ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks

Bindea, Gabriela-Luana; Mlecnik, Bernhard; Hackl, Hubert; Charoentong, Pornpimol; Tosolini, Marie; Kirilovsky, Amos; Fridman, Wolf‐Herman; Pagès, Franck; Trajanoski, Zlatko; Galon, Jérôme

doi:10.1093/bioinformatics/btp101

Cited by 5,026 publications

(4,152 citation statements)

References 11 publications

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“…All proteins related to these categories are listed in Table 3. Similar results regarding the GO terms enriched in the differentially expressed proteins were also obtained following data analysis using Cytoscape software 46 (data not shown). In addition and in support of the specificity of this finding, when Panther analysis was performed using 3 randomly picked similar sized protein datasets or the whole dataset of non- In addition, some proteins found to be down-regulated at 3dpi appeared consistently also down-regulated at 30 days post KA injection, as shown in Table 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Sodium-and chloride-dependent GABA transporter 1 (3dpi: 0.53 fold, 30dpi: 0.37 fold).…”

Section: Protein Expression Response During Chronic Phase Of Epilepsysupporting

confidence: 81%

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

Bitsika

Duveau²,

Simon-Areces

et al. 2016

J. Proteome Res.

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Uncovering the molecular mechanisms of Mesial temporal lobe epilepsy (MTLE) is critical to identify therapeutic targets. In this study, we performed global protein expression analysis of a kainic acid (KA) MTLE mouse model at various time-points (1d, 3d, 30d post KA injection -dpi), representing specific stages of the syndrome.High resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination to label-free protein quantification, using three processing approaches for quantification, was applied. Following comparison of KA versus NaCl-injected mice, 22, 53 and 175 proteins were differentially (statistically significant) expressed at 1, 3 and 30dpi respectively, according to all 3 quantification approaches. Selected findings were confirmed by multiple reaction monitoring LC-MS/MS. As a positive control, the astrocyte marker GFAP was found to be upregulated (3dpi:1.9 fold; 30dpi:12.5 fold), also verified by IHC. The results collectively suggest that impairment in synaptic transmission occurs even right after initial status epilepticus (1dpi), with neurodegeneration becoming more extensive during epileptogenesis (3dpi) and sustained at the chronic phase (30dpi), where also extensive glial and astrocyte-mediated inflammation is evident. This molecular profile is in line with observed phenotypic changes in human MTLE, providing the basis for future studies on new molecular targets for the disease.

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Section: Protein Expression Response During Chronic Phase Of Epilepsysupporting

confidence: 81%

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

Bitsika

Duveau²,

Simon-Areces

et al. 2016

J. Proteome Res.

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“…Thus, DM seems to induce some unique and specific effects in T cells independent from the general activation process. To characterise these, we performed a pathway analysis [13]. The mechanisms that were downregulated by DM included TCR signalling pathway, helper T-cell surface molecules, and apoptosis-related mechanisms, which are compatible with findings in Figs.…”

Section: Transcriptomic Characteristics Of Dm-treated T Cellssupporting

confidence: 75%

Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T‐cell activation and differentiation

et al. 2011

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Bone morphogenetic proteins (BMPs) are involved in patterning and cellular fate in various organs including the thymus. However, the redundancy of BMPs and their receptors have made it difficult to analyse their physiological roles. Here, we investigated the role of BMP signalling in peripheral CD4 1 T cells by analysing the effects of an inhibitor of BMP signalling, dorsomorphin. Dorsomorphin suppressed phosphorylation of SMAD1/5/8, suggesting that BMP signalling naturally occurs in T cells. At high doses, dorsomorphin suppressed proliferation of T cells in a dose-dependent manner, inducing G1 arrest. Also, dorsomorphin suppressed Th17 and induced Treg-cell differentiation, while preserving Th2 differentiation. Dorsomorphin efficiently suppressed IL-2 production even at low doses in mouse CD4 1 T cells, suggesting that the BMP-Smad signalling physiologically regulates IL-2 transcription in these cells. In addition, recombinant BMP2 induced a dosedependent multiphasic pattern of IL-2 production, while Noggin suppressed IL-2 production at higher doses in Jurkat cells. Notably, BMP signalling controlled the phosphorylation of RUNX1, revealing the molecular nature of its effect. Collectively, we describe multiple effects of dorsomorphin and Noggin on T-cell activation and differentiation, demonstrating a physiological role for BMP signalling in these processes.

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“…Cufflinks (v2.1.1) was used to estimate the relative abundance of transcripts based on how many reads supported each one, taking into account biases in library preparation protocols. Expression data was statistically analyzed in R. Functional annotation and pathway analysis was carried out using a combination of gProfiler (Reimand et al 2016) and Gene Ontology (Ashburner et al 2000), and KEGG pathways (Kanehisa and Goto 2000;Kanehisa et al 2015) implemented in ClueGO in Cytoscape v3.2 (Bindea et al 2009). A hypergeometric test with Benjamin and Hochberg false discovery rate (FDR) was performed using the default parameters implemented in ClueGO.…”

Section: Data Handling Proceduresmentioning

confidence: 99%

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Srikanth

Kwon

Lee

2017

Cell Stress and Chaperones

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This study aimed to investigate the genes and pathways that respond to heat stress in Holstein bull calves exposed to severe ranges of temperature and humidity. A total of ten animals from 4 to 6 months of age were subjected to heat stress at 37°C and 90 % humidity for 12 h. Skin and rectal temperatures were measured before and after heat stress; while no correlation was found between them before heat stress, a moderate correlation was detected after heat stress, confirming rectal temperature to be a better barometer for monitoring heat stress. RNAseq analysis identified 8567 genes to be differentially regulated, out of which 465 genes were significantly upregulated (≥2-fold, P < 0.05) and 49 genes were significantly downregulated (≤2-fold, P < 0.05) in response to heat stress. Significant terms and pathways enriched in response to heat stress included chaperones, cochaperones, cellular response to heat stress, phosphorylation, kinase activation, immune response, apoptosis, Toll-like receptor signaling pathway, Pi3K/AKT activation, protein processing in endoplasmic reticulum, interferon signaling, pathways in cancer, estrogen signaling pathway, and MAPK signaling pathway. The differentially expressed genes were validated by quantitative realtime PCR analysis, which confirmed the tendency of the expression. The genes and pathways identified in this analysis extend our understanding of transcriptional response to heat stress and their likely functioning in adapting the animal to hyperthermic stress. The identified genes could be used as candidate genes for association studies to select and breed animals with improved heat tolerance.

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ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks

Cited by 5,026 publications

References 11 publications

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T‐cell activation and differentiation

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

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