Plasma Proteome Profiling Reveals Dynamics of Inflammatory and Lipid Homeostasis Markers after Roux-En-Y Gastric Bypass Surgery

Albrechtsen, Nicolai J. Wewer; Geyer, Philipp; Doll, Sophia; Treit, Peter V.; Bojsen‐Møller, Kirstine N.; Martinussen, Christoffer; Jørgensen, Nils B.; Torekov, Signe S.; Meier, Florian; Niu, Lili; Santos, Alberto; Keilhauer, Eva C.; Holst, Jens J.; Madsbad, Sten; Mann, Matthias

doi:10.1016/j.cels.2018.10.012

Cited by 84 publications

(96 citation statements)

References 49 publications

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“…We found that bariatric surgery not only induced significant changes in plasma biochemistry parameters, as already established (Wewer Albrechtsen et al, 2018), but it had a profound effect on transcriptional and active chromatin landscapes. We found genes that, after bariatric surgery, revert to the expression level observed in lean individuals.…”

Section: Effect Of Bariatric Surgerysupporting

confidence: 66%

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Seyres¹,

Cabassi

Lambourne³

et al. 2020

Preprint

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Providing a molecular characterisation of cardiometabolic syndrome (CMS) could improve our understanding of its pathogenesis and pathophysiology, and provide a step toward the development of better treatments. To this end, we performed a deep phenotyping analysis of 185 blood donors, 10 obese, and 10 lipodystrophy patients.We analysed transcriptomes and epigenomes of monocytes, neutrophils, macrophages and platelets. Additionally, plasma metabolites including lipids and biochemistry measurements were quantified.Multi-omics integration of this data allowed us to identify combinations of features related to patient status and to order the donor population according to their molecular similarity to patients. We also performed differential analyses on epigenomic, transcriptomic and plasma proteomic data collected from obese individuals before and six months after bariatric surgery. These analyses revealed a pattern of abnormal activation of immune cells in obese individuals and lipodystrophy patients, which was partially reverted six months after bariatric surgery.

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Section: Effect Of Bariatric Surgerysupporting

confidence: 66%

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Seyres¹,

Cabassi

Lambourne³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…After identifying proteins correlating with the established liver damage marker ALT by the global correlation map, we asked if we could reproduce these correlations in our very recently published study on the effect of bariatric surgery in morbidly obese individuals on the plasma proteome (Wewer Albrechtsen et al , ). Correlating protein levels with clinically determined ALT levels across 175 plasma samples confirmed that ALDOB, PIGR, and ANPEP are statistically significantly correlated, whereas TGFBI is very close to the threshold (Fig EV3; Dataset EV2).…”

Section: Resultsmentioning

confidence: 99%

“…This dataset has been published in Wewer Albrechtsen et al () as described in the main text. Red color‐coded proteins are significant.…”

Section: Resultsmentioning

confidence: 99%

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

Niu

Geyer

Albrechtsen

et al. 2019

Molecular Systems Biology

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Non‐alcoholic fatty liver disease ( NAFLD ) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins ( ALDOB , APOM , LGALS 3 BP , PIGR , VTN , and AFM ), two of which are already linked to liver disease. Polymeric immunoglobulin receptor ( PIGR ) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP 4, ANPEP , TGFBI , PIGR , and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP 4 is an aminopeptidase like ANPEP , ENPEP , and LAP 3, all of which are up‐regulated 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.

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“…In our example, six of the eight significant outliers were from the platelet panel, and the other two proteins -GP1BA and NRP1could still be of interest. To investigate this further, we inspected the global correlation map of all proteins, time points and participants (25). In this hierarchical clustering analysis, proteins that are co-regulated have a high correlation to each other and appear in groups, visualized as red patches (Fig.…”

Section: Application Of the Contamination Marker Panels To A Biomarkementioning

confidence: 99%

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

Geyer

Voytik

Treit

et al. 2018

Preprint

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Plasma and serum are rich sources of information regarding an individual's health state and protein tests inform medical decision making. Despite major investments, few new biomarkers have reached the clinic. 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 contamination marker panels to assess plasma samples and the likelihood that suggested biomarkers are instead artifacts related to sample handling and processing. We acquire deep reference proteomes of erythrocytes, platelets, plasma and whole blood of 20 individuals (>6000 proteins), and compare serum and plasma proteomes. Based on spike-in experiments we determine contamination-associated proteins, many of which have been reported as biomarker candidates as revealed by a comprehensive literature survey. We provide sample preparation guidelines and an online resource (www.plasmaproteomeprofiling.org) to assess overall sample-related bias in clinical studies and to prevent costly miss-assignment of biomarker candidates.

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Plasma Proteome Profiling Reveals Dynamics of Inflammatory and Lipid Homeostasis Markers after Roux-En-Y Gastric Bypass Surgery

Cited by 84 publications

References 49 publications

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

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

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

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