Visualize omics data on networks with Omics Visualizer, a Cytoscape App

Legeay, Marc; Doncheva, Nadezhda T.; Morris, John H.; Jensen, Lars Juhl

doi:10.12688/f1000research.22280.1

Cited by 65 publications

(26 citation statements)

References 11 publications

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“…Gene Ontology (GO) term sorting is performed by combining strength and number of input proteins retrieved for the term. Omics visualizer app ( 22 ) is used to show biologically relevant terms. For the other comparative analyses, two-tailed t-test and ANOVA test were used.…”

Section: Methodsmentioning

confidence: 99%

Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

et al. 2022

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Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

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Section: Methodsmentioning

confidence: 99%

Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

et al. 2022

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“…Subclusters of highly interconnected proteins were generated with MCODE (default settings) and functional enrichment was obtained from STRING with the human proteome as background. The dynamics of individual Ub sites in response to MG132 and PR619 were visualised on each node using the Omics Visualizer app (1.3.0) for Cytoscape (3.8.2) 83 . A network including PARP1 was generated in the same manner but with a STRING confidence cutoff at 0.7.…”

Section: Methodsmentioning

confidence: 99%

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates

et al. 2022

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The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhibitors and mass spectrometry. We uncover large dynamic ubiquitin signalling networks with substrates and sites preferentially regulated by DUBs or by the proteasome, highlighting the role of DUBs in degradation-independent ubiquitination. DUBs regulate substrates via at least 40,000 unique sites. Regulated networks of ubiquitin substrates are involved in autophagy, apoptosis, genome integrity, telomere integrity, cell cycle progression, mitochondrial function, vesicle transport, signal transduction, transcription, pre-mRNA splicing and many other cellular processes. Moreover, we show that ubiquitin conjugated to SUMO2/3 forms a strong proteasomal degradation signal. Interestingly, PARP1 is hyper-ubiquitinated in response to DUB inhibition, which increases its enzymatic activity. Our study uncovers key regulatory roles of DUBs and provides a resource of endogenous ubiquitination sites to aid the analysis of substrate specific ubiquitin signalling.

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“…Functional interaction networks were built using stringApp (v 1.4.2) in Cytoscape (v 3.6.1), which includes both physical interactions from experimental data and functional associations from curated pathways, automatic text mining, and prediction methods; with a confidence score cutoff of 0.4 [ 7 ]. Finally, transcriptomic data were assembled into a functional network using Omics Visualizer (v 1.3.0) in Cytoscape (3.8.1) [ 8 ]. To avoid inference of interdependence between gene expression levels and their functional links, the edges from the networks including transcriptomic data were removed.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress

2020

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Chronic exposure of β-cells to nutrient-rich metabolic stress impairs mitochondrial metabolism and its coupling to insulin secretion. We exposed isolated human islets to different metabolic stresses for 3 days: 0.4 mM oleate or 0.4 mM palmitate at physiological 5.5 mM glucose (lipotoxicity), high 25 mM glucose (glucotoxicity), and high 25 mM glucose combined with 0.4 mM oleate and/or palmitate (glucolipotoxicity). Then, we profiled the mitochondrial carriers and associated genes with RNA-Seq. Diabetogenic conditions, and in particular glucotoxicity, increased expression of several mitochondrial solute carriers in human islets, such as the malate carrier DIC, the α-ketoglutarate-malate exchanger OGC, and the glutamate carrier GC1. Glucotoxicity also induced a general upregulation of the electron transport chain machinery, while palmitate largely counteracted this effect. Expression of different components of the TOM/TIM mitochondrial protein import system was increased by glucotoxicity, whereas glucolipotoxicity strongly upregulated its receptor subunit TOM70. Expression of the mitochondrial calcium uniporter MCU was essentially preserved by metabolic stresses. However, glucotoxicity altered expression of regulatory elements of calcium influx as well as the Na+/Ca2+ exchanger NCLX, which mediates calcium efflux. Overall, the expression profile of mitochondrial carriers and associated genes was modified by the different metabolic stresses exhibiting nutrient-specific signatures.

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Visualize omics data on networks with Omics Visualizer, a Cytoscape App

Cited by 65 publications

References 11 publications

Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates

Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress

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