IntAct App: a Cytoscape application for molecular interaction network visualization and analysis

Ragueneau, Eliot; Shrivastava, Anjali; Morris, John H.; del-Toro, Noemi; Hermjakob, Henning; Porras, Pablo

doi:10.1093/bioinformatics/btab319

Cited by 24 publications

(16 citation statements)

References 8 publications

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“…The human protein-protein interaction network of the human 3CL pro substrates was constructed by using the 101 high-confidence substrates listed in Table 1 as seeds and retrieving all known interactors using the IntAct app (v 0.9.7) (Ragueneau et al, 2021) in Cytoscape v 3.8.2 (Shannon et al, 2003). Then, a filter was applied to retain only human proteins with curated direct interactions or physical associations to the 101 substrates resulting in a network of 2,301 nodes and 2,931 edges.…”

Section: Author Contributionsmentioning

confidence: 99%

Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CLpro substrate degradome

et al. 2021

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The main viral protease (3CL pro ) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL pro by TAILS substrate-targeted N-terminomics. We identify >100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells. Enzyme kinetics and molecular docking simulations of 3CL pro engaging substrates reveal how noncanonical cleavage sites, which diverge from SARS-CoV, guide substrate specificity. Cleaving the interactors of essential effector proteins, effectively stranding them from their binding partners, amplifies the consequences of proteolysis. We show that 3CL pro targets the Hippo pathway, including inactivation of MAP4K5, and key effectors of transcription, mRNA processing, and translation. We demonstrate that Spike glycoprotein directly binds galectin-8, with galectin-8 cleavage disengaging CALCOCO2/NDP52 to decouple antiviral-autophagy. Indeed, in post-mortem COVID-19 lung samples, NDP52 rarely colocalizes with galectin-8, unlike healthy lung cells. The 3CL pro substrate degradome establishes a foundational substrate atlas to accelerate exploration of SARS-CoV-2 pathology and drug design.

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Section: Author Contributionsmentioning

confidence: 99%

Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CLpro substrate degradome

et al. 2021

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“…The PPI network was constructed by using the STRING database 4 with a confidence score > 0.4 ( 4 ). The downloaded results were imported into Cytoscape 3.8.2 ( 22 ) software for further analysis. The top 10 hub genes in the PPI network were screened out by using the cytoHubba plugin.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis

Zhang

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveThe aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis.Materials and methodsThree databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets.ResultsPatients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29]), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28]), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above.ConclusionCML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.

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“…The obtained active components of HLXLD and the potential targets for psoriasis treatment were imported into Cytoscape 3.8.2 [ 13 ] software to draw the drug-compound-target network diagram for visual analysis, in which “node” was used to represent drugs, components, or targets, and “edge” was used to represent the relationship between nodes. The network parameters of each node were analyzed based on the network analyzer and cytoNCA plugins.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Huoluo Xiaoling Dan in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking

Gong

Guo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the mechanism of the action of Huoluo Xiaoling Dan (HLXLD) in the treatment of psoriasis based on network pharmacology and molecular docking. Methods. The main active components and targets of HLXLD were collected from CMSP, and the targets related to psoriasis were collected from GeneCards, OMIM, TTD, DisGeNET, and DrugBank. Drug disease target genes were obtained by Venny tools, drug-component-target networks were constructed and analyzed, and pathway enrichment analysis was performed. AutoDockTools is used to connect the core components and the target, and PyMOL software is used to visualize the results. Results. 126 active components (such as quercetin, luteolin, tanshinone IIA, dihydrotanshinlactone, and beta-sitosterol) and 238 targets of HLXLD were screened out. 1,293 targets of psoriasis were obtained, and 123 drug-disease targets were identified. Key targets included AKT1, TNF, IL6, TP53, VEGFA, JUN, CASP3, IL1B, STAT3, PTGS2, HIF1A, EGF, MYC, EGFR, MMP9, and PPARG. Enrichment analysis showed that 735 GO analysis and 85 KEGG pathways were mainly involved in biological processes such as response to the drug, inflammatory response, gene expression, and cell proliferation and apoptosis, as well as signal pathways such as cancer, TNF, HIF-1, and T cell receptor. Molecular docking showed that there was strong binding activity between the active ingredient and the target protein. Conclusions. HLXLD could treat psoriasis through multicomponents, multitargets, and multipathways, which provides a new theoretical basis for further basic research and clinical application.

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IntAct App: a Cytoscape application for molecular interaction network visualization and analysis

Cited by 24 publications

References 8 publications

Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CLpro substrate degradome

Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CLpro substrate degradome

Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis

Mechanism of Huoluo Xiaoling Dan in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking

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