Clinical applications of plasma proteomics and peptidomics: Towards precision medicine

PROTEOMICS - CLINICAL APPLICATIONS, Journal Year: 2022, Volume and Issue: 16(6)

Published: May 1, 2022

In the context of precision medicine, disease treatment requires individualized strategies based on underlying molecular characteristics to overcome therapeutic challenges posed by heterogeneity. For this purpose, it is essential develop new biomarkers diagnose, stratify, or possibly prevent diseases. Plasma an available source that greatly reflects physiological and pathological conditions body. An increasing number studies are focusing proteins peptides, including many involving Human Proteome Project (HPP) Organization (HUPO), proteomics peptidomics techniques emerging as critical tools for developing novel medicine preventative measures. Excitingly, plasma toolbox exhibits a huge potential studying pathogenesis diseases (e.g., COVID-19 cancer), identifying valuable improving clinical management. However, enormous complexity wide dynamic range makes proteome profiling challenging. Herein, we summarize recent advances in with focus their roles cancer research, aiming emphasize significance applications medicine.

Language: Английский

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Recent developments and applications of capillary and microchip electrophoresis in proteomics and peptidomics (mid‐2018–2022)

Journal of Separation Science, Journal Year: 2023, Volume and Issue: 46(12)

Published: Feb. 26, 2023

This review gives a wide overview of recent advances and applications capillary electrophoresis microchip methods in the fields proteomics peptidomics period from mid‐2018 up to end 2022. The methodological topics covering sample preparation concentration techniques, hyphenation with mass spectrometry, multidimensional separations by on‐line or off‐line coupled different liquid chromatography techniques are described new developments both bottom‐up top‐down approaches presented. In addition, various proteomic peptidomic studies demonstrated. They include monitoring protein posttranslational modifications biological biochemical research, clinical proteomics, food analysis.

Language: Английский

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Sample preparation and fractionation techniques for intact proteins for mass spectrometric analysis

Journal of Separation Science, Journal Year: 2020, Volume and Issue: 44(1), P. 211 - 246

Published: Nov. 2, 2020

The analysis of proteins in biological samples is highly desirable, given their connection to myriad functions and disease states, as well the growing interest development protein-based pharmaceuticals. introduction maturation "soft" ionization methods, such electrospray matrix-assisted laser desorption/ionization, have made mass spectrometry an indispensable tool for proteins. Despite availability powerful instrumentation, sample preparation fractionation remain among most challenging aspects protein analysis. This review summarizes these challenges provides overview state-of-the-art spectrometric analysis, with emphasis on those used top-down proteomic approaches. Biological fluids, particularly important clinical pharmaceutical applications characteristics are also discussed. While immunoaffinity-based methods addressed, more attention non-immunoaffinity-based precipitation, coacervation, size exclusion, dialysis, solid-phase extraction, electrophoresis. These techniques presented context a significant number studies where they been developed utilized.

Language: Английский

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Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease

PROTEOMICS - CLINICAL APPLICATIONS, Journal Year: 2020, Volume and Issue: 15(1)

Published: July 25, 2020

Abstract Urinary peptides gained significant attention as potential biomarkers especially in the context of kidney and cardiovascular disease. In this manuscript recent literature since 2015 on urinary peptide investigation human disease is reviewed. The technology most commonly used capillary electrophoresis coupled mass spectrometry, part owed to large database available well‐defined dataspace. Several studies based over 1000 subjects are reported past, examining CKD273, a classifier for assessment chronic 273 urine peptides. Interestingly, abundant generally collagen fragments, which may have gone undetected some time they typically modified via proline hydroxylation. data suggest that specifically depict inflammation fibrosis, serve non‐invasive tool assess appears be key driver successful completion first guided intervention trial, PRIORITY, expected further spur clinical application peptidomics, aiming at early detection diseases, prediction progression, prognosis drug response.

Language: Английский

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Reproducibility Evaluation of Urinary Peptide Detection Using CE-MS

Molecules, Journal Year: 2021, Volume and Issue: 26(23), P. 7260 - 7260

Published: Nov. 30, 2021

In recent years, capillary electrophoresis coupled to mass spectrometry (CE-MS) has been increasingly applied in clinical research especially the context of chronic and age-associated diseases, such as kidney disease, heart failure cancer. Biomarkers identified using this technique are already used for diagnosis, prognosis monitoring these complex well patient stratification trials. CE-MS allows a comprehensive assessment small molecular weight proteins peptides (<20 kDa) through combination high resolution reproducibility CE distinct sensitivity MS, high-throughput system. study we assessed analytical performance with regards its inter- intra-day reproducibility, variability efficiency peptide detection, along characterization urinary peptidome content. To end, was evaluated based on 72 measurements standard urine sample (60 12 assessment) analyzed during second quarter 2021. Analysis performed per run, peptide, at level biomarker panels. The obtained datasets showed correlation between different runs, low variation ten highest average individual log2 signal intensities (coefficient variation, CV < 10%) very panels (CV close 1%). findings support CE-MS, underlining value application.

Language: Английский

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A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease

Proteomes, Journal Year: 2021, Volume and Issue: 9(3), P. 32 - 32

Published: July 13, 2021

Non-invasive urinary peptide biomarkers are able to detect and predict chronic kidney disease (CKD). Moreover, specific peptides enable discrimination of different CKD etiologies offer an interesting alternative invasive biopsy, which cannot always be performed. The aim this study was define a classifier using mass spectrometry technology the degree renal interstitial fibrosis tubular atrophy (IFTA) in patients. profiles 435 patients enrolled were analyzed capillary electrophoresis coupled with (CE-MS). Urine samples collected on day diagnostic biopsy. proteomics data divided into training (

Language: Английский

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Urinary peptidomic profiles to address age-related disabilities: a prospective population study

The Lancet Healthy Longevity, Journal Year: 2021, Volume and Issue: 2(11), P. e690 - e703

Published: Oct. 16, 2021

BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2019 called for innovation in addressing age-related disabilities. Our study aimed to identify validate a urinary peptidomic profile (UPP) differentiating healthy from unhealthy ageing the general population, test UPP predictor independent patient cohorts, search targetable molecular pathways underlying chronic diseases.MethodsIn this prospective population study, we used data participants Flemish on Environment, Genes Health Outcomes (FLEMENGHO), done northern Belgium 1985 2019, invited follow-up examination 2005–10. Participants were eligible if their address was within 15 km centre they had not withdrawn consent any previous cycles (1985–2004). All (2005–10) also an additional 2009–13. who took part both 2005–10 2009–13 visit constituted derivation dataset, which included data, time-shifted internal validation data. The remaining only synchronous dataset. excluded analyses incapacitated, undergone UPP, or either missing outlying (three SDs greater than mean all consenting participants) values body-mass index, plasma glucose, serum creatinine. assessed by capillary electrophoresis coupled with mass spectrometry. multidimensional signature reflecting generated dataset validated It further patients diabetes, COVID-19, kidney disease (CKD). In FLEMENGHO, mortality endpoints all-cause, cardiovascular, non-cardiovascular mortality; other fatal non-fatal cancer musculoskeletal disorders. Molecular pathway exploration using Reactome Kyoto Encyclopedia Genomes databases.Findings778 individuals (395 [51%] women 383 [49%] men; aged 16·2–82·1 years; age 50·9 years [SD 15·8]) FLEMENGHO cohort between 2005 2010, whom 559 Oct 28, 2009, March 19, 2013, made up (2009–13) datasets. 219 examined once (2005–10). With correction multiple testing multivariable adjustment, chronological associated 210 sequenced peptides mainly showing downregulation collagen fragments. trained model relating derived elastic net regression, 54 17 proteins. UPP-age prediction explained 76·3% (r=0·87) 54·4% (r=0·74) 65·3% (r=0·81) Compared age, predicted diabetes (chronological 50·8 [SE 0·37] vs 56·9 [0·30]), COVID‑19 (53·2 [1·80] 58·5 [1·67]), CKD (54·6 [0·97] 62·3 [0·85]; p<0·0001). cohort, significantly various risk markers related metabolic, renal disease, inflammation, medication use. Over median 12·4 (IQR 10·8–13·2), total mortality, cardiovascular osteoporosis hazard ratios per 10 year increase 1·54 (95% CI 1·22–1·95) 1·72 (1·20–2·47) 1·40 (1·06–1·85) fractures. most relevant informed proteins involved deregulation biology extracellular matrix maintenance.InterpretationThe indicative reflects fibrosis remodelling factors adverse health outcomes accelerated patients. Innovation disability should shift focus ontology diseases shared mechanisms, particular ageing-related fibrotic degeneration.FundingEuropean Research Council, Ministry Community, OMRON Healthcare.

Language: Английский

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Collagen-Derived Peptides in CKD: A Link to Fibrosis

Toxins, Journal Year: 2021, Volume and Issue: 14(1), P. 10 - 10

Published: Dec. 23, 2021

Collagen is a major component of the extracellular matrix (ECM) and has an imminent role in fibrosis, in, among others, chronic kidney disease (CKD). alpha-1(I) (col1a1) most abundant collagen type previously been underlined for its contribution to phenotype. Here, we examined 5000 urinary peptidomic datasets randomly selected from healthy participants or patients with CKD identify col1a1 fragments study their abundance, position main protein, as well correlation renal function. We identified 707 peptides that differed amino acid sequence and/or post-translational modifications (hydroxyprolines). Well-correlated same sequence, but different number hydroxyprolines, were combined into final list 503 peptides. These covered 69% full sequence. Sixty-three significantly highly positively associated (rho > +0.3) estimated glomerular filtration rate (eGFR), while only six showed significant strong, negative association < −0.3). A similar tendency was observed ageing, where abundance decreased increasing age. Collectively results show strong between loss function suggest potentially also other organs, may be consequence attenuation degradation, not increased synthesis.

Language: Английский

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Mass Spectrometry-Based Biomarkers to Detect Prostate Cancer: A Multicentric Study Based on Non-Invasive Urine Collection without Prior Digital Rectal Examination

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1166 - 1166

Published: Feb. 11, 2023

(1) Background: Prostate cancer (PCa) is the most frequently diagnosed in men. Wide application of prostate specific antigen test has historically led to over-treatment, starting from excessive biopsies. Risk calculators based on molecular and clinical variables can be value determine risk PCa as such, reduce unnecessary invasive Urinary studies have been mostly focusing sampling after initial intervention (digital rectal examination and/or massage). (2) Methods: Building previous proteomics studies, this manuscript, we aimed at developing a biomarker model for detection urine without prior intervention. Capillary electrophoresis coupled mass spectrometry was applied acquire profiles 970 patients two different centers. (3) Results: A case-control comparison performed training set 413 181 significant peptides were subsequently combined by support vector machine algorithm. Independent validation initially 272 negative 138 biopsy-confirmed PCa, resulting an AUC 0.81, outperforming current standards, while second phase included 147 patients. (4) Conclusions: This multi-dimensional holds promise improve diagnosis guiding

Language: Английский

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Prediction of coronary artery disease using urinary proteomics

European Journal of Preventive Cardiology, Journal Year: 2023, Volume and Issue: 30(14), P. 1537 - 1546

Published: March 20, 2023

Coronary artery disease (CAD) is multifactorial, caused by complex pathophysiology, and contributes to a high burden of mortality worldwide. Urinary proteomic analyses may help identify predictive biomarkers provide insights into the pathogenesis CAD.Urinary proteome was analysed in 965 participants using capillary electrophoresis coupled with mass spectrometry. A classifier developed discovery cohort 36 individuals CAD matched controls support vector machine. The tested validation 115 who progressed 778 compared two previously CAD-associated classifiers, CAD238 ACSP75. Framingham SCORE2 risk scores were available 737 participants. Bioinformatic analysis performed based on peptides. novel comprised 160 urinary peptides, mainly related collagen turnover, lipid metabolism, inflammation. In cohort, provided an area under receiver operating characteristic curve (AUC) 0.82 [95% confidence interval (CI): 0.78-0.87] for prediction 8 years, superior (AUC: 0.71, 95% CI: 0.66-0.77) ACSP75 0.53 0.47-0.60). On top ACSP75, addition improved AUC 0.84 (95% 0.80-0.89). multivariable Cox model, 1-SD increment associated higher (HR: 1.54, 1.26-1.89, P < 0.0001). new further reclassification or (net index: 0.61, 0.25-0.95, = 0.001; 0.64, 0.28-0.98, 0.001, correspondingly).A lipids, inflammation showed potential CAD. provides alternative approach personalized prevention.A biomarker that can predict coronary urgently need. We validated involved atherosclerosis clinical score.

Language: Английский

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