The Reactome pathway knowledgebase

Croft, David; Fabregat, Antonio; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani V.; Gillespie, Marc; Kamdar, Maulik R.; Jassal, Bijay; Jupe, S; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D’Eustachio, Peter

doi:10.1093/nar/gkt1102

Cited by 1,452 publications

(1,259 citation statements)

References 27 publications

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“…3b). Further downstream analysis through the Reactome (Croft et al, 2014) suggests that the pathway G alpha (i) signaling events (p-Value 9.37 × 10 −3 ) is potentially affected by DE down regulated genes and thus inactive. We also enriched this dataset for Biological process and Molecular function with Gorilla.…”

Section: General Overview Of the Whole Transcriptome Sequencingmentioning

confidence: 99%

RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain

Côrtes

Cao

Liu

et al. 2017

Journal of Neuroscience Methods

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Background-The chronically instrumented fetal sheep is a widely used animal model to study fetal brain development in health and disease, but no methods exist yet to interrogate dedicated brain cell populations to identify their molecular and genomic phenotype. For example, the molecular mechanisms whereby microglia or astrocytes contribute to inflammation in the brain remain incompletely understood.New method-Here we present a protocol to derive primary pure microglial or astrocyte cultures from near-term fetal sheep brain, after the animals have been chronically instrumented and studied in vivo. Next, we present the implementation of whole transcriptome sequencing (RNAseq) pipeline to deeper elucidate the phenotype of such primary sheep brain glial cultures. Results-We CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptConclusions-The presented approach opens new possibilities for testing not only supernatant protein levels in response to an in vitro challenge, but also to evaluate changes in the transcriptome of glial cells derived from a large mammalian brain bearing high resemblance to the human brain. Moreover, the presented approach lends itself to modeling the complex multi-hit paradigms of antenatal and perinatal cerebral insults in vivo and in vitro.

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Section: General Overview Of the Whole Transcriptome Sequencingmentioning

confidence: 99%

RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain

Côrtes

Cao

Liu

et al. 2017

Journal of Neuroscience Methods

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“…Link Content NCBI Gene [66] www.ncbi.nlm.nih.gov/gene Atlas of 59,500 human genes GOA [67] www.ebi.ac.uk/GOA 487,409 Gene Ontology annotations for 48,569 human gene products ENCODE [68] www.encodeproject.org Functional annotations of coding/non-coding DNA elements NCBI Epigenomics [69] www.ncbi.nlm.nih.gov/epigenomics 5,110 epigenetic modifications 4DGenome [70] 4dgenome [73] www.ebi.ac.uk/gxa Differential and baseline gene expression data CMAP [74] www.broadinstitute.org/cmap ∼ 7,000 expression profiles for 1,309 perturbagen compounds COXPRESdb [75] coxpresdb.jp Co-expression of 19,803 human genes GeneFriends [76] genefriends.org Co-expression of 159,184 human genes and transcripts UniProt [77] www.uniprot.org Information about human proteome (69,693 proteins) NeXtProt [78] www.nextprot.org Knowledgebase on 20,066 human proteins RCSB PDB [79] www.rcsb.org/pdb Portal to 113,494 biological macromolecular 3D-structures HPA [80] www.thehpp.org Maps of human proteome on 44 normal and 20 cancer type tissues IntAct [81] www.ebi.ac.uk/intact 209,852 human protein-protein interactions BioGrid [82] thebiogrid.org 215,952 human protein-protein interactions I2D [83] ophid.utoronto.ca 183,524 (+ 55,985 predicted) protein-protein interactions STRING [84] string-db.org 8,548,005 interactions between 20,457 proteins HMDB [85] www.hmdb.ca Atlas of 41,993 human metabolites KEGG Pathway [86] www.genome.jp/kegg/pathway 298 human pathways SMPD [87] www.smpdb.ca ∼700 human metabolic and disease pathways Reactome [88] www.reactome.org 8,770 reactions in 1,887 human pathways SugarBindDB [89] sugarbind.expasy.org 1,256 interactions between 200 glycans and 551 pathogenic agents UniCarbKB [90] www.unicarbkb.org 3,740 glycan structure entries and 400 glycoproteins KEGG Glycan [91] www.genome.jp/kegg/glycan/ Glycan metabolic pathways OMIM [92] www.omim.org Catalog of mendelian disorders and over 15,000 genes NCBI dbGaP [93] www.ncbi.nlm.nih.gov/gap Database of genotypes and phenotypes GWAS Catalog [94] www.ebi.ac.uk/gwas/ Genome wide association studies, assaying ∼ 100,000 SNPs COSMIC...…”

Section: Databasementioning

confidence: 99%

Integrative methods for analyzing big data in precision medicine

2016

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We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of Big Data in biology and medicine. These data offer many opportunities to advance precision medicine.We outline key challenges in precision medicine and present recent advances in data integrationbased methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, bio-markers discovery and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face.

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“…reactome.org) (Croft et al, 2014) is a curated, peer-reviewed resource of human biological pathways and reaction network. The presumed inherited direction (PID) (Schaefer et al, 2009), a pathway interaction database, mainly focus on signaling pathways.…”

Section: Functional Enrichment Analysesmentioning

confidence: 99%

Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction

Zhou

Zhang

et al. 2017

Brain and Behavior

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Introduction We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction ( MMI ) and elucidate their underlying regulatory mechanisms. Methods We first developed a cytokine profile by Quantibody ® Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non‐acute cerebral infarction ( NACI ). The differentially expressed cytokines were then identified in patients with MMI using two‐tailed Student's t ‐test and Fisher's Exact Test compared with patients with NACI . Gene Ontology and pathway enrichment analyses were performed using DAVID . Protein–protein interaction ( PPI ) network was constructed based on STRING database. Results A total of 10 differentially expressed cytokines were identified from 320 unique inflammatory cytokines in serums. Among them, four cytokines, like NCAM 1 (neural cell adhesion molecule 1), IGFBP ‐6 (insulin‐like growth factor binding protein 6), LYVE 1 (lymphatic vessel endothelial hyaluronan receptor 1), and LCN 2 (Lipocalin2), were up‐regulated, while another six cytokines, such as TGFB 1 (transforming growth factor, beta 1, also known as LAP ), EGF (epidermal growth factor), PDGFA (platelet‐derived growth factor alpha polypeptide), MMP ‐10 (matrix metallopeptidase 10), IL ‐27 (interleukin 27), and CCL 2 (chemokine (C‐C motif) receptor 2), were down‐regulated. Moreover, cytokine–cytokine receptor interaction pathway was significantly enriched. Conclusions Our findings indicate that 10 differentially expressed cytokines, such as NCAM 1, LCN 2, IGFBP‐6, LYVE1, MMP‐10, IL‐27, PDGFA , EGF , CCL 2, and TGFB 1 may participate in the development of MMI . Moreover, cytokine–cytokine receptor interaction pathway may be an important mechanism involved in this disease. These differentially expressed cytokines may serve as diagnostic biomarkers or drug targets for MMI .

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The Reactome pathway knowledgebase

Cited by 1,452 publications

References 27 publications

RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain

RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain

Integrative methods for analyzing big data in precision medicine

Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction

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