Using VisANT to Analyze Networks

Zhenjun Hu1

1 Bioinformatics Program, Boston University, Boston, Massachusetts
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.8
DOI:  10.1002/0471250953.bi0808s45
Online Posting Date:  March, 2014
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


VisANT is a Web‐based workbench for the integrative analysis of biological networks that offers unique features such as exploratory navigation of interaction network and multi‐scale visualization and inference with integrated hierarchical knowledge. It provides functionalities for convenient construction, visualization, and analysis of molecular and higher‐order networks based on functional (e.g., expression profiles, phylogenetic profiles) and physical (e.g., yeast two‐hybrid, chromatin‐immunoprecipitation, and drug target) relations from either the Predictome database or user‐defined data sets. Analysis capabilities include network structure analysis, over‐representation analysis, expression enrichment analysis, etc. Additionally, networks can be saved, accessed, and shared online. VisANT is able to develop and display meta‐networks for meta‐nodes that are structural complexes, pathways, or any kind of sub‐networks. Further, VisANT supports a growing number of standard exchange formats and database‐referencing standards, e.g., PSI‐MI, KGML, BioPAX, and SBML (in progress). Multiple species are supported to the extent that interactions or associations are available (i.e., public datasets or Predictome database). Curr. Protoc. Bioinform. 45:8.8.1‐8.8.39. © 2014 by John Wiley & Sons, Inc.

Keywords: interaction; network; meta‐network; visualization; integration

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Basic Network Construction
  • Alternate Protocol 1: Constructing and Comparing Large‐Scale Networks
  • Support Protocol 1: Quantitative Characteristics of Network Topologies
  • Support Protocol 2: Online Saving and Reading of the Network
  • Support Protocol 3: Customizing Visual Properties of the Network
  • Support Protocol 4: Using Batch Mode and Macros
  • Basic Protocol 2: Analyzing the Biological Network
  • Basic Protocol 3: Connecting Genes, Drugs, Diseases, and Therapies: An Application to Drug Repositioning
  • Commentary
  • Figures
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
  Ashburn, T.T. and Thor, K.B. 2004. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug. Discov. 3:673‐683.
  Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., Harris, M.A., Hill, D.P., Issel‐Tarver, L., Kasarskis, A., Lewis, S., Matese, J.C., Richardson, J.E., Ringwald, M., Rubin, G.M., and Sherlock, G. 2000. Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25:25‐29.
  Barabasi, A.L., Gulbahce, N., and Loscalzo, J. 2011. Network medicine: A network‐based approach to human disease. Nat. Rev. Genet. 12:56‐68.
  Bast, R.C. Jr. 2011. Molecular approaches to personalizing management of ovarian cancer. Ann. Oncol. 22:viii5‐viii15.
  Becker, K.G., Barnes, K.C., Bright, T.J., and Wang, S.A. 2004. The genetic association database. Nat. Genet. 36:431‐432.
  Benson, D.A., Clark, K., Karsch‐Mizrachi, I., Lipman, D.J., Ostell, J., and Sayers, E.W. 2014. GenBank. Nucleic Acids Res 42:D32‐D37.
  Borisy, A.A., Elliott, P.J., Hurst, N.W., Lee, M.S., Lehar, J., Price, E.R., Serbedzija, G., Zimmermann, G.R., Foley, M.A., Stockwell, B.R., and Keith, C.T. 2003. Systematic discovery of multicomponent therapeutics. Proc. Natl. Acad. Sci. U.S.A. 100:7977‐7982.
  Chatr‐Aryamontri, A., Breitkreutz, B.J., Heinicke, S., Boucher, L., Winter, A., Stark, C., Nixon, J., Ramage, L., Kolas, N., O'Donnell, L., Reguly, T., Breitkreutz, A., Sellam, A., Chen, D., Chang, C., Rust, J., Livstone, M., Oughtred, R., Dolinski, K., and Tyers, M. 2013. The BioGRID interaction database: 2013 update. Nucleic Acids Res. 41:D816‐D823.
  Chavali, S., Barrenas, F., Kanduri, K., and Benson, M. 2010. Network properties of human disease genes with pleiotropic effects. BMC Syst. Biol. 4:78.
  Corbett, A., Pickett, J., Burns, A., Corcoran, J., Dunnett, S.B., Edison, P., Hagan, J.J., Holmes, C., Jones, E., Katona, C., Kearns, I., Kehoe, P., Mudher, A., Passmore, A., Shepherd, N., Walsh, F., and Ballard, C. 2012. Drug repositioning for Alzheimer's disease. Nat. Rev. Drug. Discov. 11:833‐846.
  Costanzo, M.C., Engel, S.R., Wong, E.D., Lloyd, P., Karra, K., Chan, E.T., Weng, S., Paskov, K.M., Roe, G.R., Binkley, G., Hitz, B.C., and Cherry, J.M. 2014. Saccharomyces genome database provides new regulation data. Nucleic Acids Res. 42:D717‐D725.
  Csermely, P., Agoston, V., and Pongor, S. 2005. The efficiency of multi‐target drugs: The network approach might help drug design. Trends Pharmacol. Sci. 26:178‐182.
  Drysdale, R. 2008. FlyBase: A database for the Drosophila research community. Methods Mol. Biol. 420:45‐59.
  Goh, K.I., Cusick, M.E., Valle, D., Childs, B., Vidal, M., and Barabasi, A.L. 2007. The human disease network. Proc. Natl. Acad. Sci. U.S.A. 104:8685‐8690.
  Harrison, C. 2011. Signatures for drug repositioning. Nat. Rev. Genet. 12:668.
  Hermjakob, H., Montecchi‐Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Ceol, A., Moore, S., Orchard, S., Sarkans, U., von Mering, C., Roechert, B., Poux, S., et al., 2004. The HUPO PSI's molecular interaction format: A community standard for the representation of protein interaction data. Nat. Biotechnol. 22:177‐183.
  Hopkins, A.L. 2008. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol. 4:682‐690.
  Hu, Z., Mellor, J., Wu, J., and DeLisi, C. 2004. VisANT: An online visualization and analysis tool for biological interaction data. BMC Bioinformatics 5:17.
  Hu, Z., Mellor, J., Wu, J., Yamada, T., Holloway, D., and Delisi, C. 2005. VisANT: Data‐integrating visual framework for biological networks and modules. Nucleic Acids Res. 33:W352‐W357.
  Hu, Z., Mellor, J., Wu, J., Kanehisa, M., Stuart, J.M., and DeLisi, C. 2007a. Towards zoomable multidimensional maps of the cell. Nat. Biotechnol. 25:547‐554.
  Hu, Z., Ng, D.M., Yamada, T., Chen, C., Kawashima, S., Mellor, J., Linghu, B., Kanehisa, M., Stuart, J.M., and DeLisi, C. 2007b. VisANT 3.0: New modules for pathway visualization, editing, prediction and construction. Nucleic Acids Res. 35:W625‐W632.
  Hu, Z., Hung, J.H., Wang, Y., Chang, Y.C., Huang, C.L., Huyck, M., and DeLisi, C. 2009. VisANT 3.5: Multi‐scale network visualization, analysis and inference based on the gene ontology. Nucleic Acids Res. 37:W115‐W121.
  Hu, Z., Chang, Y.C., Wang, Y., Huang, C.L., Liu, Y., Tian, F., Granger, B., and Delisi, C. 2013. VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies. Nucleic Acids Res. 41:W225‐W231.
  Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., and Tanabe, M. 2012. KEGG for integration and interpretation of large‐scale molecular data sets. Nucleic Acids Res. 40:D109‐D114.
  Kim Kjaerulff, S., Wich, L., Kringelum, J., Jacobsen, U.P., Kouskoumvekaki, I., Audouze, K., Lund, O., Brunak, S., Oprea, T.I., and Taboureau, O. 2013. ChemProt‐2.0: Visual navigation in a disease chemical biology database. Nucleic Acids Res. 41:D464‐D469.
  Lee, T.I., Rinaldi, N.J., Robert, F., Odom, D.T., Bar‐Joseph, Z., Gerber, G.K., Hannett, N.M., Harbison, C.T., Thompson, C.M., Simon, I., Zeitlinger, J., Jennings, E.G., Murray, H.L., Gordon, D.B., Ren, B., Wyrick, J.J., Tagne, J.B., Volkert, T.L., Fraenkel, E., Gifford, D.K., Young, R.A. 2002. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298:799‐804.
  Linghu, B., Snitkin, E.S., Hu, Z., Xia, Y., and Delisi, C. 2009. Genome‐wide prioritization of disease genes and identification of disease‐disease associations from an integrated human functional linkage network. Genome Biol. 10:R91.
  Liu, X., Zhu, F., Ma, X.H., Shi, Z., Yang, S.Y., Wei, Y.Q., and Chen, Y.Z. 2013. Predicting targeted polypharmacology for drug repositioning and multi‐target drug discovery. Curr Med Chem. 20:1645‐1661.
  Mellor, J.C., Yanai, I., Clodfelter, K.H., Mintseris, J., and DeLisi, C. 2002. Predictome: A database of putative functional links between proteins. Nucleic Acids Res. 30:306‐309.
  Mewes, H.W., Frishman, D., Guldener, U., Mannhaupt, G., Mayer, K., Mokrejs, M., Morgenstern, B., Munsterkotter, M., Rudd, S., and Weil, B. 2002. MIPS: A database for genomes and protein sequences. Nucleic Acids Res. 30:31‐34.
  Povey, S., Lovering, R., Bruford, E., Wright, M., Lush, M., and Wain, H. 2001. The HUGO Gene Nomenclature Committee (HGNC). Hum. Genet. 109:678‐680.
  Sanseau, P., Agarwal, P., Barnes, M.R., Pastinen, T., Richards, J.B., Cardon, L.R., and Mooser, V. 2012. Use of genome‐wide association studies for drug repositioning. Nat. Biotechnol. 30:317‐320.
  Shigemizu, D., Hu, Z., Hung, J.H., Huang, C.L., Wang, Y., and DeLisi, C. 2012. Using functional signatures to identify repositioned drugs for breast, myelogenous leukemia and prostate cancer. PLoS Comput. Biol. 8:e1002347.
  Spiro, Z., Kovacs, I.A., and Csermely, P. 2008. Drug‐therapy networks and the prediction of novel drug targets. J. Biol. 7:20.
  Suderman, M. and Hallett, M. 2007. Tools for visually exploring biological networks. Bioinformatics 23:2651‐2659.
  Tian, X.Y. and Liu, L. 2012. Drug discovery enters a new era with multi‐target intervention strategy. Chin. J. Integr. Med. 18:539‐542.
  Tong, A.H., Evangelista, M., Parsons, A.B., Xu, H., Bader, G.D., Page, N., Robinson, M., Raghibizadeh, S., Hogue, C.W., Bussey, H., Andrews, B., Tyers, M., and Boone, C. 2001. Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294:2364‐2368.
  Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi‐Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., and Rothberg, J.M. 2000. A comprehensive analysis of protein‐protein interactions in Saccharomyces cerevisiae. Nature 403:623‐627.
  Yanai, I. and DeLisi, C. 2002. The society of genes: Networks of functional links between genes from comparative genomics. Genome Biol. 3:research0064.
  Yildirim, M.A., Goh, K.I., Cusick, M.E., Barabasi, A.L., and Vidal, M. 2007. Drug‐target network. Nat. Biotechnol. 25:1119‐1126.
Key References
  Hu et al., 2004. See above.
  Introduces the first release of VisANT as an integrative visualization tool for biological networks, with the support of exploratory navigation to walk through interactions based on a few initial genes or proteins of interest.
  Hu et al., 2005. See above.
  Introduces a primary implementation of Metagraph in VisANT to support the integration of context information (such as protein complex, functional modules, etc.) into the network. It also introduces the unique topological analyses (e.g., exhaustive search of shortest paths between two nodes) that are dynamically linked to the network.
  Hu et al., 2007a. See above.
  Introduces details of Metagraph to address the specific features of biological networks.
  Hu et al., 2007b. See above.
  Introduces the Metagraph application in pathway visualization and analysis.
  Hu, Z., Snitkin, E.S., and DeLisi, C. 2008. VisANT: An integrative framework for networks in systems biology. Brief. Bioinform. 9:317‐325.
  Explains the design principals and key development of VisANT system.
  Hu et al., 2009. See above.
  Introduces multi‐scale network visual analysis and inference with integrated Gene Ontology (GO), as well as a sophisticated GO explorer to facilitate the visual navigation and application of GO hierarchy.
  Hu et al., 2013. See above.
  Introduces VisANT's new network‐based cap‐ abilities of translational sciences to convert our understanding of basic biological knowledge into effective ways to treat and prevent diseases, with integrated disease and therapy hierarchies in the Hierarchy Explorer.
Internet Resources
  VisANT homepage.
  The VisANT user's manual.
  Free source of Java run‐time environment 1.4 or above. Refer to VisANT user manual for detailed instruction.
PDF or HTML at Wiley Online Library