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

Antonov, Alexey V.; Schmidt, Esther; Dietmann, Sabine; Krestyaninova, Maria; Hermjakob, Henning

doi:10.1093/nar/gkq482

Cited by 63 publications

(75 citation statements)

References 37 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For GO analyses, we obtained GO annotations of genes from FlyBase and performed hypergeometric tests for enrichment of genes in all GO terms that contained at least 20 genes in the background gene list, which consisted of genes that contained at least one segregating SNP in the DGRP. We identified subnetworks enriched for epistatic genes using the R-spider web server (22). Rspider compiles the global network from KEGG and Reactome and tests for significance of the subnetwork with the maximal number of input genes through a Monte Carlo simulation-based inference (22).…”

Section: Methodsmentioning

confidence: 99%

“…We identified subnetworks enriched for epistatic genes using the R-spider web server (22). Rspider compiles the global network from KEGG and Reactome and tests for significance of the subnetwork with the maximal number of input genes through a Monte Carlo simulation-based inference (22). We considered only the model where epistatic genes were directly connected without any missing nodes.…”

Section: Methodsmentioning

confidence: 99%

“…Second, we assessed whether epistatic genes were enriched for GO terms and found several biologically plausible GO terms significant at FDR < 0.10 for all three traits (Dataset S1, Table S9). Third, we asked if the epistatic genes were overrepresented in the signaling and metabolic pathways from the Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases (22). We found significant enrichment of subnetworks for epistatic genes associated with starvation resistance (P < 0.005) (SI Appendix, Fig.…”

Section: Widespread Epistasis For Snps Associated With Complex Traits Inmentioning

confidence: 99%

See 2 more Smart Citations

Epistasis dominates the genetic architecture of Drosophila quantitative traits

Huang¹,

Richards

Carbone³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

351

390

View full text Add to dashboard Cite

Epistasis-nonlinear genetic interactions between polymorphic loci-is the genetic basis of canalization and speciation, and epistatic interactions can be used to infer genetic networks affecting quantitative traits. However, the role that epistasis plays in the genetic architecture of quantitative traits is controversial. Here, we compared the genetic architecture of three Drosophila life history traits in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and a large outbred, advanced intercross population derived from 40 DGRP lines (Flyland). We assessed allele frequency changes between pools of individuals at the extremes of the distribution for each trait in the Flyland population by deep DNA sequencing. The genetic architecture of all traits was highly polygenic in both analyses. Surprisingly, none of the SNPs associated with the traits in Flyland replicated in the DGRP and vice versa. However, the majority of these SNPs participated in at least one epistatic interaction in the DGRP. Despite apparent additive effects at largely distinct loci in the two populations, the epistatic interactions perturbed common, biologically plausible, and highly connected genetic networks. Our analysis underscores the importance of epistasis as a principal factor that determines variation for quantitative traits and provides a means to uncover genetic networks affecting these traits. Knowledge of epistatic networks will contribute to our understanding of the genetic basis of evolutionarily and clinically important traits and enhance predictive ability at an individualized level in medicine and agriculture.chill coma recovery | genetic interaction networks | genome-wide association studies | startle response | starvation resistance

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Widespread Epistasis For Snps Associated With Complex Traits Inmentioning

confidence: 99%

See 1 more Smart Citation

Epistasis dominates the genetic architecture of Drosophila quantitative traits

Huang¹,

Richards

Carbone³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

351

390

View full text Add to dashboard Cite

show abstract

“…The input list was furthermore analyzed by R spider. 33 The molecular networks inferred by spider tools are profiled according to three different models, named D1, D2, and D3. In model D1 are considered only the direct interactions between proteins list, while in models D2 and D3 are allowed one and two intermediate nodes, respectively.…”

Section: Bioinformatics and Statistical Analysismentioning

confidence: 99%

Profiling Carbonylated Proteins in Heart and Skeletal Muscle Mitochondria from Trained and Untrained Mice

Carpentieri¹,

Gamberi

Modesti

et al. 2016

J. Proteome Res.

View full text Add to dashboard Cite

Understanding the relationship between physical exercise, reactive oxygen species, and skeletal muscle modification is important in order to better identify the benefits or the damages that appropriate or inappropriate exercise can induce. Heart and skeletal muscles have a high density of mitochondria with robust energetic demands, and mitochondria plasticity has an important role in both the cardiovascular system and skeletal muscle responses. The aim of this study was to investigate the influence of regular physical activity on the oxidation profiles of mitochondrial proteins from heart and tibialis anterior muscles. To this end, we used the mouse as animal model. Mice were divided into two groups: untrained and regularly trained. The carbonylated protein pattern was studied by two-dimensional gel electrophoresis followed by Western blot with anti-dinitrophenyl hydrazone antibodies. Mass spectrometry analysis allowed the identification of several different protein oxidation sites, including methionine, cysteine, proline, and leucine residues. A large number of oxidized proteins were found in both untrained and trained animals. Moreover, mitochondria from skeletal muscles and heart showed almost the same carbonylation pattern. Interestingly, exercise training seems to increase the carbonylation level mainly of mitochondrial proteins from skeletal muscle.

show abstract

“…html), and QIAGEN (www.qiagen. com/geneglobe/path ways.aspx) (Salomonis et al, 2007;Antonov et al, 2010). Moreover, PLC signaling pathway-regulated transcription factors (TFs) such as CREB, NFAT, NF-kB, C-JUN, C-FOS, and C-MYC were input into TRED (http://rulai.cshl.edu/cgi-bin/TRED/tred.cgi?process=searchTFGeneForm) and Lymph TF DB (http://www.iupui.edu/ ~tfinterx/activity.php) to identify their downstream target genes in rat (Childress et al, 2007;Jiang et al, 2007), mouse, and human; cell growth-related genes among these downstream targets were identified in the NCBI database.…”

Section: Identification Of Plc Signaling Pathway-and Cell Growth-relamentioning

confidence: 99%

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration

Xu¹,

Geng²,

Zhou³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (E t ) according to their expression profiles. The results showed that the E t values of G protein- coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.

show abstract

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

Cited by 63 publications

References 37 publications

Epistasis dominates the genetic architecture of Drosophila quantitative traits

Epistasis dominates the genetic architecture of Drosophila quantitative traits

Profiling Carbonylated Proteins in Heart and Skeletal Muscle Mitochondria from Trained and Untrained Mice

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration

Contact Info

Product

Resources

About