R spider: a network-based analysis of gene lists by combining signaling and metabolic pathways from Reactome and KEGG databases

Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Institute for Bioinformatics and Systems Biology, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
Nucleic Acids Research (Impact Factor: 9.11). 07/2010; 38(Web Server issue):W78-83. DOI: 10.1093/nar/gkq482
Source: PubMed


R spider is a web-based tool for the analysis of a gene list using the systematic knowledge of core pathways and reactions in human biology accumulated in the Reactome and KEGG databases. R spider implements a network-based statistical framework, which provides a global understanding of gene relations in the supplied gene list, and fully exploits the Reactome and KEGG knowledge bases. R spider provides a user-friendly dialog-driven web interface for several model organisms and supports most available gene identifiers. R spider is freely available at

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Available from: Sabine Dietmann, Oct 01, 2015
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    • "These GO categories were highly enriched for genes involved in the development of the nervous system. Next, we performed pathway enrichment analyses for the candidate genes identified as top associations in the GWA analyses using the R-spider algorithm (Antonov et al. 2010), which combines information from the Reactome and KEGG databases to build interactive networks, while determining whether interactions between gene products are greater than expected by chance. We first considered the 645 genes that contained at least one DNA variant showing associations "
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    ABSTRACT: The genetic underpinnings that contribute to variation in olfactory perception are not fully understood. To explore the genetic basis of variation in olfactory perception, we measured behavioral responses to 14 chemically diverse naturally occurring odorants in 260400 flies from 186 lines of the Drosophila melanogaster Genetic Reference Panel, a population of inbred wild-derived lines with sequenced genomes. We observed variation in olfactory behavior for all odorants. Low to moderate broad-sense heritabilities and the large number of tests for genotype-olfactory phenotype association performed precluded any individual variant from reaching formal significance. However, the top variants (nominal P < 5×10(-5)) were highly enriched for genes involved in nervous system development and function, as expected for a behavioral trait. Further, pathway enrichment analyses showed that genes tagged by the top variants included components of networks centered on cyclic guanosine monophosphate and inositol triphosphate signaling, growth factor signaling, Rho signaling, axon guidance, and regulation of neural connectivity. Functional validation with RNAi and mutations showed that 15 out of 17 genes tested indeed affect olfactory behavior. Our results show that in addition to chemoreceptors, variation in olfactory perception depends on polymorphisms that can result in subtle variations in synaptic connectivity within the nervous system. © The Author 2015. Published by Oxford University Press.
    Chemical Senses 02/2015; 40(4). DOI:10.1093/chemse/bjv001 · 3.16 Impact Factor
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    • "The p-value provided, computed by Monte Carlo simulation (, refers to the probability to get a model of the same quality for a random gene list of the same size (Antonov et al., 2010). "
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    ABSTRACT: Parkinson's disease (PD) is a complex neurodegenerative disease whose etiology has not been completely characterized. Many cellular processes have been proposed to play a role in the neuronal damage and loss: defects in the proteosomal activity, altered protein processing, increased reactive oxygen species burden. Among them, the involvement of a decreased activity and an altered disposal of mitochondria is becoming more and more evident. The mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP +), an inhibitor of complex I, has been widely used to reproduce biochemical alterations linked to PD in vitro and its precursor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), to induce a Parkinson-like syndrome in vivo. Therefore, we performed a meta-analysis of the literature of all the proteomic investigations of neuronal alterations due to MPP + treatment and compared it with our results obtained with a mitochondrial proteomic analysis of SH-SY5Y cells treated with MPP + . By using open-source bioinformatics tools, we identified the biochemical pathways and the molecular functions mostly affected by MPP + , i.e., ATP production, the mitochondrial unfolded stress response, apoptosis, autophagy, and, most importantly, the synapse funcionality. Eventually, we generated protein networks, based on physical or functional interactions, to highlight the relationships among the molecular actors involved. In particular, we identified the mitochondrial protein HSP60 as the central hub in the protein-protein interaction network. As a whole, this analysis clarified the cellular responses to MPP + , the specific mitochondrial proteome alterations induced and how this toxic model can recapitulate some pathogenetic events of PD.
    Frontiers in Cellular Neuroscience 02/2015; 9. DOI:10.3389/fncel.2015.00014 · 4.29 Impact Factor
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    • "The first group [ProfCom (17), PLIPS (12), CCancer (13), GeneSet2MiRNA (18)] employs a modified enrichment analyses schema (19). The second group [KEGG spider (20), R spider (21), PPI spider (22)] implements a novel statistical methodology for the network-based interpretation of a gene list. Finally, GeneSet2MiRNA provides statistical information whether or not a query gene list has a signature of miRNA regulatory activity. "
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    ABSTRACT: The Munich Information Center for Protein Sequences (MIPS at the Helmholtz Center for Environmental Health, Neuherberg, Germany) has many years of experience in providing annotated collections of biological data. Selected data sets of high relevance, such as model genomes, are subjected to careful manual curation, while the bulk of high-throughput data is annotated by automatic means. High-quality reference resources developed in the past and still actively maintained include Saccharomyces cerevisiae, Neurospora crassa and Arabidopsis thaliana genome databases as well as several protein interaction data sets (MPACT, MPPI and CORUM). More recent projects are PhenomiR, the database on microRNA-related phenotypes, and MIPS PlantsDB for integrative and comparative plant genome research. The interlinked resources SIMAP and PEDANT provide homology relationships as well as up-to-date and consistent annotation for 38,000,000 protein sequences. PPLIPS and CCancer are versatile tools for proteomics and functional genomics interfacing to a database of compilations from gene lists extracted from literature. A novel literature-mining tool, EXCERBT, gives access to structured information on classified relations between genes, proteins, phenotypes and diseases extracted from Medline abstracts by semantic analysis. All databases described here, as well as the detailed descriptions of our projects can be accessed through the MIPS WWW server (
    Nucleic Acids Research 01/2011; 39(Database issue):D220-4. DOI:10.1093/nar/gkq1157 · 9.11 Impact Factor
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