A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study

Helfand, Brian T.; Andreev, Victor P.; Siddiqui, Nazema Y.; Liu, Gang; Erickson, Beth; Helmuth, Margaret E.; Lutgendorf, Susan K.; Lai, H. Henry; Kırkalı, Ziya

doi:10.1016/j.urology.2019.03.014

Cited by 9 publications

(3 citation statements)

References 22 publications

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“…Its quantitation quality is at least comparable/superior to other 'nonstandard' matrices e.g. urine/cerebrospinal fluid previously studied on this platform [56][57][58] . Our repeatability measures in pooled synovial fluid samples, with median %CVs of 11.25% for OA sample replicates and 12.42% for injury sample replicates, were higher than have been reported for plasma and serum samples measured using SomaScan technology, where %CVs of 5% or less are observed [59] .…”

Section: Discussionmentioning

confidence: 82%

Methodological development of molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: the STEpUP OA Consortium

Deng

Perry

Hulley

et al. 2023

Preprint

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Objectives: To develop and validate a pipeline for quality controlled (QC) protein data for largescale analysis of synovial fluid (SF), using SomaLogic technology. Design: Knee SF and associated clinical data were from partner cohorts. SF samples were centrifuged, supernatants stored at -80oC, then analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). Setting: An international consortium of 9 academic and 8 commercial partners (STEpUP OA). Participants: 1746 SF samples from 1650 individuals comprising OA, joint injury, healthy controls and inflammatory arthritis controls, divided into discovery (n=1045) and replication (n=701) datasets. Primary and secondary outcome measures: An optimised approach to standardisation was developed iteratively, monitoring reliability and precision (comparing coefficient of variation [%CV] of 'pooled' SF samples between plates and correlation with prior immunoassay for 9 analytes). Pre-defined technical confounders were adjusted for (by Limma) and batch correction was by ComBat. Poorly performing SOMAmers and samples were filtered. Variance in the data was determined by principal component (PC) analysis. Data were visualised by Uniform Manifold Approximation and Projection (UMAP). Results: Optimal SF standardisation aligned with that used for plasma, but without median normalisation. There was good reliability (<20 %CV for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. PC1 accounted for 48% of variance and strongly correlated with individual SOMAmer signal intensities (median correlation coefficient 0.70). These could be adjusted using an 'intracellular protein score'. PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation by UMAP revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. Conclusions: We define a standardised approach for SF analysis using the SOMAscan platform and identify likely 'intracellular' protein as being a major driver of variance in the data.

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Section: Discussionmentioning

confidence: 82%

Methodological development of molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: the STEpUP OA Consortium

Deng

Perry

Hulley

et al. 2023

Preprint

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“…Proteomics is an effective high‐throughput research mode, which is able to investigate the overall protein expression changes of the varieties and quantities dynamically and quantitatively, and to obtain some new protein markers as well as new key molecules. [ 16 ] It greatly enriches the optimal selections and combinations of diagnostic markers, which provides new ideas for us to seek specific diagnostic markers, [ 17 ] study the pathogenesis of the complex disease comprehensively, test the prognosis and recurrence of disease, and screen to identify the therapeutic targets. [ 18 ] Therefore, it is important to find out the most representative protein marker.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Blood Collection Tubes in Biomarkers’ Screening by Mass Spectrometry

Zhang

Zhao

Duan

et al. 2020

Proteomics Clinical Apps

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Purpose Mass spectrometry is one of the rapidly developing bio‐analytical techniques in recent years, and it shows that the results of biomarkers’ screening can be influenced by pre‐analytical process. The selection of the blood collection tubes is one of the most significant steps of pre‐analytical process which is often neglected by researchers. So, it is urgent to define the influence of blood collection tubes clearly in biomarkers’ screening. Experimental Design Two types of blood collection tubes, non‐additive tubes and coagulant activator tubes, are used to collect serum samples from patients and healthy controls. All samples are analyzed using matrix‐assisted laser desorption ionization‐time of flight mass spectrum in this study. Results The serum protein profile changes while using coagulant tubes whether for patients or healthy controls. It is found that the effect of coagulant on serum protein of patients is smaller than that of control group. There are 27 significantly different peaks between the control group and the control coagulant group. However, between patient group and patient coagulant group, only one differential peak is obtained. Coagulant changes the expression differences between patients and healthy controls, making the differences expand, shrink or reverse, and most of the polypeptides are small molecule, which will change the results of biomarker's screening. Conclusions and Clinical Relevance This research suggested that different types of blood collection tubes would influence the final laboratory results. So it's important for clinicians to choose the proper tubes to detect biomarkers and make correct diagnoses.

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“…The emerging technology, proteomics, is an effective high-throughput research mode, which is able to investigate the overall protein expression changes of the class and quantity dynamically and quantitatively, and to obtain some new protein markers as well as new key molecular 26,27 . It greatly enriches the optimal selections and combinations of diagnostic markers, which provides new ideas for us to seek specific diagnostic markers 28 , study the pathogenesis of the complex disease comprehensively, test the prognosis and recurrence of disease, and screen to identify the therapeutic targets 29 . Therefore, it's significant to find out the most representative protein marker.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Blood Collection Tubes in Biomarkers Screening by Mass Spectrometry

Zhang

Zhao

Duan

et al. 2019

Preprint

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AbstractBackgroundMass spectrometry (MS) is one of the rapidly developing bio-analytical techniques in recent years and have found many biomarkers of variety of disease. Whereas pre-analytical process is one of most crucial procedure which would significantly influence the results of biomarkers screening. In the current study, we conducted a pilot analysis of serum to determine the effects of blood collection tubes in biomarkers screening.MethodsMagnetic bead separation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for qualitative analysis of healthy control and serum cancer patients. A total of 24 serum samples were analyzed in this study, of which were collected from patients or healthy control using non-additive tubes or coagulant activator tubes respectively. ClinProTools were used to compare the difference among the different groups.ResultsThe results demonstrated that no matter for patients or normal people, the serum protein profile changed significantly when using coagulant tubes. We also found that the effect of coagulant on serum protein of patients was smaller than that of control group. There were significant differences among 27 peaks which were obtained in the control group and the control coagulant group. However, between patient group and patient coagulant group, only 1 differential peak were obtained. Coagulant changed the protein expression difference in the original serum, and the difference expanded, narrowed even reversed, most of which are small polypeptides (Mass<3000 Da), which significantly changed the results of biomarkers screening. The results showed that 19 potential biomarkers could be found with non-additive tubes and 16 potential biomarkers could be found with coagulate activator tubes, among which only 6 were the same.ConclusionsThe choice of blood collection tube significantly influence the results of biomarkers screening by MS.

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A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study

Cited by 9 publications

References 22 publications

Methodological development of molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: the STEpUP OA Consortium

Methodological development of molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: the STEpUP OA Consortium

The Influence of Blood Collection Tubes in Biomarkers’ Screening by Mass Spectrometry

The Influence of Blood Collection Tubes in Biomarkers Screening by Mass Spectrometry

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