Browse
Submit Data
Databases
API
Help

Dataset Information

308 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Plasma proteome profiling to detect and avoid sample-related biases in biomarker studies

ABSTRACT: Blood-based protein tests inform medical decision-making, but despite major investments, few new biomarkers reach the clinic. Plasma and serum are rich sources of information about an individual’s health state and mass spectrometry (MS)-based proteomics now allows highly specific and quantitative read-out of the plasma proteome. Here we employ plasma proteome profiling to define marker panels assessing the quality of plasma and serum samples and the likelihood that suggested biomarkers are instead artifacts related to sample handling and processing. We acquired reference proteomes of erythrocytes, platelets, plasma and whole blood of 20 individuals (>6000 proteins), and compared serum and plasma proteomes. Based on spike-in experiments we defined a panels of contamination-associated proteins, many of which have been reported as biomarker candidates. We provide sample preparation guidelines and an online resource (www.plasmaproteomeprofiling.com) to assess overall sample-related bias in clinical studies and to prevent costly miss-assignment of biomarker candidates.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, Blood Platelet, Blood Plasma, Blood Serum, Blood

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD011749 | Pride | 2018-11-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Blood.zip	Other
	Blood_20Ind_combined.zip	Other
	DilutionSeries_raw.zip	Other
	DilutionSeries_txt.zip	Other
	Erythrocytes_20Ind_combined.zip	Other

Items per page:

1 - 5 of 18

Similar Datasets

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

Project description:Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis, where treatment options are limited. As the liver secrets most of the blood plasma proteins its diseases should affect the plasma proteome. Plasma proteome profiling on 48 patients with cirrhosis or NAFLD with normal glucose tolerance or diabetes, revealed 8 significantly changing (ALDOB, APOM, LGALS3BP, PIGR, VTN, IGHD, FCGBP and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts with a 2.7-fold expression change in NAFLD and 4-fold change in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE to NAFLD and cirrhosis. DPP4 is a known drug target in diabetes. ANPEP and TGFBI are of interest because of their potential role in extracellular matrix remodeling in fibrosis.

2019-03-04 | PXD011839 | Pride

Plasma proteome profiling reveals global and specific changes of inflammatory and lipid homeostasis markers after bariatric surgery

Project description:Obesity-related diseases now affect half of the global population, and bariatric surgery is one of the few interventions with long lasting weight loss and cardio-metabolic effects. Here, we investigated the effect of Roux-en-Y gastric bypass surgery on the plasma proteome, hypothesizing that specific proteins or protein patterns may serve as key mediators and markers of the metabolic response. We performed MS-based proteomics on two longitudinal studies encompassing 47 morbidly obese patients, generating quantitative information on more than 1700 proteins. A global correlation matrix incorporating about 200,000 relationships revealed functional connections between proteins and assigned them to physiological processes. The main classes of significantly altered proteins were markers of systemic inflammation and those involved in lipid metabolism, and our data highlight robust correlative and anti-correlative behavior to each other and to clinical parameters. A group of inflammation-related proteins showed distinct inverse relationships to proteins consistently associated with insulin sensitivity.

2018-12-07 | PXD009348 | Pride

Human plasma LC-MS/MS from children with bacterial and viral infections

Project description:LC-MS/MS proteomic profiling was performed on children with bacterial and viral infections using plasma samples. Protein biomarkers indiciative of bacterial or viral infection were identified.

2023-11-14 | PXD041960 | Pride

Human plasma LC-MS/MS from children with bacterial and viral infections

2023-11-14 | PXD042003 | Pride

A comprehensive comparison of Rapid and Deep Plasma Proteomics workflows to identify and quantify biomarkers of Sickle Cell Anaemia

Project description:Plasma serves as a rich source of protein biomarkers but in-depth proteomic analysis is challenging due to the vast dynamic range of protein abundance. Pre-fractionation of plasma proteins is commonly practiced to improve the proteome coverage but the protocols are time-expensive, suffer from flowchart complexity, and often less reproducible. Here, we explore multiple strategies of shotgun proteomics to optimize biomarker discovery workflows for Sickle Cell Anaemia (SCA) patients from remote India. A deep proteomics workflow via off-line reverse phase Ultra High-Pressure Liquid Chromatography based fractionation of tryptic digested plasma peptides followed by optimized pooling of peptides based on charge and hydrophobicity yielded the best depth of plasma proteome with a trade-off of significantly long experimental time. Alternatively, a rapid analysis of tryptic digested plasma peptides via a shorter gradient mass spectrometry run saves time but quantifies only ~ 50% of the proteins than the deep workflow. Intriguingly, despite the difference in proteome coverage, more than 80% of known FDA and SCA biomarkers quantified in the deep workflow are also quantified in the rapid workflow. Given the practical difficulties of sample collection and plasma preservation in rural India, we propose the deep proteomics workflow for biomarker discovery in smaller cohorts and the rapid workflow for biomarker validations in larger cohorts. Additional targeted proteomics based strategies may be designed for the validation of missing biomarkers in the rapid workflow.

2024-04-04 | PXD035348 | Pride

Proteome-wide evaluation of plasma depletion methods vis-à-vis fractionation techniques

Project description:Human plasma is one of the most widely used tissues in clinical analysis, and plasma-based biomarkers are used for monitoring patient health status and/or response to medical treatment to avoid unnecessary invasive biopsy. Data driven plasma proteomics has suffered from a lack of throughput and detection sensitivity, largely due to the complexity of the plasma proteome, and in particular the enormous quantitative dynamic range, estimated to be between 9-13 orders of magnitude between the lowest and highest abundance protein. A major challenge is to identify workflows which can achieve depth of plasma proteome coverage, while minimizing the complexity of sample workup and maximizing sample throughput. In this study, we have performed intensive depletion of high abundant plasma proteins or enrichment of low abundant proteins using Hu6, Hu14 and ProteoMiner followed by SDS PAGE and C18 prefractionation techniques. We compared the performance of each of these fractionation approaches to identify the method which satisfies requirements for analysis of clinical samples, and to include good plasma proteome coverage in combination with reasonable sample output. In this study, we have reported that gel-based prefractionation approaches can replace expensive and time-consuming chromatographic separation, thereby significantly accelerating analysis time. In addition, we showed that a variety of methodologies can achieve similarly high proteome coverage, allowing flexibility depending on project specific needs. These considerations are important in the effort to accelerate plasma proteomics research so as to provide efficient, reliable and accurate diagnoses for the population as a whole.

2021-02-17 | PXD022469 | Pride

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

Project description:Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis, where treatment options are limited. As the liver secrets most of the blood plasma proteins, its diseases should affect the plasma proteome. Plasma Proteome Profiling of 48 patients with cirrhosis or NAFLD, revealed eight significantly changing (ALDOB, APOM, LGALS3BP, PIGR, VTN, IGHD, FCGBP and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts with a 2.7-fold expression change in NAFLD and 4-fold change in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE to NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP and LAP3, which all upregulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, Plasma Proteome Profiling can identify potential biomarkers and drug targets in liver disease.

2019-03-05 | PXD012056 | Pride

Human plasma LC-MSMS for predicting drug-response progonosis in depressed patients at 0, 1, 4 and 10 visiting weeks

Project description:Patients with major depressive disorder (MDD) have a high relapse rate and first prescribed selective serotonin reuptake inhibitors (SSRIs). The selection process of an antidepressant agent is primarily guided by trial and error. If patients do not benefit from the initial course of antidepressant medication for at least 4-6 weeks, additional therapeutic strategies are required to gain remission, including switching within and between classes of antidepressants. In order to discovery SSRI-related plasma protein markers, we designed a retrospective study. In this study, four longitudinal plasma samples were collected from 10 patients during the 10-week drug reaction period after being diagnosed with depression, and more than a thousand plasma proteins were identified by highly sensitive nanoflow liquid chromatography-tandem mass spectrometry (LC−MS/MS).

2020-11-03 | PXD017211 | Pride

Human plasma LC-MSMS for identified protein biomarker for BRCA1/2 positive ovarian cancer

Project description:Ovarian cancer (OC) is the most lethal gynecologic malignancy, attributed by late diagnosis. Genetic alteration of BRCA1/2 was well known risk factors in people who does not occur ovarian cancer. There is a need for convenient and continuous diagnosis of ovarian cancer after genetic testing, and we intend to apply a blood biomarker-based liquid biopsy. In a retrospective study, 20 OC patients and 20 normal controls were used for plasma samples, and BRCA1/2 carriers accounted for half in each group. We applied the bottom-up proteomics approach to depleted plasma samples with a nano-flow LC-MS and analyzed protein data quantitatively.

2021-06-07 | PXD023508 | Pride

Progresses and challenges of Strongyloides spp. proteomics

Project description:The availability of high-quality data of helminth genomes provided over the last two decades has supported and accelerated large-scale ‘omics studies and, consequently, the achievement of a more in depth molecular characterisation of a number of pathogens. Strongyloides spp. are no less and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle. Strongyloides proteomics characterisation has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host-parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterisation of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis.

2024-01-26 | PXD041218 | Pride