, global disorder predictions from the RIDAO platform demonstrated non-random distributions of protein species across the proteomes analyzed in both subgroups (p < 0.0001). Furthermore, proteins specifically elevated in the retina exhibited higher intrinsic disorder and greater phase separation propensity (ParSe v2, AUC up to 0.650), compared to those more broadly expressed. Lastly, AlphaMissense analysis showed significant variations in the average pathogenicity scores of missense mutations within subgroups (p < 0.0001).</p><p><strong>Conclusion: </strong>Our results show that intrinsic disorder, LLPS, and mutational tendencies are not evenly distributed among retinal proteomes. Our study demonstrates a link between intrinsic disorder, LLPS potential, and pathogenic vulnerability among retinal proteins, underscoring the unique structural and functional landscape of retinal proteomes. Proteins with higher specificity to the retina exhibit greater disorder and phase separation potential, highlighting their potential role in dynamic cellular processes that support retinal function. Conversely, proteins widely distributed across multiple tissues tend to be more ordered, suggesting a need for structural stability in their broader functional roles.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70012"},"PeriodicalIF":2.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249353","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":"Classification of Acid and Alkaline Enzymes Based on Normalized Van der Waals Volume Features.","authors":"Hao Wan, Quan Zou, Yanan Zhang","doi":"10.1002/prca.70009","DOIUrl":"https://doi.org/10.1002/prca.70009","url":null,"abstract":"<p><strong>Objective: </strong>Acidic and alkaline enzymes play crucial roles in the food industry and environmental management. This study aims to develop a computational method for accurately distinguishing between acidic and alkaline enzymes to enhance their stability in varying pH environments.</p><p><strong>Methods: </strong>We employed AutoProp for feature extraction and the MRMD3.0 algorithm for feature selection. The most discriminative feature, the normalized Van der Waals volume (nFeat43), was identified and used for classification.</p><p><strong>Results: </strong>The selected feature (nFeat43) achieved a classification accuracy of 76.2% in distinguishing acidic from alkaline enzymes. Further analysis was conducted to interpret the physicochemical significance of this feature in enzyme discrimination.</p><p><strong>Conclusions: </strong>Our findings demonstrate that nFeat43 is a key determinant in differentiating acidic and alkaline enzymes. This method provides a rapid and reliable computational approach for enzyme characterization, which could aid in industrial and environmental applications.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70009"},"PeriodicalIF":2.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192075","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}
Takumi Tsutaya, Kana Fujimoto, Yusuke Nakai, Naana Mori, Ran Iguchi, Akinori Moroi, Kunio Yoshizawa, Koichiro Ueki, Yayoi Kimura, Noboru Adachi
{"title":"Proteomic Investigation of Human Dental Pulp to Identify Individuals Who Are Pregnant.","authors":"Takumi Tsutaya, Kana Fujimoto, Yusuke Nakai, Naana Mori, Ran Iguchi, Akinori Moroi, Kunio Yoshizawa, Koichiro Ueki, Yayoi Kimura, Noboru Adachi","doi":"10.1002/prca.70011","DOIUrl":"https://doi.org/10.1002/prca.70011","url":null,"abstract":"<p><p>Biomolecules preserved in dental pulp are increasingly being used to identify individuals in the context of forensics and archaeology. Despite the vast amount of research into host and pathogen DNA, the potential use of physiologically informative proteins preserved in dental pulp has rarely been studied. Here, we hypothesized that pregnancy-specific proteins circulating in the blood could be identified from the dental pulp of postpartum individuals and this was investigated using eight human third molars extracted from four postpartum and three control individuals during clinical treatment. A total of 885 proteins were identified from these eight dental pulp samples using liquid chromatography coupled tandem mass spectrometry, whose gene ontology compositions were similar to previous studies. However, despite our hypothesis, pregnancy-specific proteins were not identified from the dental pulp of postpartum individuals (n = 5, 4-12 months postpartum). Although the dental pulp proteomes obtained from three individuals postpartum ≤6 months were distinct from those of other individuals by principal component analysis (PCA), their driving proteins were less evident. Although our hypothesis was not supported, sample collection, protein extraction, and mass spectrometry analysis could be improved to explore the forensic application of detecting pregnancy-specific proteins in dental pulp.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70011"},"PeriodicalIF":2.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192076","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}
Jeong Min Cho, Minsang Kim, Jaeik Oh, Jung Hun Koh, Semin Cho, Yaerim Kim, Soojin Lee, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Kwon-Wook Joo, Yon Su Kim, Hajeong Lee, Dong Ki Kim, Sehoon Park
{"title":"Causal Effects From Kidney Function to Plasma Proteome: Integrated Observational and Mendelian Randomization Analysis With >50,000 UK Biobank Participants.","authors":"Jeong Min Cho, Minsang Kim, Jaeik Oh, Jung Hun Koh, Semin Cho, Yaerim Kim, Soojin Lee, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Kwon-Wook Joo, Yon Su Kim, Hajeong Lee, Dong Ki Kim, Sehoon Park","doi":"10.1002/prca.70002","DOIUrl":"10.1002/prca.70002","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic kidney disease (CKD) causes detrimental systemic effects, including inflammation or apoptosis, which lead to substantial morbidity and mortality. However, the causal effect of reduced kidney function on systemic proteomic signatures is incompletely understood.</p><p><strong>Methods: </strong>We performed an integrated Mendelian randomization (MR) and observational analyses to identify the causal association between kidney function and plasma protein levels, based on 1815 plasma protein profiles in 50,407 UK Biobank participants and the CKDGen Phase 4 genome-wide association study (GWAS) meta-analysis for the genetic instruments of eGFR.</p><p><strong>Results: </strong>The MR analysis revealed 383 plasma proteins causally associated with eGFR. Reduced kidney function was found to be causally associated with an increase in the plasma levels of 381 proteins, among which TNF and IGFBP4 were increased, while the level of two proteins, NPHS1 and SPOCK1, decreased. Apoptosis-related pathway was significantly enriched in the gene-set enrichment analysis. In network analysis, TNF was identified as a hub protein with multiple linkages to molecules included in the TNF-signaling pathways, involved in inflammation, fibrosis, and apoptosis.</p><p><strong>Conclusions: </strong>In this proteo-genomic analysis, we identified 383 plasma proteins causally associated with eGFR, highlighting TNF-associated pathways as pathologically relevant processes in kidney disease progression, systemic inflammation, and organ fibrosis, warranting further investigation.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70002"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524224","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}
Eleni Skandalou, Mariell Rivedal, Hans-Peter Marti, Thea A S Halden, Trond Jenssen, Bjørn Egil Vikse, Anders Åsberg, Jessica Furriol
{"title":"Proteome of Renal Tubuli and Serum Differentiate Pre-Existing Type 2 Diabetes and Post-Transplant Diabetes in Kidney Transplant Recipients.","authors":"Eleni Skandalou, Mariell Rivedal, Hans-Peter Marti, Thea A S Halden, Trond Jenssen, Bjørn Egil Vikse, Anders Åsberg, Jessica Furriol","doi":"10.1002/prca.70000","DOIUrl":"10.1002/prca.70000","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD), with kidney transplantation being the preferred treatment. However, post-transplant diabetes mellitus (PTDM) increases mortality and graft loss. While PTDM and Type 2 diabetes mellitus (T2DM) share risk factors, their mechanisms differ, particularly in diabetic nephropathy (DN). This study aimed to investigate the molecular differences in PTDM by mapping the proteomes of proximal tubuli and serum in normoglycemic (NG), pre-transplant T2DM, and PTDM patients one year post-transplantation. Experimental Design Proteomic analysis was performed on microdissected proximal tubular cells and serum samples from kidney transplant recipients categorized as NG, pre-transplant T2DM, or PTDM at one year post-transplantation. Mass spectrometry was used to identify differentially expressed proteins. Data analyses were performed using gene ontology databases and pathway analysis.</p><p><strong>Results: </strong>Proteomic analysis revealed key differences, including significant dysregulation of mitochondrial proteins and lipid metabolism pathways in PTDM patients compared to T2DM and NG groups. Additionally, we observed distinct serum patterns of cholesterol metabolism dysregulation in PTDM, highlighting a complex interplay between fatty acid metabolism, mitochondrial dysfunction and systemic lipid dysregulation that may drive renal injury in PTDM-related DN.</p><p><strong>Conclusions and clinical relevance: </strong>This pilot study is the first to perform proteomic analysis on both microdissected tubular cells and serum from post-transplant PTDM, pre-transplant T2DM and NG transplant recipients. The proteomic differences between PTDM and T2DM could help to develop targeted therapies and early diagnostic markers, ultimately improving transplant outcomes and patient management. Further research is needed to validate these findings and explore their therapeutic potential.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70000"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483804","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}
Priyanka Boettger, Hansjörg Schwertz, Herbert Platsch, Ursula Mueller-Werdan, Karl Werdan, Michael Buerke
{"title":"Intramural Administration of Translational Inhibitor Puromycin Upon Balloon Angioplasty Inhibits SMC Proliferation and Protein Synthesis-Vascular Proteome Profiling Analysis.","authors":"Priyanka Boettger, Hansjörg Schwertz, Herbert Platsch, Ursula Mueller-Werdan, Karl Werdan, Michael Buerke","doi":"10.1002/prca.202400066","DOIUrl":"10.1002/prca.202400066","url":null,"abstract":"<p><strong>Introduction: </strong>Percutaneous transluminal coronary angioplasty (PTCA) is an effective procedure to decrease the severity of stenotic coronary atherosclerotic lesions. However, its long-term success is limited by the formation of restenosis or neointima by increased proliferation of smooth muscle cells (SMCs) and synthesis of extracellular matrix. Polypeptide growth factors are potent SMC mitogens and are involved in SMC proliferation and extracellular matrix (ECM) synthesis. In this line, inhibition of de novo protein synthesis might be beneficial.</p><p><strong>Methods: </strong>We examined the effects of different concentrations of translational inhibitor puromycin on SMC proliferation and apoptosis, in vitro. Further, we examined the effects of local administration of puromycin in a rabbit balloon injury model of the iliac artery.</p><p><strong>Results: </strong>Injection of puromycin or its vehicle was performed with an infusion-balloon catheter directly into the vessel wall during angioplasty. PTA in the vehicle group resulted in neointima formation 3 weeks after the vascular intervention. In contrast, puromycin treatment resulted in a significant reduction of intima-media ratio. We observed decreased elastin and collagen III synthesis in puromycin-treated animals. With proteomics, we could demonstrate reduced protein expression of lamin, vimentin, alpha-1 antitrypsin, alpha-actin allowing puromycin treatment. In in vitro experiments, puromycin decreased SMCs proliferation (i.e., BrdU incorporation) following FCS stimulation.</p><p><strong>Perspective: </strong>Based on the data from our animal experiments, aministration of puromycin directly into the vessel wall during angioplasty may be effective in preventing or reducing restenosis in humans.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400066"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493442","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}
Sarah Martins Presti-Silva, Lucas Rodrigues-Ribeiro, Vladimir Gorshkov, Frank Kjeldsen, Thiago Verano-Braga, Rita Gomes Wanderley Pires
{"title":"Proteomic Analysis of Substantia Nigra Reveals Molecular Insights Into the Neuroprotection Effect of Rosmarinic Acid Treatment in MPTP-Induced Mouse Model of Parkinson's Disease.","authors":"Sarah Martins Presti-Silva, Lucas Rodrigues-Ribeiro, Vladimir Gorshkov, Frank Kjeldsen, Thiago Verano-Braga, Rita Gomes Wanderley Pires","doi":"10.1002/prca.70006","DOIUrl":"10.1002/prca.70006","url":null,"abstract":"<p><strong>Purpose: </strong>Parkinson's disease (PD) is neuropathologically characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), affecting 10 million people worldwide. Rosmarinic acid (RA), a polyphenol found in plants like rosemary (Rosmarinus officinalis), is known for its intriguing biological properties and potential antioxidant and neuroprotective effects. In a previous study we showed that RA treatment prevented hyperlocomotion in mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced parkinsonism and improved the monoaminergic system in healthy animals. However, the molecular mechanisms underlying RA's action in PD remain unclear.</p><p><strong>Experimental design: </strong>In this study, we treated MPTP-induced PD animals (C57BL/6 male mice) with RA orally at a dose of 100 mg/kg for 15 days and examined the proteome of substantia nigra (SN) to identify possible regulatory targets of RA treatment to shed some lights into its neuroprotective effects.</p><p><strong>Results: </strong>Quantitative proteomics revealed that RA treatment regulated proteins associated with oxidative phosphorylation (OXPHOS), glutamatergic synapse, and vesicular cycle signaling pathway. We identified 371 proteins significantly regulated in response to RA administration (255 upregulated and 116 downregulated). Notably, some cellular targets of RA treatment reported here, including mGluR2/mGluR3/EAAT-proteins from the glutamatergic system-and proteins from the Complex I of the electron transport chain are promising targets for therapeutic intervention.</p><p><strong>Conclusions and clinical relevance: </strong>These findings highlight the molecular differences between MPTP-induced PD mice and those treated with RA, providing insights on the molecular basis behind the neuroprotective effects of RA and revealing potential PD signatures that warrant further investigation.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70006"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780957","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}
Razan Elkahlout, Sawsan G A A Mohammed, Ahmed Najjar, Thomas Farrell, Hilal Al Rifai, Nader Al-Dewik, M Walid Qoronfleh
{"title":"Application of Proteomics in Maternal and Neonatal Health: Advancements and Future Directions.","authors":"Razan Elkahlout, Sawsan G A A Mohammed, Ahmed Najjar, Thomas Farrell, Hilal Al Rifai, Nader Al-Dewik, M Walid Qoronfleh","doi":"10.1002/prca.70004","DOIUrl":"10.1002/prca.70004","url":null,"abstract":"<p><p>Maternal and neonatal health (women during pregnancy, childbirth, and the postnatal period) presents a spectrum of healthcare challenges, including preterm birth, preeclampsia, intrauterine growth restriction, polycystic ovarian syndrome, and gestational diabetes mellitus. While genomic investigations have shed light on many of these topics, protein biomarker discovery, a pivotal aspect of such research, holds promise in offering insights into disease diagnosis, progression, and prognosis. This review paper aims to explore the landscape of proteomics research pertaining to the aforementioned disorders. In the search for viable biomarkers, existing ones are either outdated or lack specificity and new ones being investigated do not commonly make it to the validation stage. In this review, the reasons for the gap between the biomarker discovery stage and the clinical validation stage are evaluated, in addition to what steps are being taken to mitigate the unexpectedly slow scientific and clinical progress. Notably, this paper also delves into the ethnic disparities found in maternal and neonatal health research, as well as how AI is currently being used to alleviate socioeconomic and ethnic disparities, as well as its advantages for the analysis of large \"omics\" datasets. We anticipate this investigation will provide critical, invaluable information for researchers, medical professionals, and policy decision-makers in this field to improve overall maternal and neonatal health outcomes.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70004"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701378","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}
Van Duc Pham, Jung-Hyung Lee, Doyun Shin, Hung M Vu, Junyang Jung, Manoj K Kashyap, Seung Hyeun Lee, Min-Sik Kim
{"title":"On the Ocean of Biomarkers for the Precise Diagnosis and Prognosis of Lung Diseases.","authors":"Van Duc Pham, Jung-Hyung Lee, Doyun Shin, Hung M Vu, Junyang Jung, Manoj K Kashyap, Seung Hyeun Lee, Min-Sik Kim","doi":"10.1002/prca.70003","DOIUrl":"10.1002/prca.70003","url":null,"abstract":"<p><p>Bronchoalveolar lavage fluid (BALF) has long been used for diagnosing various lung diseases through its cellular components. However, the clinical utility of biomolecules in the BALF remains largely unexplored. Recently, mass spectrometry-based proteomics has been applied to profile the BALF proteomes to identify novel biomarkers for lung diseases. This review discusses the current progress in the field of BALF proteomics and highlights its potential as a valuable source of biomarkers for different lung diseases. Additionally, we explored the latest advancements and findings from BALF studies. Finally, we address the current limitations and propose future directions and research opportunities to advance the study of BALF.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70003"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650071","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}
Valerie K Sullivan, Jingsha Chen, Lauren Bernard, Bing Yu, Erin D Michos, Lawrence J Appel, Alice H Lichtenstein, Casey M Rebholz
{"title":"Proteomic Correlates of Vitamin D Supplementation in the Atherosclerosis Risk in Communities (ARIC) Study.","authors":"Valerie K Sullivan, Jingsha Chen, Lauren Bernard, Bing Yu, Erin D Michos, Lawrence J Appel, Alice H Lichtenstein, Casey M Rebholz","doi":"10.1002/prca.70005","DOIUrl":"10.1002/prca.70005","url":null,"abstract":"<p><strong>Purpose: </strong>Proteins are key effectors of biological functions and play roles in signaling, transport, growth, repair, and immunity. Vitamin D biomarkers may be reflected in the plasma proteome. The aim of this discovery study was to identify novel proteins associated with vitamin D supplementation.</p><p><strong>Experimental design: </strong>We examined cross-sectional associations between vitamin D supplementation and plasma proteins in the Atherosclerosis Risk in Communities (ARIC) study at visit 5 (2011-2013). An untargeted proteomic platform (SomaScan version 4, SomaLogic) was used to quantify relative abundance for 4955 proteins. We compared protein levels in vitamin D supplement users and nonusers using covariate-adjusted multivariable linear regression models.</p><p><strong>Results: </strong>Of 5011 participants analyzed (mean age 76 [SD 5] years), 2255 (45%) used vitamin D supplements. Fifty-one proteins were associated with vitamin D supplementation at a false discovery rate-adjusted p < 0.05. Most proteins (33 of 51) were lower in users than nonusers. After adjusting for other supplement use (multivitamin/mineral, omega-3, B vitamins, and vitamin C), 7 proteins remained significantly associated with vitamin D supplementation.</p><p><strong>Conclusions and clinical relevance: </strong>Chondroadherin, parathyroid hormone, transcobalamin-1, osteomodulin, collagen type II, and bone sialoprotein 2 were lower, while sclerostin was higher, in vitamin D users than nonusers. These proteins are potential markers of vitamin D in older adults and highlight vitamin D-related metabolic pathways.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e70005"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670372","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}