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4. For Cytoscape App Developers

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1. Randomnetworks Generates random network or randomizes already loaded network RDFScsape Allows to query visualize and reason on ontologies represented in OWL or RDF within Cytoscape Reactome Fls Accesses to Reactome Functional interaction Fl network to perform pathway analyses such as identification of pathways enriched with proteins in given network ReConn Communicates with reactome server to load pathway data onto Cytoscape Additional features such as integration of expression data are supported RemainingDegreeDistribution Calculates remaining degree excess degree distribution ReOrientPlugin Layouts node positions according to reference Cytoscape session file RubyScriptingEngine Provides Ruby Script API ScriptEngineManager Manages scripting engines for Cytoscape Available as part Supports Ruby JavaScript Groovy and of core Python SFLDLoader Represents structural protein families and their homologs by graph on Cytoscape ShortestPath Finds shortest pathway between two selected nodes SimTrek Assesses similarity of gene ontologies for given genes and their neighbours All files must be installed in plugin folder StringWSClient Retrieves interactions associated with input protein name structureViz Enables user to traverse from biological In Progress networks to detailed view of their structures Superpathways Plugin Downloads and integrates multiple pathways from Wikipathways TransClust Clusters a given similarity g
2. as link to iReflndex is provided Finds clusters where member nodes show Available in App significant changes in expression levels Store Provides Java Script API Available as part of core Detects highly connected sub networks where most genes show similar expression behavior Enables import of KEGG XML file via import menu mcl new MetaNetter MetanodePlugin2 MetScape MiMIplugin MiSink NamedSelection Clusters given network Subnetwork is indicated by set of nodes and they are shown by selecting subnetwork number Clusters a given network based on vertex Available in App weighting by local neighborhood density Store and outward traversal from a locally dense seed protein to isolate the dense regions Infers of metabolic networks based on high resolution metabolomic data Enables user to define meta node a Available as part group of nodes Meta nodes can have of core hierarchy Loads human or mouse metabolic network Sophisticated GUI is provided which allows user to perform various tasks including gene expression analysis along the pathways Retrieves interactions associated with input IDs User can add own annotations to genes which can be viewed by different users Clusters a given network based on agglomerative clustering algorithm very similar to MCODE but it uses a modified vertex weighting strategy and can factor in a measure of network modularity Adjustment of only few paramete
3. April 19 2013 Welcome Summary e Cytoscape v3 0 1 is now available for immediate download e Relative to v3 0 0 it contains over 100 bug fixes e It is ready for use by all segments of the Cytoscape community e It continues v3 0 0 s core feature set specifically It is a major reorganization of Cytoscape 2 x s code and user interface o It contains improvements for all segments of the Cytoscape community o Itis upward compatible and can coexist with previous Cytoscape versions o The most popular plugins from previous versions are available with more to follow o Support offerings have been updated and broadened e What todo next Dear Cytoscape User We are proud and pleased to release Cytoscape v3 0 1 This new release contains many improvements on v3 0 0 released Feb 1 2013 all of which immediately benefit Cytoscape users the most important part of the Cytoscape ecosystem If you are a new or casual Cytoscape user welcome aboard Feel free to either read on or jump to the end of this letter for a quick start For clarity references to Cytoscape 3 x apply to all Cytoscape versions 3 0 0 and later For Cytoscape v2 x Users Previous Cytoscape releases through v2 8 3 focused on adding numerous annotation import layout analysis and visualization features all of which have combined to deliver critical insights into biological processes of interest to Cytoscape s broad and loyal user community In fact man
4. Developers Section 4 General Interest Try getting oriented by reading General Background Section 5 Cytoscape App Store Section 6 Then try browsing New Features Section 7 App Status Section 8 Support Offering Section 9 Future Plans Section 10 To get your feet wet try For New Users Section 1 1 For New Cytoscape Users What is Cytoscape Cytoscape is software that can help you visualize complex networks as graphs representing relationships between genes proteins or other entities Cytoscape tracks and displays these entities as graph nodes and relationships between them as graph edges Cytoscape per se does not assign meaning to either nodes or edges you can assign your own meanings to them and you can add your own node or edge attributes e g name measurements states etc that customize your graph to represent semantics important to you While Cytoscape provides simple analytics and visualizations others are available as apps from the Cytoscape App store see Section 6 What Do I Need Before I Can Use Cytoscape At the very least you must provide Cytoscape with a list of nodes You can also provide a list of edges and attributes You can enter your graph manually or import it from your own files Cytoscape supports a wide variety of file formats including text and Excel Cytoscape can also load pre configured networks e g from BioGRID so you can leverage them without having to enter them your
5. are available from the new Cytoscape App Store which you can browse directly Section 6 Note that some v2 x apps have been incorporated directly into Cytoscape and need not be downloaded or installed Consult the Apps Status table Section 8 to see a list of these apps Note that v2 x plugins are not compatible with v3 x apps and vice versa If you rely on v2 x plugins that are not yet available for v3 x you may need to remain with v2 x instead of upgrading to v3 x Note also that the Cytoscape community is converting v2 x plugins to v3 x apps you might occasionally revisit the App Store to see if an app you need becomes available What s New in v3 x As described in the Welcome letter above v3 x incorporates a number of new features Section 7 and productivity enhancing support offerings Section 9 including the Cytoscape App Store Section 6 The General Background section Section 5 describes the rationale advantages and issues with v3 x Will Support for v2 x Continue Cytoscape v2 x will be supported by the Cytoscape community for now but with fewer upgrades and support options over time Can I use v2 x and v3 x at the Same Time You can experiment with v3 x by installing it on your workstation you can use both v2 x and v3 x on the same workstation How to Prepare for v3 x 1 If you have already installed a v3 0 0 beta version please uninstall it before proceeding The Cytoscape v3 0 0 release version can coexist
6. d putative function for those genes Genoscape GoogleChartFunctions GPML Plugin GraphletCounter GraphMLReader Creates image from attribute values URL using the Google Chart API Enables import of GPML file via import menu Calculates graphlet small connected non isomorphic subgraph degree distribution Loads interactions or pathways in GraphML Available as part format of core GroovyEngine Provides scripting interface of Groovy GroovyScriptingEngine GroupTool HiderSlider HyperEdgeEditor IgraphPlugin IntActWSClient Interference iRefScape jActiveModules JavaScriptEngine KeyPathwayMiner KGMLReader Provides scripting interface of Groovy Enables user to defines groups of nodes For In Progress each group basic information such as number of nodes will be displayed on the panel Provides user sliders which can hide nodes whose continuous attribute is below threshold specied by sliders Enables one to create hyper edge by Cytoscape editor Brings some functionality of Igraph such as layouts into Cytoscape Mac only Retrieves interactions associated with Replaced by input IDs PSICQUIC Evaluates the topological effects of single or In Progress multiple nodes removal from a network using the effect to Radiality Closeness Betweenness Centroid Value and Eccentricity Retrieves interactions associated with input IDs Detailed information for each interaction as well
7. d genes Visualizes domain domain interactions which connect pairs of interacting proteins Retrieves interactions associated with input IDs Detailed information associated with interactiong proteins can also be obtained Dynamically change colors of nodes like a movie according to their expression level across many conditions Calculate edge length in the main network view window and stores them as edge attributes length Records selected edges and provides some functionality for them ex hiding recorded edges Performs keyword search Wildcards Available as part logical operators etc are allowed of core Visualizes enrichment of specific functions GO terms by interactions between functions Searches for differentially altered links ina given network using multiple set of expression data Makes a similarity network where nodes are genes and edges denote highly correlated genes Performs stochastic simulation of chemical reaction networks Visualizes fluxes as visual effect to edges on Cytoscape network Performs one of the fastest multilevel force directed Layouts called FM3 Layout introduced by Hachul S et al 2005 FunNetViz GeneMANIA Integrates and visualizes co expression network with biological role of transcripts e g GO terms Centrality measures are equipped Generates interaction networks from Available in App public databases based on user s list of Store genes Also provides annotation an
8. ded successor to v2 x with development and support of v2 x expected to diminish and disappear over time in favor of v3 x We believe that users will benefit most directly from the v3 x by e experiencing fewer core and app bugs from one release to the next e the availability of more and richer apps due to developers spending less time tracking and fixing bugs e more core features with higher biological and logistical value due to improved flexibility provided by interface driven development During the creation of v3 x a number of features were added as listed in the New Feature Table below As a result we incurred a number of current and future costs Cost Reason Time frame for addressing Slower startup time OSGi module inventorying near to medium term Loss of plugins Lag in upgrading less popular as needed plugins 1 A www osgi org also used as the basic framework for Eclipse and numerous commercial products 6 The Cytoscape App Store The Cytoscape App Store is new in v3 x and targets broad demographics through specific features Cytoscape User Benefit New or Casual Find Cytoscape functionality easier via familiar paradigms of search and tag navigation Power or Frequent Find and install apps easier and provide crowdsourced rating and reviews Plugin Developers Have a dedicated presence for their work including a direct line to their users and critical statistics to justify their development on the Cytoscap
9. e platform Furthermore the App Store supports contests and social incentives that encourage critical technical and community development including porting analytics rating reviewing and so on Note that the App Store supports only Cytoscape v3 x and does not contain plugins compatible with earlier Cytoscape versions Likewise plugins that work with earlier versions are not compatible with v3 x Section 8 contains a list of apps available for v3 x To access the App Store access Cytoscape s new Apps menu and choose the App Manager menu item or use your browser to surf directly http apps cytoscape org 7 New Feature Table Feature Beneficiary Manual Section Welcome screen New users for solicitousness casual 3 1 3 Launch the and power users for convenience Application Import network Casual and power users for ease of 7 Creating Networks use Edge bend visual property Paper and presentation writers 12 4 Visual Attributes Graph Attributes and Visual Mappers Edge bundling Users of high degree networks 11 3 Edge Bundling Network annotations Paper and presentation writers Grouping Users of hierarchical networks Enhanced search Users of highly populated networks 13 1 Enhanced Search Multiple network All users 4 2 Network management Management 8 App Status Table For the most up to date list of apps see the App Store described in Section 6 A URL for our development list is shown below as a list o
10. f apps and their status at the time this letter was authored https docs google com spreadsheet ccc key OArzUWDuvdBn dDIOROkKwWOERjN1ZhcDZseCOOdVZNNIE amp authkey CMGe99EM gid 0 App Capability Status addParentNeighbors For a selected node in child network adds neighboring nodes from a parent network AdvancednetworkMerge Merges multiple networks AgilentLiteratureSearch Mines scientific literatures to find ones Available in App related to search term and to create Store interaction network based on the search result AllegroMCODE Very fast clustering based on MCODE algorithm APCluster Uses affinity propagation described in Frey BJ and Duec D 2007 to perform clustering APID2NET Downloads PPI data from http bioinfow dep usal es apid and performs various analyses including protein motif GO hub identification etc through the original GUI Equipped with impressing rainbow coloring of nodes BiLayout Finds a bipartite network for two sets of user selected nodes and performs layout Calculates overrepresented GO terms in Available in App the network and display them as anetwork Store of significant GO terms bioCycPlugin Loads any pathway in bioCyc database In Progress Original panel provides useful information for each node BiomartClient Retrieves attributes associated with given gene or protein BioNetBuilder Through the wizard user can easily construct networks from public databases User can also create intero
11. frame New Casual users TBD Additional Visualizations TBD BD Additional Analytics Wallpaper Collection Searchable Web Site Case Studies Cytoscape Clinics New Casual User Power User App Developer Publicize good results associated with Cytoscape Fast access to manuals tutorials group transcripts clinic transcripts Streamlined productivity Chat rooms give instant response based on community availability T All users potential users general public All users New Casual Users All users
12. logs BioQualiPlugin Performs consistency check of regulatory network and expression data Bisogenet Retrieves interactions associated with input IDs Sophisticated UI gives links to GO KEGG etc BLAST2similarityGraph Visualizes BLAST similarity as graph Integrates interaction datasets from different resources to explore the integrated network and to perform confidence analysis for interactions User can give weight to each interaction set which will be used for the level of confidence CalculatenodeDegree Simply calcuates degree for selected single node CentiScaPe Calculates topological characteristic values Available in App ex Centralities for each node Store ChemViz Visualizes chemical structure of each compound in chemical network with original interface ClueGO Creates and visualizes a functionally Available in App organized GO term network or pathway Store from given interaction network clusterMaker Clusters densely connected nodes and node In Progress attributes i e expression data in a given network Results of these two types of clustering can be analysed in the integrated interface ClusterONE Finds overlapping protein complexes ina Available in App protein interaction network Clusters are Store visualized by original interface with their p values ClusterViz Clustering based on FAG EC EAGLE or MCODE Found cluster can be subjected to GO enrichment analysis commandTool Provides simple command line i
13. nterface to Cytoscape Comm Finder Clustering based on QCUT HQCUT MCL MCODE Commonattributes Find attributes shared between selected nodes ConsensusPathDBplugin Retrieves interaction evidences for given pair of genes or proteins CyAnimator Creates animation based on added frames of network views CyClus3D Clusters a given network based on three node motifs Accepts multiple types of interactions Cluster ID is given to edge attributes EdgeCluster CyGoose Provides Gaggle Boss which routes data from one application to another CyThesaurus ID Mapping Performs ID mapping using BridgeDb and other public or custom database sources cytoHubba Predicts and explores important nodes and subnetworks in a given network by several topological algorithms Cytoprophet CytoSaddleSum CytoscapeRPC CytoSEED CytoSQL DisGeNET DomainGraph dynamicXpr edgeLengthPlugin edgeLister EnhancedSearch EnrichmentMap ExprEssence ExpressionCorrelation FERN FluxViz Finds enriched function based on sum of weight scores Allows user to query and modify networks through an XML RPC connection Enables users to view manipulate and analyze metabolic models created by the Model SEED The reactions are organized into a set of maps based on each reaction s membership in KEGG pathways Retrieves attributes from SQL databases by invoking query command Queries and analyzes networks of diseases and their associate
14. raph VennDiagramgenerator Generates a Venn Euler Diagram of shared In Progress nodes for selected networks VennDiagrams Calculates overlap between multiple groups In Progress of interactions and creates Venn diagram VistaClaraPlugin Provides effective visualization and analysis platform to analyse expression data ona given network WordCloud Summarizes functions of interacting clusters as logos where sizes of logo represents frequencies of these functions 9 Support Offering Table Feature Cytoscape Google Groups Helpdesk Discuss User Manual Installation Guide Tutorials Presentation Slides on Web Site Code Snippets 3 new feature Purpose Community response on best effort basis Comprehensive manual Cytoscape installation Streamlined productivity Enable casual learning Commonly used App development code Beneficiary All users All users New Casual users All users All users App Developers mailto cytoscape helpdesk googlegroups com mailto cytoscape discuss googlegroups com http wiki cytoscape or UserManual Section 3 of http wiki cytoscape org Cytoscape 3 UserManual http opentutorials cgl ucsf edu inde x php Portal Cytoscape3 https speakerdeck com cytoscape Cytoscape 3 http wiki cytoscape org Cytoscape_3 AppDeveloper Cytoscape_3 App Co okbook 10 Future Plans Table Feature Movies Purpose Clear and interactive engagement Beneficiary Time
15. rder get the benefits of improved stability the Cytoscape team found it necessary to change the relationship between plugins apps and the Cytoscape core Many plugins have been ported to v3 x see Section 8 The porting exercise is substantial and once a plugin is converted to an app it will continue to work at least until v4 0 is released there is no v4 0 planned at this time For more on this topic see http wiki cytoscape org Cytoscape_3 CoreDevelopment Motivation Should I Convert My v2 x Plugin to a v3 x App Yes Cytoscape v2 x will be supported by the Cytoscape community for now but with fewer upgrades and support options over time How Do I Get Started With App Development To get started with app development http wiki cytoscape org Cytoscape_3 AppDeveloper To convert a v2 0 plugin to a v3 x app refer to http wiki cytoscape org Cytoscape_3 AppDeveloper PluginPortingGuide For a broader view of the Cytoscape system including the Core refer to http wiki cytoscape org Cytoscape_3 CoreDevelopment Are there App Samples Yes See Also note the App Cookbook http wiki cytoscape org Cytoscape 3 AppDeveloper Cytoscape 3 App Cookbook 5 General Background The overall mission of Cytoscape is to be a freely available worldwide asset supporting network analysis and visualization for systems biology science The major focus of v3 x is the modularization and rationalization of code to solve stability issues in
16. rs are necessary Provides network interface to MiSink enabled Web sites including DIP Predicts gene regulatory network from biological annotations and expression data Systematically partition the given graph and layout and color nodes based on GO terms Assign name to selected nodes and after unselection enables user to re select the nodes according to the name NCBIClient Imports various data from NCBI database NCBlEntrezgeneUserinterface NeighborHighlight NetAtlas Imports various data from NCBI database Available as part of core Highlights the current node and all its neighboring nodes and edges when the user hovers the mouse over it Identifies densely connected and biopartite network modules based on combination of a unique neighbour sharing score with hierarchical agglomerative clustering Integrates gene expression data of multiple tissues ex from Symatlas into pre loaded network genes showing characteristic expression in specified tissues can be filtered and colored NetCirChro Visualizes interaction network on circular genome Original GUI with some network analysis functions shortest path degree distribution etc are equipped NetMatch Finds user defined network motifs in a given network network motif can be created and edited using original GUI NetworkAnalyzer Computes basic properties of whole Available as part network degree distribution clustering of core coefficien
17. self Can Cytoscape Help Me Get Started Yes The Cytoscape team had provided many resources tailored for all kinds of users see Section 9 To start there is an Installation Guide and numerous tutorials Once you load your graph you may find additional useful analytics and visualizations at the App Store see Section 6 Which Cytoscape Version Should I Use Generally you should use v3 0 1 the newest version v2 x has been in the field for several years and will be supported into the future but over time v3 x and successors will be better supported Note that if you have already installed v3 0 0 you can install v3 0 1 without uninstalling v3 0 0 How to Download and Install v3 x e Surf to http www cytoscape org click on the Download Cytoscape button and follow the prompts e Be sure to consult with the Release Notes viewable via the Release Notes button for issues and solutions pertaining to your installation e Surf to http www cytoscape org click on the User Manual button and follow the instructions in the Launching Cytoscape section 2 For Casual Cytoscape Users If you re confident of your Cytoscape skills please read the Power Users information Section 3 If you re Cytoscape skills are rusty please continue with the New Users information Section 1 3 For Cytoscape Power Users Is v3 x for Me The answer is most likely yes provided you use the apps formerly known as plugins available for v3 x apps
18. ts centrality etc NetworkEvolution Allows interactive comparative analysis of networks across different species OmicsAnalyzer Integrates omics data such as expression data proteome data etc onto the network to visualize such data by graph on the network OrthoNets Enables simultaneous comparison of interaction network of two species protein domain information can be visualized PanGIA Performs integrated analysis and Available in App visualization of PPIs and genetic Store interactions to infer functional modules and interactions that connect these modules Pathintegrator Integrates pathways in which given proteins are associated PerturbationAnalyzer Evaluates how perturbation of selected nodes affect other nodes in a given network based on level of each node ex protein abundances and law of mass action PhosphositePlus Web Service Integrates phosphorylation related Client Module information into the network PhyloTree Reads a file in phylogenetic tree format Phylip or phyloXML and visualizes it as a network Finds candidate genes in a network that Available in App are associated with user defined target GO Store terms PinnacleZ Searches for subnetworks which can discriminate givein conditions according to PPI network and gene expression data obtained in given conditions PSICQUICUniversalClient Retrieves interactions associated with Available as part input IDs from databases having PSICQUIC of core implementation
19. v2 x encountered as multiple developers pursued multiple agendas Under v2 x internal programmatic interfaces evolved from one release to the next leading to the failure of working plugins over time and negative interactions between otherwise working plugins Ultimately this resulted in loss of programmer and user productivity and undermined community confidence in Cytoscape v3 x addresses these issues by adopting modular coding practices promoted by the OSGi architectural framework This enables both the Cytoscape core and externally developed apps formerly called plugins to evolve independently without compromising unrelated functionality At the logical level Cytoscape leverages OSGi precepts to produce v3 x APIs having cleaner and clearer demarcations between functional areas At the deployment level OSGi enables on the fly substitution of one processing element for another e g apps in order to tailor Cytoscape to meet user requirements at runtime without reinstalling or reconfiguring Cytoscape Creating v3 x occupied an international team of engineers for over a year and represents a strong investment toward reducing future development and support costs and increasing reliability and evolvability With the completion of v3 x we expect to leverage v3 x as a platform to satisfy the evolving needs of multiple stakeholder groups and as a platform enabling research on leading edge analysis and visualization techniques v3 x is the inten
20. version 3 x sooner and with features that support cutting edge investigation A table of apps and their status is presented in Section 8 Finally we recognize that with all new software including version 3 x there are growing pains While we hope our users will learn to love v3 x s new features users may also expect to relearn rationalized features and occasionally uncover a bug With version 3 x we are rolling out new manuals tutorials web pages and support channels that we hope can create and maintain highly productive experiences for all types of Cytoscape users A table describing Cytoscape support is presented in Section 9 We are very excited to make this release and hope you find it an indispensable tool in your research To get you started we have provided additional introductory material to get you started on the right foot and we have also provided background material for general interest Please let us know how we re doing and how we can better advance your research The Cytoscape Team What to Do Next We hope to help you use Cytoscape in the most productive way Your next steps depend on how experienced you are with Cytoscape and what you would like to do In the table below please find the category that best describes you and proceed accordingly Type of Cytoscape User Where to Read Next New For New Users Section 1 Casual For Casual Users Section 2 Power For Power Users Section 3 App Developers For App
21. with v3 0 1 and does not need to be uninstalled 2 Consult the Apps Status table Section 8 to verify that the apps you need are available Some apps have become part of the Cytoscape core and you won t need to download them Other apps are available in the Cytoscape App store described in Section 6 3 Browse the New Features table Section 7 to see what we have added since v2 x Browse the Future Plans table Section 10 and Support Offering table Section 9 to see where the Cytoscape community is going How to Download and Install v3 x e Surf to http www cytoscape org click on the Download Cytoscape button and follow the prompts e Be sure to consult with the Release Notes viewable via the Release Notes button for issues and solutions pertaining to your installation e Surf to http www cytoscape org click on the User Manual button and follow the instructions in the Launching Cytoscape section 4 For Cytoscape App Developers Cytoscape manages graph storage and display and contains a number of common analytic and visualization functions App Developers may write apps formerly known as plugins to perform problem specific analytics graph layouts or other visualizations Before starting app development you should be familiar with overall Cytoscape usage and functionality see the Power Users section Section 3 to start working with v3 x if you have not already done so Note that v2 x plugins do not work with v3 x In o
22. y of these features were created and contributed by Cytoscape users themselves using Cytoscape s plugin architecture Version 3 x marks a major reorganization of Cytoscape program code it enables us to deliver additional features more quickly and reliably than before including improvements that benefit new users casual users power users and app developers Along the way some features were changed to allow them to better interoperate with other features some little used features were dropped and user interface was improved We are particularly excited about the new Cytoscape App Store described below which affords users access to the growing collection of apps formerly called plugins produced by fellow Cytoscape users A table of new features is presented in Section 7 While version 3 x is upwardly compatible with previous Cytoscape versions i e it can load analyze and display networks and attributes stored using previous versions it can coexist with previous versions on the same workstation It is not necessary to uninstall previous versions before installing version 3 x and you can choose to use both on the same workstation Version 3 x is still a work in progress and continues to evolve due to the outstanding efforts of its vibrant worldwide development community Notably while the Cytoscape team has ported the most popular plugins as apps from previous versions porting less popular plugins was deferred so as to deliver

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