CyTargetLinker: A Cytoscape App to Integrate Regulatory Interactions in Network Analysis

被引:90
作者
Kutmon, Martina [1 ,2 ]
Kelder, Thomas [3 ]
Mandaviya, Pooja [1 ]
Evelo, Chris T. A. [1 ,2 ]
Coort, Susan L. [1 ]
机构
[1] Univ Maastricht, Dept Bioinformat BiGCaT, NUTRIM Sch Nutr Toxicol & Metab, Maastricht, Netherlands
[2] Netherlands Consortium Syst Biol NCSB, Amsterdam, Netherlands
[3] TNO, Res Grp Microbiol & Syst Biol, NL-3700 AJ Zeist, Netherlands
来源
PLOS ONE | 2013年 / 8卷 / 12期
关键词
GENE; INSIGHTS;
D O I
10.1371/journal.pone.0082160
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Introduction: The high complexity and dynamic nature of the regulation of gene expression, protein synthesis, and protein activity pose a challenge to fully understand the cellular machinery. By deciphering the role of important players, including transcription factors, microRNAs, or small molecules, a better understanding of key regulatory processes can be obtained. Various databases contain information on the interactions of regulators with their targets for different organisms, data recently being extended with the results of the ENCODE (Encyclopedia of DNA Elements) project. A systems biology approach integrating our understanding on different regulators is essential in interpreting the regulation of molecular biological processes. Implementation: We developed CyTargetLinker (http://projects.bigcat.unimaas.nl/cytargetlinker), a Cytoscape app, for integrating regulatory interactions in network analysis. Recently we released CyTargetLinker as one of the first apps for Cytoscape 3. It provides a user-friendly and flexible interface to extend biological networks with regulatory interactions, such as microRNA-target, transcription factor-target and/or drug-target. Importantly, CyTargetLinker employs identifier mapping to combine various interaction data resources that use different types of identifiers. Results: Three case studies demonstrate the strength and broad applicability of CyTargetLinker, (i) extending a mouse molecular interaction network, containing genes linked to diabetes mellitus, with validated and predicted microRNAs, (ii) enriching a molecular interaction network, containing DNA repair genes, with ENCODE transcription factor and (iii) building a regulatory meta-network in which a biological process is extended with information on transcription factor, microRNA and drug regulation. Conclusions: CyTargetLinker provides a simple and extensible framework for biologists and bioinformaticians to integrate different regulatory interactions into their network analysis approaches. Visualization options enable biological interpretation of complex regulatory networks in a graphical way. Importantly the incorporation of our tool into the Cytoscape framework allows the application of CyTargetLinker in combination with a wide variety of other apps for state-of-the-art network analysis.
引用
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页数:9
相关论文
共 29 条
[1]  
Ade Alex., 2007, Gene2MeSH
[2]  
[Anonymous], J ONCOL
[3]   Reorganizing the protein space at the Universal Protein Resource (UniProt) [J].
Apweiler, Rolf ;
Martin, Maria Jesus ;
O'Donovan, Claire ;
Magrane, Michele ;
Alam-Faruque, Yasmin ;
Antunes, Ricardo ;
Casanova, Elisabet Barrera ;
Bely, Benoit ;
Bingley, Mark ;
Bower, Lawrence ;
Bursteinas, Borisas ;
Chan, Wei Mun ;
Chavali, Gayatri ;
Da Silva, Alan ;
Dimmer, Emily ;
Eberhardt, Ruth ;
Fazzini, Francesco ;
Fedotov, Alexander ;
Garavelli, John ;
Castro, Leyla Garcia ;
Gardner, Michael ;
Hieta, Reija ;
Huntley, Rachael ;
Jacobsen, Julius ;
Legge, Duncan ;
Liu, Wudong ;
Luo, Jie ;
Orchard, Sandra ;
Patient, Samuel ;
Pichler, Klemens ;
Poggioli, Diego ;
Pontikos, Nikolas ;
Pundir, Sangya ;
Rosanoff, Steven ;
Sawford, Tony ;
Sehra, Harminder ;
Turner, Edward ;
Wardell, Tony ;
Watkins, Xavier ;
Corbett, Matt ;
Donnelly, Mike ;
van Rensburg, Pieter ;
Goujon, Mickael ;
McWilliam, Hamish ;
Lopez, Rodrigo ;
Xenarios, Ioannis ;
Bougueleret, Lydie ;
Bridge, Alan ;
Poux, Sylvain ;
Redaschi, Nicole .
NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) :D71-D75
[4]   BioNetBuilder: automatic integration of biological networks [J].
Avila-Campillo, Iliana ;
Drew, Kevin ;
Lin, John ;
Reiss, David J. ;
Bonneau, Richard .
BIOINFORMATICS, 2007, 23 (03) :392-393
[5]  
Bentley DR, 2000, MED RES REV, V20, P189, DOI 10.1002/(SICI)1098-1128(200005)20:3<189::AID-MED2>3.0.CO
[6]  
2-#
[7]   CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data [J].
Bindea, Gabriela ;
Galon, Jerome ;
Mlecnik, Bernhard .
BIOINFORMATICS, 2013, 29 (05) :661-663
[8]   ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks [J].
Bindea, Gabriela ;
Mlecnik, Bernhard ;
Hackl, Hubert ;
Charoentong, Pornpimol ;
Tosolini, Marie ;
Kirilovsky, Amos ;
Fridman, Wolf-Herman ;
Pages, Franck ;
Trajanoski, Zlatko ;
Galon, Jerome .
BIOINFORMATICS, 2009, 25 (08) :1091-1093
[9]   Reactome: a database of reactions, pathways and biological processes [J].
Croft, David ;
O'Kelly, Gavin ;
Wu, Guanming ;
Haw, Robin ;
Gillespie, Marc ;
Matthews, Lisa ;
Caudy, Michael ;
Garapati, Phani ;
Gopinath, Gopal ;
Jassal, Bijay ;
Jupe, Steven ;
Kalatskaya, Irina ;
Mahajan, Shahana ;
May, Bruce ;
Ndegwa, Nelson ;
Schmidt, Esther ;
Shamovsky, Veronica ;
Yung, Christina ;
Birney, Ewan ;
Hermjakob, Henning ;
D'Eustachio, Peter ;
Stein, Lincoln .
NUCLEIC ACIDS RESEARCH, 2011, 39 :D691-D697
[10]   An integrated encyclopedia of DNA elements in the human genome [J].
Dunham, Ian ;
Kundaje, Anshul ;
Aldred, Shelley F. ;
Collins, Patrick J. ;
Davis, CarrieA. ;
Doyle, Francis ;
Epstein, Charles B. ;
Frietze, Seth ;
Harrow, Jennifer ;
Kaul, Rajinder ;
Khatun, Jainab ;
Lajoie, Bryan R. ;
Landt, Stephen G. ;
Lee, Bum-Kyu ;
Pauli, Florencia ;
Rosenbloom, Kate R. ;
Sabo, Peter ;
Safi, Alexias ;
Sanyal, Amartya ;
Shoresh, Noam ;
Simon, Jeremy M. ;
Song, Lingyun ;
Trinklein, Nathan D. ;
Altshuler, Robert C. ;
Birney, Ewan ;
Brown, James B. ;
Cheng, Chao ;
Djebali, Sarah ;
Dong, Xianjun ;
Dunham, Ian ;
Ernst, Jason ;
Furey, Terrence S. ;
Gerstein, Mark ;
Giardine, Belinda ;
Greven, Melissa ;
Hardison, Ross C. ;
Harris, Robert S. ;
Herrero, Javier ;
Hoffman, Michael M. ;
Iyer, Sowmya ;
Kellis, Manolis ;
Khatun, Jainab ;
Kheradpour, Pouya ;
Kundaje, Anshul ;
Lassmann, Timo ;
Li, Qunhua ;
Lin, Xinying ;
Marinov, Georgi K. ;
Merkel, Angelika ;
Mortazavi, Ali .
NATURE, 2012, 489 (7414) :57-74