miRScape: A Cytoscape Plug-in to Annotate Biological Networks ...

miRScape: A Cytoscape Plug-in toAnnotate Biological Networks withmicroRNAsAlfredo Ferro, Rosalba Fare clic Giugno, per Alessandro modificare Laganà, lo stile Misael del Mongiovì, sottotitolo Giuseppe dello PigolA, schema Alfredo PulvirentIDipartimento di Matematica e Informatica, UniversitA’ di Catania,Viale A. Doria 6, I-95125 Catania, Italy{ferro, giugno, lagana, mongiovi, pigola, apulvirenti}@dmi.unict.itGary BaderBanting and Best Department of Medical Research and Department of Medical Genetics and Microbiology,University of Toronto, 160 College St, Toronto, Ontario, CanadA M5S 3E1gary.bader@utoronto.caDennis ShashaCourant Institute of Mathematical, Sciences, New York University,251 Mercer Street New York, NY 10012, USAshasha@cs.nyu.edu27/07/09

Introduction and MotivationsIn the last few years there has been an increasing interest inmining biological networks involving miRNAs;Recent works proved the existence of functional interactionsamong miRNAs;miRScape is the first Cytoscape plugin (www.cytoscape.org)to mine biological networks annotated with microRNAs;It makes use of miRo’, a knowledge base (available at thefollowing web site http://ferrolab.dmi.unict.it), whichintroduces a new layer of associations among genes (functions,processes, diseases related) based on miRNAs annotations;27/07/09

Introduction and MotivationsmicroRNAs (miRNA) are single stranded RNA molecules of21-23 nucleotides which regulate gene expression;They are involved in several processes, functions and diseases;The knockout of a single miRNA may dramatically affect thephenotype of an organism [Couzin J. Erasing microRNAs reveals their powerful punch. Science2007;316(5824):530];A miRNA may target more than one gene, often in several sites, and one gene may be targeted by many miRNAs actingcooperatively [Ambros V. The functions of animal microRNAs. Nature 2004;431:350-355];Mining on gene networks annotated with miRNAs is needed;Moreover, analyzing network of interactions between genes and miRNAs may be useful;27/07/09

mirScape plug-inmiRò web pagesAnnotateInteraction netwoksmiRScapeRetrieve data about genes,miRNAs,Diseases, Functions, ProcessesCytoscape27/07/09

Mirò: the miR-Ontology databasewww.ferrolab.dmi.unict.it●Using miRScape the user is able to identify andhighlight relations involving genes present in thenetwork with specific functions, process and diseasesthrough the selected miRNAs;●The miRò knowledge base stores miRNAs annotatedwith additional information coming from miRBase;●It also includes experimentally supported miRNAtargets coming from miRecords and predicted targetstaken from the TargetScan , PicTar, and miRanda;●The target ontologies (processes and functions) are obtained from the Gene Ontology Database (GO);●The gene-disease relations come from the Genetic Association Database (GAD), which is a database ofhuman genetic association studies of complex diseases and disorders;●All the data are collected and maintained up-to-date in a MySQL database accessible through a webinterface;27/07/09

Cytoscapewww.cytoscape.orgCytoscape is anopen sourcebioinformaticssoftware platformfor visualizingand analyzingbiologicalinteractionnetworks;It is multiplatform(Java);27/07/09

Cytoscape: Featureswww.cytoscape.orgCytoscape supports a lot ofstandard network and annotationfile formats including: SIF (SimpleInteraction Format), GML,XGMML, BioPAX, PSI-MI, SBML,OBO, and Gene Association;Filter the network to selectsubsets of nodes and/orinteractions;Search nodes and edges;Customize network data displayusing powerful Visual Styles;27/07/09

Cytoscape: Pluginswww.cytoscape.orgAdditional features are available as plugins:In Cytoscape you can write your own pluginfor data analysis/import/visualization bywriting Java code;Several plug-ins are available for networkand molecular profiling analyses, newlayouts, additional file format support,scripting, graph matching and connectionwith databases;Plug-ins can easily installed by just one clickfrom Plugin Manager;27/07/09

Cytoscape: Pluginswww.cytoscape.orgTopology analysis:Network Analyzer,ShortestPaths CentiscaPe;Find clusters (highlyinterconnected regions):MCODE;Motif Finder:Motif Finder Plugin;Metabolica Plugin;Graph Matching:NetMatch;27/07/09

miRScape: Search by Genehttp://ferrolab.dmi.unict.itThere are two different ways to querymiRò database: by gene or by miRNA;Selecting a set of genes in a network itis possible to retrieve all miRNAs,Functions, Processes and Diseasescorrelated with selected genes;The gene searching in miRò is done byNCBI id, Official name and aliases;All results are linked to the miRò website;27/07/09

miRScape: Annotating Networkshttp://ferrolab.dmi.unict.itMoreover, it is possible to annotate the network withinformation about related miRNAs, Functions, Diseases, andProcesses;Eventually the network can be saved with these additionalinformation.27/07/09

miRScape: Search by miRNAhttp://ferrolab.dmi.unict.itIt is possible to retrieve information aboutall genes correlated to selected miRNAs;The process can be done searching only formiRNAs:1. Validated (Experimentally by miRecords);1. TargetScan (Lewis BP et al. Conserved seed pairing, often flanked by adenosines,indicates that thousands of human genes are microRNA targets. Cell 2005;120:15-20);1. Pictar (Krek A et al. Combinatorial microRNA target predictions. Nat Genetics2005;37:495-500);1. MiRanda;It is also possible getting information about: Functions,Processes,and Diseases related to miRNAs;Genes in the network correlated with selected miRNAs will behighlighted;27/07/09

Example: Search by Gene and annotateNetworkshttp://ferrolab.dmi.unict.it27/07/09

Example: Create a network genes-miRNAshttp://ferrolab.dmi.unict.it27/07/09

Example: Highlight Specific Interactionshttp://ferrolab.dmi.unict.it27/07/09

Example: Search by miRNAhttp://ferrolab.dmi.unict.it27/07/09

Conclusions miRScape represents the first tool able to annotatenetworks with miRNAs related information coming fromseveral distributed databases. This was achieved by makinguse of miRò which can be viewed as a unified access pointto these remote databases. One of the crucial functions available on mirScape is thepossibility to highlight hidden relations among clustersof genes at miRNA level. This capability represent the basicstep for any analysis requiring mining.27/07/09

miRScape: Future Workhttp://ferrolab.dmi.unict.it●Using different kinds of attribute in order to query miRò database;●Adding datamining facilities: Association rules etc…;●New visualization layouts for very large networks;27/07/09

Download miRScapehttp://ferrolab.dmi.unict.it●Download Cytoscape: www.cytoscape.org●miRò web site: http://ferrolab.dmi.unict.it●Plugin download and bugs report: contact ferro@dmi.unict.itThank You……27/07/09