生物工学会誌第 95 巻第 5 号 Cytoscape Cytoscape Cytoscape 1) 15 Cytoscape Web 2) Mac Windows Linux OS Cytoscape GML BioPAX PSI-MI KGML SBML Pathway Commons IntAct BioMart Igraph Bioconductor PDF PS SVG PNG JPEG Apps 2017 1 25 Cytoscape 3.4.0 Cytoscape RNA-seq Differentially Expressed Genes: DEGs PPI GRN DEGs 1Cytoscape 1 284 E-mail: kushida@biosciencedbc.jp 95
Cytoscape PPI GRN Cytoscape stringapp 3) GeneMANIA 4) WikiPathways 5) MCDS 6) NetworkAnalyzer 7) Cytoscape Cytoscape Cytoscape Cytoscape Cytoscape(.exe) 2 2File Open Import Cytoscape sampledata galfiltered.cys galfiltered.cys 2 Cytoscape cys Cytoscape File Open Microsoft xls sif gml csv galfiltered.xlsfile > Import > Network > File PPI galexpdata. csv File > Import > Table > File Entrez Gene ID TV Cytoscape 8) File Save cys File > Export > Network Network and View sif xgmml File > Export > Network View as Graphics PDF PS SVG PNG JPEG Apps Cytoscape 170 2017 1 25 Cytoscape Apps > App Manager Apps DEGs 2Network 2 Fold Change DEGs 2 DEGsDEGs Select > Nodes > First Neighbors of Selected Nodes > Undirected 20175 285
File > New > Network > From selected nodes, all edges Network Cytoscape Cytoscape. vmoptions Cytoscape 9) Cytoscape. vmoptions Xmx 4GB Cytoscape Memory 2 Cytoscape Web RNA-seq 1 DEGs DEGs 2 DEGs DEGs 3 DEGs DEGs Cytoscape 1-1 DEGs DEGs Web NetworkAnalyst 10) R Web R 11) R 12) Excel DEGs t-fold Change 1-2 DEGsEnrichment DEGsGene Ontology KEGG Reactome Enrichment Enrichment Web DAVID 13) GSEA 14) Enrichr 15) Cytoscape BiNGO 16) 1-2-1 BiNGO Gene Ontology Gene Ontology DEGs Entrez Gene ID 856571 854106 855005 1 17) over and under expd genesover-expressed genes Apps > BiNGO BiNGO Settings Cluster name Paste Genes from Text DEGs & Overrepresentation Visualization Gene Ontology term Select organism/annotation Homo sapiens Start BiNGO 3 Layout 1 17) DEGs mrna processing (GO:0006397) immune system process (GO:0002376) 1-3 DEGs Enrichment 3 BiNGO 286 95
Gene Ontology term Cytoscape ClueGO 18) Kappa score EnrichmentMap 19) DAVID 13) GSEA 14) BiNGO 16) Cytoscape 1-3-1 ClueGO GO KEGG DEGs Entrez Gene ID 856571 854106 855005 2 20) Table 4 Apps ClueGO ClueGO Load Marker List(s) Mus musculusdegs Entrez Gene ID & ClueGO Settings GO BiologicalProcess ClueGO Functional Analysis Start 2 20) DEGs regulation of exocytosis (GO:0017157) protein localization to endoplasmic reticulum (GO:0070972) Protein export (KEGG:03060) protein localization to endoplasmic reticulum Protein export 4 2-1 DEGs NetworkAnalyst 10) Cytoscape stringapp 3) GeneMANIA 4) DEGs BioGrid IntAct InnateDB DEGs DEGs 2-1-1 stringapp PPI DEGs Entrez Gene ID 856571 854106 855005 1 17) over and under expd genesover-expressed genes File > Import > Network > Public DatabasesImport Network from Public DatabasesData Source STRING: protein query Species Homo sapiens 697 DEGs Import Apps > STRING > Expand Network Expand Network Number of nodes to add to network 100 Relayout network OK 1 17) 697 DEGs 789 PPI 5 2-2 Degree Centrality 4 ClueGO 5 stringapp NetworkAnalyzer 20175 287
Betweenness Centrality NetworkAnalyst 10) Cytoscape NetworkAnalyzer 7) 2-2-1 NetworkAnalyzer PPI GRN 2-1-1 stringapp 3) PPI Network Tools > NetworkAnalyzer > Network Analysis > Analyze Network Node Table Degree BetweennessCentrality 1 17) UTY (uniprot: O14607) MYC (uniprot:p01106) 5 NetworkAnalyzer 7) Cytoscape App Manager 3-1 NetworkAnalyst 10) Cytoscape MCODE 21) NetworkAnalyzer 7) jactivemodules 22) 21) BiNGO 16) ClueGO 18) Enrichment Cytoscape MCDS 6) GRN 3-1-1 MCODE PPI GRN 2 20) Table 4stringApp 3) Apps > 6 MCODE MCODE > Open MCODE MCODE Find Clusters in whole network Advanced Option Analyze Current Network Results Panel MCODE 6 BiNGO 16) ClueGO 18) 2 20) Ubc Rps27a 35 12 3-1-2 MCDS PPI GRN PPI GRN 3 23) File > Open 3 23) Apps > MCDS > StartMCDS 3 23) PPI Optimization criterion largest connected component (undirected) GRN largest connected component (directed) Run MCDS dominator connector MCDSMCDS result 3 23) 471 At1g09780 (ipgam1) 93 7 288 95
Cytoscape Cytoscape UCSD 7 MCDS 1 Cytoscape* DEGs NetworkAnalyst 10), R 11,12) DAVID 13), GSEA 14), Enrichr 15) BiNGO* 16) ClueGO* 18), EnrichmentMap* 19) NetworkAnalyst 10), stringapp* 3) GeneMANIA* 4), WikiPathways* 5) NetworkAnalyst 10), NetworkAnalyzer* 7) NetworkAnalyst 10), MCODE* 21) NetworkAnalyzer* 7) jactivemodules* 22) MCDS 6) Cytoscape 1 Cytoscape SNSCytoscape Publication 24) Cytoscape 1 17) 2 20) NetworkAnalyst 10) GSEA 14) Cytoscape Cytoscape 1) Shannon, P. et al.: Genome Res., 13, 2498 (2003). 2) Cytoscape: http://www.cytoscape.org/ (2017/01/25). 3) Szklarczyk, D. et al.: Nucleic Acids Res., 45, D362 (2017). 4) Warde-Farley, D. et al.: Nucleic Acids Res., 38, W214 (2010). 5) Kutmon, M. et al.: F1000Res., 3, 152 (2014). 6) Nazarieh, M. et al.: BMC Syst. Biol., 10, 88 (2016). 7) Doncheva, N. T. et al.: Nat. Protoc., 7, 670 (2012). 8) TV Cytoscape http://doi.org/10.7875/togotv.2015. 064 (2017/01/25). 9) Cytoscape User Manual: http://manual.cytoscape.org/en/ stable/launching_cytoscape.html?highlight=vmoption #overall-memory-size-for-cytoscape (2017/01/25). 10) NetworkAnalyst: http://www.networkanalyst.ca (2017/ 01/25). 11) R http://www.iu.a.u-tokyo.ac.jp/~kadota/r_seq.html (2017/ 01/25). 12) R http://www.iu.a.u-tokyo.ac.jp/~kadota/r.html (2017/01/25). 13) DAVID: https://david.ncifcrf.gov (2017/01/25). 14) GSEA: http://software.broadinstitute.org/gsea/ (2017/01/ 25). 15) Enrichr: http://amp.pharm.mssm.edu/enrichr/ (2017/01/ 25). 16) Maere, S. et al.: Bioinformatics, 21, 3448 (2005). 17) 1 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5125005/ bin/srep37099-s2.xls (2017/01/25). 18) Bindea, G. et al.: Bioinformatics, 25, 1091 (2009). 19) Merico, D. et al.: PLoS One, 5, e13984 (2010). 20) 2 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5112738/ bin/12864_2016_3228_moesm7_esm.xlsx (2017/01/ 25). 21) Bader, G. D. et al.: BMC Bioinformatics, 4, 2 (2003). 22) Ideker, T. et al.: Bioinformatics, 18, S233 (2002). 23) 3 http://netvis.ico2s.org/dev/seednet/seednet_all_samples. cys (2017/01/25). 24) Cytoscape Publications: http://cytoscape-publications. tumblr.com (2017/01/25). 20175 289