Home

Cytoscape Manual

1. Desktop Il x File Edit Data Select Layout visualization Plugins CytoPanels Help hsXOx 8 EC fib EA gt gt x CytoPanel 1 galFiltered sif gt child gt child gt child fg Network 362 0 242 0 99 0 B alFitei36 1 6169 0 27 0 80 25 66 0 4 gt Nodes 36 1 selected Edges 51 0 selected Welcome to Cytoscape 2 2 The network manager top right tree view in CytoPanel 1 shows the networks that are loaded Clicking on a network here will make that view active in the main window if the view exists green highlighted networks only Each network has a name and size number of nodes and edges which are shown in the network manager If a network is loaded from a file the network name is the name of the file Some networks are very large thousands of nodes and edges and can take a long time to display For this reason a network in Cytoscape may not contain a view Networks that have a view are highlighted in green and networks that don t have a view are highlighted in red You can create or destroy a view for a network by right clicking the network name in the network manager or by choosing the appropriate option in the edit menu You can also destroy previously loaded networks this way In the picture above seven networks are loaded six green ones with views and one red ones without a view
2. NSS Aa sm sm term print gt gt sys stderr goodElements d goodElements print gt gt sys stderr badElements d badElements Script 1 parseAssignmentsToFlatFileFromGoaProject py tools bin python import sys def fixCanonicalName rawName for instance trim YBRO85W ANC3 to YBROS85W bar rawName find if bar 0 return rawName return rawName bar def fixGoID rawID bar rawID find 1 return rawID bar SE Ar ENE NENE E TT AEST AP OEE EO s RE CEN def readGoaXrefFile filename lines open filename read split result for line in lines if len line lt 10 continue tokens line split t ipi tokens 2 np tokens 5 semicolon np find if semicolon gt 0 np np semicolon if len gt 0 and len np gt 0 result ipi np return result P a a Ee enn ae Gan Lae eS TC Dmm mE if len sys argv 3 print error parse lt gene_associations file from GO gt lt goa xrefs file gt sys exit associationFilename sys argv 1 xrefsFilename sys argv 2 species Homo sapiens ipiToNPHash readGoaXrefFile xrefsFilename 63 tester IPI00099416 print hash size d
3. interactions with blue edges and Protein Protein interactions with et Edgzunetype Edge Sauce ron Default 4 Mapping gt 4 Load a sample network From the main menu select File InteractionTypeColr 7 gt Load gt Graph and select sampleData galFiltered sif _Duplcate Rename Delete e Select Visualization gt Set Visual Properties Map Attribute Interaction v J e Select New to create anew Visual Style Name your style Sample3 Seed Mapping with Random Colors J e Click the Define button to define the newly created Visual Style e In the Set Visual Properties Dialog box select Edge Attributes gt Edge Color e Click the New button in the mapping panel e You will be prompted to select a mapping type passthrough mapper discrete mapper or continuous mapper for an overview of the differences between these mappers please refer back to section 8 2 Select discrete Apply to Network Hi Close J mapper and enter a descriptive name For Cytoscape Desktop example enter InteractionTypeColor Edit Date Selec Layou Visualizatic Plugin CytoPane Help Filter e Z LA x From the Map Attribute pull down menu select 9 amp Qo interaction You should now see two buttons eoe galFiltered sif one for pd Protein DNA interac
4. section of the dialog These properties are Plugin Location 5 D 5 plugins HierarchicalLayout jar configurable via Add Modify and Delete depression us operations plugins filter jar plugins yLayouts jar plugins yeast context jar The specification of plugins to be loaded into TOT m oca Cytoscape at startup time is also supported in cytoscape props and accessible in this dialog under Note Changes to these properties and plugins will be saved on E B 4 B application exit and available on next start To use these new the Plugins section In this special case the plugins settings now please exit and restart Cytoscape property specifies a comma separated list of jar E files or URLs to Jar files containing plugins This property is parsed and presented and managed in the Plugins table as at left Add Some common properties are described below Property name Default Valid values Related value command line argument defaultSpeciesName PleaseSpecify species names S this value must match the name in the species first line of the file specified in the bioDataServer s manifest for synonyms e g for yeast synonyms specify Saccharomyces cerevisiae bioDataServer PleaseSpecify annotation manifest and other manifest b file locations BDS viewThreshold 500 integer gt 0 yt VT secondary ViewThreshold 2000 integer gt 0 view Type tabbed tabbed plugins comma separated list
5. within distance 1 that pass the filter Node canonicalName YD Boolean Filter Manage Filters Boolean Meta Filter Create new filter Remove selected filter Filter Name BooleanMeta Available Filters Select objects that pass pr of the selected filters Node gal4RGsig lt 0 0010 Node gal4RGsig lt 0 0010 Uu EE Edge null 0 0 Edge null2 0 0 Node canonicalName YDL Node canonicalName YDL NodeTopology NodeTopology BooleanMeta BooleanMeta nal4RGcin n Y Node gal4RGsig 0 0 Apply selected filter C Negate The Boolean Meta Filter allows you to define a new filter that is a logical combination of existing filters Available filters are displayed By selecting one or more filters you can then choose whether Nodes or Edges pass ALL AND AT LEAST ONE OR or ONLY ONE XOR of the selected filters Once created Boolean filters can then themselves be combined using the Boolean filter to create arbitrarily complex logical combinations of filters Note that unlike the String and Numerical Filters Boolean Filters will need to be assigned a name manually Once created filters are saved for future sessions as long as you exit Cytoscape normally via the exit command in the File menu i e not via ctrl c on Linux 53 Running filters Any available filter can be run by pressing the Apply selected filter button When a filter is applied and m
6. Help Filte CytoPanel 1 Ctrl 1 v CytoPanel 2 Ctrl 2 CytoPanel 3 Ctrl 3 In order for these keyboard short cuts to work the Cytoscape Desktop Window needs to have the focus To give the window focus simply click on it Help 11 The Help menu allows you to launch the online help viewer and browse the table of contents Contents or view the help text associated with a Contents F1 context sensitive selection Context Sensitive By selecting Context Sensitive menu item and then selecting a GUI component the help About related to the selected item is launched The About menu item displays information about the running version of Cytoscape Filters This menu allows you to bring up a user interface for defining and running filters see 10 Filters Filters enable you to extract subnetworks based upon the values Use Filters F7 of node and edge attributes Additional menus may appear depending on the set of Plugins you have chosen to load Network Management Cytoscape 2 2 allows multiple networks to be loaded at a time either with or without a view A network stores all the nodes and edges that are loaded by the user and a view displays them You can have many views of the same network Networks and their optionally associated views can be organized hierarchically An example where a number of networks have been loaded and arranged hierarchically is shown below 12
7. Certain operations in Cytoscape will create new networks If a new network is created from an old network for example by selecting a set of nodes in one network and copying these nodes to a new network via the Select gt To New Network option it will be shown as a child of the network that it was derived from In this way the relationships between networks that are loaded in Cytoscape can be seen at a glance Networks in the top part of the tree in the figure above were generated in this manner 13 The available network views are also arranged as multiple overlapping windows in the network view window You can maximize minimize and destroy network views by using the normal window controls for your operating system The Network Overview Window The network overview window shows an overview or bird s eye view of the network It can be used to navigate around a large network view This feature can be turned on or off via the Visualization menu The red outlined blue rectangle in the overview window shown below can be dragged with the mouse to navigate to a part of the network The size of the navigation rectangle depends on the size of the active view and the zoom level of the view The rectangle is smaller if the view is zoomed in and larger if zoomed out e oko 4 Command Line Arguments and Properties Cytoscape recognizes a number of optional command line arguments including run time specification of network
8. Inc 59 Temple Place Suite 330 Boston MA 02111 1307 USA Everyone is permitted to copy and distribute verbatim copies of this license document but changing it is not allowed This is the first released version of the Lesser GPL It also counts as the successor of the GNU Library Public License version 2 hence the version number 2 1 Preamble The licenses for most software are designed to take away your freedom to share and change it By contrast the GNU General Public Licenses are intended to guarantee your freedom to share and change free softwar to make sure the software is free for all its users This license the Lesser General Public License applies to some specially designated software packages typically libraries of the Free Software Foundation and other authors who decide to use it You can use it too but we suggest you first think carefully about whether this license or the ordinary General Public License is the better strategy to use in any particular case based on the explanations below When we speak of free software we are referring to freedom of use not price Our General Public Licenses are designed to make sure that you have the freedom to distribute copies of free software and charge for this service if you wish that you receive source code or can get it if you want it that you can change the software and use pieces of it in new free programs and that you are informed that you can
9. NumSigGenes intl int2 This line specified the number of genes that were significantly differentially expressed in each condition The first text token must be spelled exactly as shown the rest of the line should contain one integer value for each experimental condition 7 Node and Edge Attributes Cytoscape allows the user to add arbitrary node and edge information to Cytoscape as node and edge attributes Attributes could be for example annotation data on a gene or confidence values in a protein protein interaction These attributes can then be visualized in a user defined way by setting up a mapping from data attributes to visual attributes colors shapes etc See the section on visual styles for a discussion of this Node and edge attribute files are simply formatted A node attribute file begins with the name of the attribute on the first line and on each following line has the name of the node followed by 23 an equals sign followed by the value of that attribute Numbers and text strings are the most common attribute types All values for a given attribute must have the same type For example FunctionalCategory YALOO1C metabolism YAROO2W apoptosis YBLOO7C ribosome An edge attribute file has much the same structure except that the name of the edge is the source node name followed by the interaction type in parentheses followed by the target node name Directionality counts so switching the source and target wil
10. argument to specify the annotation manifest file to read e g b manifest Please note that the s switch which sets the default species for your data is required to exactly match the species named in any annotation file you wish to use Getting and Reformatting GO Data The Gene Ontology GO project is a valuable source of annotation for the genes of many organisms In this section we will explain how to 1 Obtain the GO ontology file 59 2 Reformat it into the simpler flat file Cytoscape uses 3 Obtain an annotation file we illustrate with yeast and human annotation 4 Reformat the annotation files into the simple Cytoscape format Obtain the GO ontology file Go to GO XML FTP ftp ftp zeneontology org pub go xml page Download the latest go YYYYMM termdb xml gz file Reformat GO XML ontology file into a flat file gunzip go YYYYMM termdb xml gz python parseGoTermsToFlatFile py go YYYYMM termdb xml goOntology txt See below for Python script listing Obtain the association file for your organism GO maintains a list of association files for many organisms these files associate genes with GO terms The next step is to get the file for the organism s you are interested in and parse it into the form Cytoscape needs A list of files may be seen at http www geneontology org GO current annotations shtml The rightmost column contains links to tab delimited files of gene associations by species Choose the species y
11. for budding yeast from the flat text file maintained by SGD for the Gene Ontology project and available both at their web site and at GO s shows three yeast ORFs annotated for biological process with respect to GO described further above 2 Following the mandatory title line there are one or more annotation lines each with the form canonicalName ontologyTermID 3 Once loaded this annotation along with the accompanying ontology can be assigned to nodes in a Cytoscape network For this to work the species type of the node must exactly match the species named on the first line of the annotation file The canonicalName of your node must exactly match the canonicalName present in the annotation file If you don t see the expected results when using this feature of Cytoscape check this again as getting either of these wrong is a common mistake Load Data into Cytoscape The easiest way to make annotations available to Cytoscape is by loading annotations into the Cytoscape annotation server This is the default behavior for the official release of Cytoscape The Annotation Manifest You must first create a text file to specify the files you want Cytoscape to load Here is an example from a file which for convenience we usually call manifest ontology goOntology txt annotation yeastBiologicalProcess txt annotation yeastMolecularFunction txt annotation yeastCellularComponent txt Use the Cytoscape b command line
12. for use with the software An up to date Gene_ontology obo file is maintained by the GO project updated every 30 minutes Please download the latest version of this file from 45 http www geneontology org if you intend to use it during analysis In addition to the gene ontology file we also provide gene association files for Yeast and Human gene_association sgd and gene_association goa_human both in the annotations directory Other gene association files can be found at the gene ontology web site Sample Files gene_ontology obo format version 1 0 date 11 08 2005 16 57 saved by midori auto generated by DAG Edit 1 419 rev 3 default namespace gene ontology remark cvs version Revision 1 1 subsetdef goslim yeast Yeast GO slim subsetdef goslim goa GOA and proteome slim subsetdef goslim plant Plant GO slim subsetdef goslim generic Generic GO slim subsetdef gosubset prok Prokaryotic GO subset Term id GO 0000001 name mitochondrion inheritance namespace biological process def The distribution of mitochondria including the mitochondrial genome into daughter cells after mitosis or meiosis mediated by interactions between mitochondria and the cytoskeleton PMID 10873824 PMID 11389764 SGD mcc is a GO 0048308 organelle inheritance is a GO 0048311 mitochondrion distribution Term id GO 0000002 name mitochondrial genome maintenance namespace biological process def T
13. is preserved by saving to and loading from GML Visual attributes specified in a GML file will result in a new visual style named Filename style when that GML file is loaded COMMANDS Load and save network files using the File menu of Cytoscape Network files may also be loaded directly from the command line using the SIF format or g GML format options FOR EXAMPLE To load a sample molecular interaction network in SIF format use the menu File Load Network In the resulting file dialog box select the file sampleData galFiltered sif After a few seconds a small network of 331 nodes should appear in the main window To load the same interaction network as a GML use the menu File Load Network again In the resulting file dialog box select the file sampleData galFiltered gml Node and edge attribute files as well as expression data and extra annotation can be loaded as well 19 NODE NAMING ISSUES IN CYTOSCAPE Typically genes are represented by nodes and interactions or other biological relationships are represented by edges between nodes For compactness a gene also represents its corresponding protein Nodes may also be used to represent compounds and reactions or anything else instead of genes If a network of genes or proteins is to be integrated with Gene Ontology GO annotation or gene expression data the gene names must exactly match the names specified in the other data files We strongly en
14. more than the cost of performing this distribution 69 d If distribution of the work is made by offering access to copy from a designated place offer equivalent access to copy the above specified materials from the same place e Verify that the user has already received a copy of these materials or that you have already sent this user a copy For an executable the required form of the work that uses the Library must include any data and utility programs needed for reproducing the executable from it However as a special exception the materials to be distributed need not include anything that is normally distributed in either source or binary form with the major components compiler kernel and so on of the operating system on which the executable runs unless that component itself accompanies the executable It may happen that this requirement contradicts the license restrictions of other proprietary libraries that do not normally accompany the operating system Such a contradiction means you cannot use both them and the Library together in an executable that you distribute 7 You may place library facilities that are a work based on the Library side by side in a single library together with other library facilities not covered by this License and distribute such a combined library provided that the separate distribution of the work based on the Library and of the other library facilities is otherwise permit
15. of jar files p containing plugins or URL s to jar files 16 Property name Default Valid values Related value command line argument containing plugins e g JLD http server my plugin jar JLW JLL defaultWebBrowser A path to the web browser on your system This only needs to be specified if Cytoscape can t find the web browser on your system 5 Building and Storing Interaction Networks Cytoscape reads an interaction network in two ways from a simple interaction file SIF or sif format or from a standard format known as Graph Markup Language GML or gml format SIF specifies nodes and interactions only while GML stores additional information about network layout and allows network data exchange with a variety of other network display programs Typically SIF is used to import interactions when building a network for the first time since it is easy to create in a text editor or spreadsheet Once the interactions have been loaded and layout has been performed the network may be saved to and subsequently reloaded from GML format in future Cytoscape sessions Both SIF and GML are ASCII text files and you can edit and view them in a regular text editor Additionally GML is supported by some other network visualization tools SIF FORMAT The simple interaction format is convenient for building a graph from a list of interactions It also makes it easy to combine different interacti
16. size Visual Attributes Associated with Edges e Edge Color Edge Line Type The following options are available ee Edge Source Arrow The following options are available el Tv el Edge Target Arrow The following options are available 34 Mel iv jel ivi e Edge Label the text label for each edge e Edge Font edge font and size Global Visual Properties e Background Color For each visual attribute you can specify a default value or define a visual mapping Cytoscape currently supports three different types of visual mappers e Passthrough Mapper network attributes are passed directly through to visual attributes A passthrough mapper only works for node edge labels For example a passthrough mapper can draw the common gene name on all nodes e Discrete Mapper discrete network attributes are mapped to discrete visual attributes For example a discrete mapper can map all protein protein interactions to the color blue e Continuous Mapper continuous graph attributes are mapped to visual attributes Depending on the visual attribute there are two types of continuous mappers o continuous to continuous mapper for example you can map a continuous value 0 1 to a continuous color gradient red green or node font size 10 100 o continuous to discrete mapper for example all values below 0 are mapped to square nodes and all values a
17. terms of Sections 1 and 2 above provided that you accompany it with the complete corresponding machine readable source code which must be distributed under the terms of Sections 1 and 2 above on a medium customarily used for software interchange If distribution of object code is made by offering access to copy from a designated place then offering equivalent access to copy the source code from the same place satisfies the requirement to distribute the source code even though third parties are not compelled to copy the source along with the object code 5 A program that contains no derivative of any portion of the Library but is designed to work with the Library by being compiled or linked with it is called a work that uses the Library Such a work in isolation is not a derivative work of the Library and therefore falls outside the scope of this License However linking a work that uses the Library with the Library 68 creates an executable that is a derivative of the Library because it contains portions of the Library rather than a work that uses the library Th xecutable is therefore covered by this License Section 6 states terms for distribution of such executables When a work that uses the Library uses material from a header file that is part of the Library the object code for the work may be a derivative work of the Library even though the source code is not Whether this is tr
18. the palette contained in CytoPanel 1 is shown below Cytoscape Desktop File Edit Data Select Layout Visualization Plugins CytoPanels Help Filters Set atin Pe Rae d X x A Gg r E shape from the palette onto the canvas To connect two nodes with an edge drag and drop the arrow onto a node on the canvas then move the cursor over a second node and click the mouse canonicalName Welcome to Cytoscape 2 2 The Menus File The File menu contains most basic file functionality File Load for Ed loading a variety of file types File Save for saving File Help displays 2 a credits screen File Print allows printing File Export As allows ae aap i you to export to a file in a number of graphics formats such as PDF Export As Ctrl shif P File Exit closes all windows of Cytoscape and exits the program File New opens a New network for editing This menu item is 2 disabled until an editor is chosen using the File SetEditor menu item Edit The Edit menu contains Undo and Redo menu items which undo mm SUAM Zig Data Select Layout Visualization Plu and redo edits made in the Attribute Browser The menu also gua E contains a Squiggle feature that enables you to mark up your Redo iagl network This can be particularly useful during live presentations a TER There are also options for creating and destroying view
19. work based on the Library the recipient automatically receives a license from the original licensor to copy distribute link with or modify the Library subject to these terms and conditions You may not impose any further restrictions on the recipients exercise of the rights granted herein You are not responsible for enforcing compliance by third parties with this License 70 11 If as a consequence of a court judgment or allegation of patent infringement or for any other reason not limited to patent issues conditions are imposed on you whether by court order agreement or otherwise that contradict the conditions of this License they do not excuse you from the conditions of this License If you cannot distribute so as to satisfy simultaneously your obligations under this License and any other pertinent obligations then as a consequence you may not distribute the Library at all For example if a patent license would not permit royalty free redistribution of the Library by all those who receive copies directly or indirectly through you then the only way you could satisfy both it and this License would be to refrain entirely from distribution of the Library If any portion of this section is held invalid or unenforceable under any particular circumstance the balance of the section is intended to apply and the section as a whole is intended to apply in other circumstances It is not the purpose of this section to ind
20. 20 2 Oi Nodes 331 0 selected Edges 362 0 selected Welcome to Cytoscape 2 2 Figure Using the Sample2 Visual Style Gene expression values are now displayed along a red green color gradient Visual Attributes Graph Attributes and Visual Mappers The Cytoscape Visual Mapper has three core components visual attributes network attributes and visual mappers e A visual attribute is any visual setting that can be applied to your network For example you can change all nodes to squares by setting the node shape visual attribute e Anetwork attribute is any attribute associated with a node or an edge For example each edge in a network may be associated with a label such as pd protein DNA interactions or pp protein protein interactions 33 e A visual mapper maps network attributes to visual attributes For example a visual mapper can map all protein DNA interactions to the color blue and all protein protein interactions to the color red Cytoscape includes a large number of visual attributes These are summarized in the tables below Visual Attributes Associated with Nodes e Node Color e Node Border Color Node Border Type The following options are available 11110 11111 Node Shape The following options are available AES Node Size width and height of each node Node Label the text label for each node e Node Font node font and
21. BILITY AND FITNESS FOR A PARTICULAR PURPOSE THE ENTIRE RISK AS TO THE QUALITY AND PERFORMANCE OF THE LIBRARY IS WITH YOU SHOULD THE LIBRARY PROVE DEFECTIVE YOU ASSUM E COST OF ALL NECESSARY SERVICING REPAIR OR CORRECTION 53 LAW OR AGREED TO IN ER PARTY WHO MAY MODIFY ITTED ABOVE BE LIABLE TO YOU CIAL INCIDENTAL OR ENTIAL DAMAGES ARISING OUT OF THE USE OR INABILITY TO USE THE Y INCLUDING BUT NOT LIMITED TO LOSS OF DATA OR DATA BEING RENDERED INACCURATE OR LOSSES SUSTAINED BY YOU OR THIRD PARTIES OR A FAILURE OF THE LIBRARY TO OPERATE WITH ANY OTHER SOFTWARE EVE IF SUCH HOLDER OR OTHER PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES 16 IN NO EVENT UNLESS REQUIRED BY APPLICABLI WRITING WILL ANY COPYRIGHT HOLDER OR ANY OTH M AND OR REDISTRIBUTE THE LIBRARY AS PER FOR DAMAGES INCLUDING ANY GENERAL SP CONSEQU LIBRA V N 2 END OF TERMS AND CONDITIONS 72
22. Cytoscape Cytoscape Window When you succeed in launching Cytoscape a window will appear that looks like this Cytoscape Desktop ID 9 4 ett 8 OX 8 Oe Select Attributes Create New Attribute Welcome to Cytoscape 2 2 3 Quick Tour of Cytoscape When a network is loaded Cytoscape will look something like the image below cytoscape Desktop File Edit Data Select Layout Visualization Plugins CytoPanels Help Filters Abr X x ee CytoPanel 1 Si F gaFitered sif fe Network i galFiltered sif CytoPanel 2 Node Attribute Browser Select Attributes Create New Attribute ID canonicalName species o4 YHROS4W YHROS4W Saccharomyces cerevisiae YDR461W YDR461W Saccharomyces cerevisiae A 1145 YNL145W Saccharomyces cerevisiae 57 YFL026W YFL026W Saccharomyces cerevisiae Node Attribute Browser Welcome to Cytoscape 2 2 The main window here has several components 1 The menu bar at the top See below for more information about each menu 2 The toolbar which contains icons for commonly used functions These functions are also available via the menus Hover the mouse pointer over an icon and wait momentarily for a description to appear as a tooltip 3 The network management panel top left This contains an optional network overview pane bottom left overview
23. Cytoscape 2 2 User Manual Nov 2005 The Cytoscape Collaboration The Cytoscape project is an ongoing collaboration between University of California at San Diego Institute for Systems Biology Institut D Memorial Sloan Kettering Cancer Center Funding for Cytoscape is provided by a federal grant from the U S National Institute of General Medical Sciences NIGMS of the National Institutes of Health NIH under award number GM070743 01 Corporate funding is provided through a contract from Unilever PLC amen Table of Contents 4 COMMAND LINE ARGUMENTS AND PROPER TIES 14 5 BUILDING AND STORING INTERACTION NETWOR K S 17 6 LOADING GENE EXPRESSION DATA 21 7 NODE AND EDGE 5 0 0 00 23 8 NAVIGATION AND LAYOUT A 3 27 INTRODUCTION TO VISUAL STYLES ccccsssscccccceesessseeeccceccessssceeecceesensseeeesceeseesssseeeececeecessaeeesceceeessseeeeeceeesssaeeeees VISUAL ATTRIBUTES GRAPH ATTRIBUTES AND VISUAL MAPPERS TUTORIAL CREATING A NEW VISUAL 5 2 1 220202020220 10 10000000000000000000000000000000000000 TUTORIAL CREA
24. Deselect All Nodes and Edges Ctrl Alt Shift A 10 Layout The Layout menu has an array of features for organizing the network visually according to one of several algorithms aligning and rotating groups of nodes and adjusting the size of the network Most of these Visualization Plugins Cyto Apply Spring Embedded Layout gt Rotate Scale Network Ali features are available from plugins that are packaged with Cytoscape ped 2 2 Apply Hierarchical Layout Visualization The Visualization menu provides options for changing the mapping from biological data to a visual representation colors of nodes Plugins CytoPanels Toggle Overview thickness of edges etc These features are explored in depth in CIEE section on visual styles This menu also provides an Overview of Set Visual Style your entire network which is helpful for navigating very large Disable Visual Mapper networks Plugins The Plugins menu has menu items or choices added by plugins that have been loaded such as Import BioPAX Document from file 11 12 CytoPanels Help Filters Import BioPAX Document from file Import BioPAX Document from URL Search cPath CytoPanels CytoPanels are floatable dockable panels which cut down on the number of pop up windows within Cytoscape The CytoPanels menu allows you to show or hide CytoPanel 1 CytoPanel 2 or CytoPanel 3 based on the menu item selected Note
25. ENSE ERMS AND CONDITIONS FOR COPYING DISTRIBUTION AND MODIFICATION H 0 This License Agreement applies to any software library or other program which contains a notice placed by the copyright holder or other authorized party saying it may be distributed under the terms of 66 this Lesser General Public License also called this License Each licensee is addressed as you A library means a collection of software functions and or data prepared so as to be conveniently linked with application programs which use some of those functions and data to form executables The Library below refers to any such software library or work which has been distributed under these terms A work based on the Library means either the Library or any derivative work under copyright law that is to say a work containing the Library or a portion of it either verbatim or with modifications and or translated straightforwardly into another language Hereinafter translation is included without limitation in the term modification Source code for a work means the preferred form of the work for making modifications to it For a library complete source code means all the source code for all modules it contains plus any associated interface definition files plus the scripts used to control compilation and installation of the library Activities other than copying distribution and modification are no
26. TING A NEW VISUAL STYLE WITH A DISCRETE 1 2 1 001 60100000000 38 TUTORIAL VISUALIZING EXPRESSION DATA ON A 41 22 22 2 020006000000000000000000000000 0050808080 39 NEW ONTOLOGY AND ANNOTATION 5 aaa qa awa 45 GENE ONTOLOGY SERVER WIZARD APPENDIX A OLD ANNOTATION SERVER FORMAT A 56 GENE ONTOLOGY SERVER WIZARD cccccccsssscssccsccesecececececececececececececesccecccacecececesacccecccecececceecececacccececcsecceccccececececs 56 BUILDING YOUR OWN ANNOTATION FILES eene n ne nen nene tettere ree nnn nnn n ananas sns nasa sanas nsns as nasa sanas nsns asas asas asa 57 LOAD DATA INTO 088 59 GETTING AND REFORMATTING GO DATA 59 APPENDIX B GNU LESSER GENERAL PUBLIC LICENSE 65 1 Introduction Cytoscape is an open source community software project for integrating biomolecular interaction networks with high throughput expression data and other molecular state information for visualization and analysis Although applicable to any system of molecular components and interactio
27. al circumstances For example on rare occasions there may be a special need to encourage the widest possible use of a certain library so that it becomes a de facto standard To achieve this non free programs must be allowed to use the library A more frequent case is that a free library does the same job as widely used non fr libraries In this case there is little to gain by limiting the free library to free software only so we use the Lesser General Public License In other cases permission to use a particular library in non free programs enables a greater number of people to use a large body of free software For example permission to use the GNU C Library in non free programs enables many more people to use the whole GNU operating system as well as its variant the GNU Linux operating system Although the Lesser General Public License is Less protective of the users freedom it does ensure that the user of a program that is linked with the Library has the freedom and the wherewithal to run that program using a modified version of the Library The precise terms and conditions for copying distribution and modification follow Pay close attention to the difference between a work based on the library and a work that uses the library The former contains code derived from the library whereas the latter must be combined with the library in order to run GNU LESSER GENERAL PUBLIC LIC
28. bove 0 are mapped to circular nodes However there is no way to smoothly morph between circular nodes and square nodes The matrix below shows visual mapper support for each visual property 35 E 2 5 L E se 8 EA 28 585 ES amp gt 2 O Node Properties Node Color x x Node Border Color X X Node Border Type X Node Shape X o Node Size X X Node Label X X o Node Font Family X o Node Font Size x x Edge Properties Edge Color x x Edge Line Type X Edge Source Arrow X o Edge Target Arrow X Edge Label x x o Edge Font Family X Edge Font Size x x Legend Mapping is not supported for specified visual property X Mapping is fully supported for specified visual property Mapping is partially supported for specified visual property Support for continuous to continuous mapping is not supported Tutorial Creating a New Visual Style To create a new visual style select Visualization gt Set Visual Properties from the main menu or select sua Ser the color wheel icon in the main button bar You will default 1 Define now see a new Visual Styles dialog box shown at Poa right 36 Visual Property Categories Click the New button and enter a name for your new visual style when prompted Then cl
29. cal names when you run Cytoscape For budding yeast it is much easier the yeast community always uses standard ORF names and so Cytoscape uses these as canonical names For human proteins and genes there is no such single simple standard See section 5 Building and Storing Interaction Networks for more information The solution for those working with human genes or proteins is once you have downloaded the annotations file to 1 Decide which naming system you want to use Download ftp ftp ebi ac uk pub databases GO goa HUMAN xtefs goa This cross reference file when used strategically allows you to create Cytoscape compatible annotation files in which the canonical name is the one most meaningful to you Examine xrefs goa to figure out which column contains the names you wish to use Make a very slight modification to the python script described below and then 5 Run that script supplying both xrefs goa and that annotation file as arguments Here are a few sample lines from xrefs goa SP 000115 00010348 ENSP00000222219 NP_001366 BAA28623 AAC77366 AAC35751 AAC39852 BAB55598 AAB51172 AAH10419 2960 DNASE2 1777 DNASE2 SP 000116 00010349 ENSP00000324567 ENSP00000264167 NP 003650 CAA70591 327 AGPS 8540 AGPS SP 000124 1 100010353 ENSP00000265616 ENSP00000322580 NP 005662 BAA18958 BAA18959 AAH20694 7993 D8S2298E Note that line wrapping has occurred here each line in this example
30. cape version 2 2 contains several new features plus improvements in the performance and usability of the software These include e Enhanced support for node and edge attribute handling including a powerful new attribute browser for navigating defining and editing node and edge attributes For plugin coders this also includes a greatly improved API cytoscape data CyAttributes e Support for dockable tabbed panels CytoPanels A set of Cytoscape editors for building and modifying networks interactively by adding nodes and edges to a drawing canvas Improved support for ontologies and other structured annotations Simplified mechanism for saving Visual Styles in between sessions A new GML visual style to manage visual properties from GML files Many performance improvements and bug fixes 2 Launching Cytoscape Cytoscape is a Java application that runs on Linux Windows and Mac OS X System requirements The system requirements for Cytoscape depend on the size of the networks the user wants to load view and manipulate We recommend a recent computer 1GHz CPU or higher with a high end graphics card and at least 512MB of free physical RAM Cytoscape expects a minimum screen resolution of 1024x768 There are a number of options for downloading and installing Cytoscape e For Windows and Linux platforms one step installation is available via InstallAnywhere For one step installation go to http www cytoscape org click Dow
31. clude the copyright notice for the Library among them as well as a reference directing the user to the copy of this License Also you must do one of these things a Accompany the work with the complete corresponding machine readable source code for the Library including whatever changes were used in the work which must be distributed under Sections 1 and 2 above and if the work is an executable linked with the Library with the complete machine readable work that uses the Library as object code and or source code so that the user can modify the Library and then relink to produce a modified executable containing the modified Library It is understood that the user who changes the contents of definitions files in the Library will not necessarily be able to recompile the application to use the modified definitions b Use a suitable shared library mechanism for linking with the Library A suitable mechanism is one that 1 uses at run time a copy of the library already present on the user s computer system rather than copying library functions into the executable and 2 will operate properly with a modified version of the library if the user installs one as long as the modified version is interface compatible with the version that the work was made with C Accompany the work with a written offer valid for at least three years to give the same user the materials Specified in Subsection 6a above for a charge no
32. columns can be omitted if your data doesn t include significance measures Every remaining row specifies the values for a gene starting with the formal name of the gene then a common name then the ratios then the significance values Some variations on this basic format are recognized see the formal file format specification below for more information Expression data files commonly have the file extensions mrna or pvals and these file extensions are recognized by Cytoscape when browsing for data files COMMANDS Load an expression data file using the File menu of Cytoscape or by specifying the filename using the e option at the command line The x command line option indicates that the expression data should not be loaded into node attributes This is an advanced option and is typically only used when the number of expression conditions is sufficiently large that it becomes unwieldy in the normal user interface FOR EXAMPLE Load a sample gene expression data set using the menu File Load Expression Matrix File In the resulting file dialog box select the file sampleData galExpData pvals As described in the following sections Cytoscape is now ready to integrate these data with the underlying molecular interaction network Detailed file format Advanced users In all expression data files any whitespace spaces and or tabs is considered a delimiter between adjacent fields Every line of text is either the header l
33. courage naming genes and proteins by their systematic ORF name or standard accession number common names may be displayed on the screen for ease of interpretation so long as these are available to the program in the annotation directory or in a node attribute file Cytoscape ships with all yeast ORF to common name mappings in a synonym table within the annotation directory Other organisms will be supported in the future Why do we recommend using standard gene names All of the external data formats recognized by Cytoscape provide data associated with particular names of particular objects For example a network of protein protein interactions would list the names of the proteins and the attribute and expression data would likewise be indexed by the name of the object The problem is in connecting data from different data sources that don t necessarily use the same name for the same object For example genes are commonly referred to by different names including a formal location on the chromosome identifier and one or more common names that are used by ordinary researchers when talking about that gene Additionally database identifiers from every database where the gene is stored may be used to refer to a gene e g protein accession numbers from Swiss Prot If one data source uses the formal name while a different data source used a common name or identifier then Cytoscape must figure out that these two different names really refer to the sam
34. d edges Control clicking at a position on the canvas creates a node at that position The NODE_TYPE attribute of the node will be the same as the NODE TYPE of the node most recently added defaulting to DefaultNode type In this manner you can use control clicking as a kind of stamp to add multiple nodes of the same type to the network Control clicking on a node on the canvas starts an edge with source at that node Move the cursor and a rubber banded line follows the cursor As the cursor passes over another node that node is highlighted and the rubber banded line will snap to a connection point on that second node Control click the mouse again and the connection is established The EDGE TYPE attribute of the edge will be the same as the EDGE TYPE of the edge most recently added defaulting to DefaultEdge type You can abort the drawing of the edge by control clicking on an empty spot on the palette You can delete nodes and edges by selecting a number of nodes and edges then selecting the Edit gt Delete Selected Nodes and Edges menu item You can recover any nodes and edges deleted from a network by selecting the Edit 2 Restore Deleted Nodes and Edges menu item Note that this will restore all nodes and edges that were previously deleted from the network not just those deleted by the most recent delete operation 11 CytoPanels What are CytoPanels CytoPanels are floatable dockable panels designed to cut down on the number of po
35. define other types of relationships e g geneFusion cogInference pullsDown activates degrades inactivates inhibits phosphorylates upRegulates Delimiters Whitespace space or tab is used to delimit the names in the simple interaction file format However in some cases spaces are desired in a node name or edge type The standard is that if the file contains any tab characters then tabs are used to delimit the fields and spaces are considered part of the name If the file contains no tabs then any spaces are delimiters that separate names and names cannot contain spaces If your network unexpectedly contains no edges and node names that look like edge names it probably means your file contains a stray tab that s fooling the parser On the other hand if your network has nodes whose names are half of a full name then you probably meant to use tabs to separate node names with spaces Networks in simple interactions format are often stored in files with a sif extension and Cytoscape recognizes this extension when browsing a directory for files of this type GML FORMAT In contrast to SIF GML is a rich graph format language supported by many other network visualization packages The GML file format specification is available at http www infosun fmi uni passau de Graphlet GML It is generally not necessary to modify the content of a GML file directly Once a network is built in SIF format and then laid out the layout
36. do these things To protect your rights we need to make restrictions that forbid distributors to deny you these rights or to ask you to surrender these rights These restrictions translate to certain responsibilities for you if you distribute copies of the library or if you modify it For example if you distribute copies of the library whether gratis or for a fee you must give the recipients all the rights that we gave you You must make sure that they too receive or can get the source code If you link other code with the library you must provide complete object files to the recipients so that they can relink them with the library after making changes to the library and recompiling it And you must show them these terms so they know their rights We protect your rights with a two step method 1 we copyright the library and 2 we offer you this license which gives you legal permission to copy distribute and or modify the library To protect each distributor we want to make it very clear that there is no warranty for the free library Also if the library is modified by someone else and passed on the recipients should know that what they have is not the original version so that the original author s reputation will not be affected by problems that might be introduced by others 65 Finally software patents pose a constant threat to the existence of any free program We wish to make sure that a company cannot ffect
37. e biological entity Cytoscape has two strategies for dealing with this naming issue one simple and one more complex The simple strategy is to assume that every data source uses the same set of names for every object If this is the case then Cytoscape can easily connect all of the different data sources To handle data sources with different sets of names as is usually the case when manually integrating gene information from different sources Cytoscape needs a data server that provides synonym information See 2 Annotation A synonym table gives a canonical name for each object in a given organism and one or more recognized synonyms for that object Note that the synonym table itself defines what set of names are the canonical names For example in budding yeast the ORF names are commonly used as the canonical names If a synonym server is available then by default Cytoscape will convert every name that appears in a data file to the associated canonical name Unrecognized names will not be changed This conversion of names to a common set allows Cytoscape to connect the genes present in different data sources even if they have different names as long as those names are recognized by the synonym server 20 For this to work Cytoscape must also be provided with the species to which the objects belong since the data server requires the species in order to uniquely identify the object referred to by a particular name This is usuall
38. edge on its palette This editor will define the nodes and shapes on its palette using the current Visual Style e aSimpleBioMoleculeEditor which defines the nodes and shapes on its palette using the SimpleBioMolecule Visual Style e aSimpleBioPAX Editor defines the nodes and shapes on its palette using a Visual Style that maps node shapes and colors according to the value of the 40 BIOPAX_NODE_TYPE attribute and maps edge target arrows according to the value of the BIOPAX_EDGE_TYPE attribute Note that in this version of Cytoscape the SimpleBioPAX_Editor is not a fully functional BioPAX editor but rather serves as an example Moreover there is no facility for output to BioPAX format in the current version of Cytoscape A fully functional BioPAX editor with output to BioPAX format is planned for a future version of Cytoscape When you bring up an editor the visual style for the current network view is set to the visual style that is associated with the editor If there is no current view at the time you make the File gt Set Editor then a new network and view and network will be created automatically for you To start editing a new network use the File gt New gt Network menu item The figure below shows the display for the DefaultCytoscapeEditor 101 xl File Edit Data Select Layout Visualization Plugins CytoPanels Help Filters amp bt OX A CytoPanel 1 K Network Editor C
39. eenshot above there are 5 columns total including the ID Most attribute values can be edited by double clicking an attribute cell list values cannot be edited and neither can the ID Attribute rows in the browser can be sorted alphabetically by specific attribute by clicking on a column heading A new attribute can be created using the Create New Attribute button Attributes created using the attribute browser must be one of four types integer string floating point or boolean The right click menu on the Attribute Browser has several functions This menu is useful for exporting attribute information to spreadsheet applications For example choose Select All and then Copy from the right click and then paste into a spreadsheet application 26 8 Navigation and Layout BASIC FEATURES Use the zooming buttons located on the toolbar to zoom in out of the interaction network shown in the current network display Zoom icons are detailed below te From Left to Right Zoom Out Zoom In Zoom Selected Region Zoom out to Display all of Current Network You can also zoom in out by holding down the right mouse button and moving the mouse to the right zoom in or left zoom out Use the left mouse button to select a node hold down the Shift key to select more than one node Use the right mouse button to launch a context sensitive menu with additional information about the node that was clicked
40. etwork view window The palette contains a set of shapes for nodes and arrows for edges The shapes on the palette are defined by the current Visual Style with Node Shape and Node Color mapping into the shape and color of a node and Edge Target Arrow mapping into the target arrow of an edge An example of an editor with the palette contained in CytoPanel 1 is shown below Cytoscape Desktop D x Fie Edit Data Select Layout Visualization Plugins CytoPanels Help Filters COS gt e Qo X Al CytoPanel 1 uu 2 Network Editor Cytoscape Editor To add a node to a network drag and drop a shape from the palette onto the canvas To connect two nodes with an edge drag and drop the arrow onto a node on the canvas then move the cursor over a second node and click the mouse Directed Edge gt l Protein Catalysis Nodes 5 0 selected Edges 4 0 selected CytoPanel 2 Node Attribute Browser Small Molecule Select Attributes Create New Attribute ID canonicalName species Biochemical Reaction Node Attribute Browser Edge Attribute Browser Welcome to Cytoscape 2 2 To bring up an editor use the File gt Set Editor menu item In Cytoscape 2 2 you are given a choice of three editors e aDefaultCytoscapeEditor which contains one default node and one default
41. f tabs equal to the number of conditions followed by the LamBpas token This format specifies both ratios and significance values Each line after the first is a data line with the following format FormalGeneName CommonGeneName ratiol ratio2 lambdal lambda2 numSigConds The first two tokens are gene names The names in the first column are the keys used for node name lookup these names should be the same as the names used elsewhere in Cytoscape i e in the SIF or GML files Traditionally in the gene expression microarray community who defined these file formats the first token is expected to be the formal name of the gene in systems where there is a formal naming scheme for genes while the second is expected to be a synonym for the gene commonly used by biologists although Cytoscape does not make use of the common name column The next columns contain floating point values for the ratios followed by columns with the significance values if specified by the header line The final column if specified by the header line should contain an integer giving the number of significant conditions for that gene Missing values are not allowed and will confuse the parser For example using two consecutive tabs to indicate a missing value will not work the parser will regard both tabs as a single delimiter and be unable to parse the line correctly Optionally the last line of the file may be a special footer line with the following format
42. files and expression data g graph lt GML network filename xxx gml Loads a network file in GML format see section on Building and Storing Interaction Networks i interaction lt SIF interactions filename gt yyy sif Loads a network file in SIF format see section on Building and Storing Interaction Networks b BDS bioDataServer bioData directory e g annotation manifest Specifies which directory to use for the BioDataServer annotations e expression lt expression filename gt zzz pvals Loads an expression data file see section on Loading Gene Expression Data n nodeAttributes lt nodeAttributes filename gt one or more 14 Loads node attributes files see section on Node and Edge Attributes j edgeAttributes lt edgeAttributes filename gt one or more Loads edge attributes files see section on Node and Edge Attributes s species Set the default species name c noCanonicalization Turn off default node name canonicalization h help help Help display these command line arguments p plugin JLD JLW JLL Specify a list of plugins jar files directories containing plugins URLs http to jar files or URLs to manifest files listing jar files props lt properties file gt specify and load a properties file usually named cytoscape props vprops vp vizprops lt properties file gt specify and load a visual mapping properties file usually
43. guishing version number If the Library specifies a version number of this License which applies to it and any later version you have the option of following the terms and conditions either of that version or of any later version published by the Free Software Foundation If the Library does not specify a license version number you may choose any version ever published by the Free Software Foundation 14 If you wish to incorporate parts of the Library into other free programs whose distribution conditions are incompatible with these write to the author to ask for permission For software which is copyrighted by the Free Software Foundation write to the Free Software Foundation we sometimes mak xceptions for this Our decision will be guided by the two goals of preserving the free status of all derivatives of our free software and of promoting the sharing and reuse of software generally NO WARRANTY 71 15 BECAUSE THE LIBRARY IS LICENSED FREE OF CHARGE THERE IS NO WARRANTY FOR THE LIBRARY TO THE EXTENT PERMITTED BY APPLICABLE LAW EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT HOLDERS X T AND OR OTHER PARTIE OVIDE THE LIBRARY AS IS WITHOUT WARRANTY OF ANY KIND EITHER EXPRESSED OR IMPLIED INCLUDING BU OT LIMITED TO THE R D IMPLIED WARRANTIES OF MERCHANTA
44. he maintenance of the structure and integrity of the mitochondrial genome GO ai is a GO 0007005 mitochondrion organization and biogenesis gene association sgd annotation file for yeast SGD 5000003916 AAD10 GO 0006081 SGD_REF S000042151 PMID 10572264 155 aryl alcohol dehydrogenase putative YJR155W gene taxon 4932 20020902 SGD SGD 5000005275 AAD14 GO 0008372 SGD_REF S000069584 ND C aryl alcohol dehydrogenase putative YNL331C gene taxon 4932 20010119 SGD Gene Ontology Server Wizard The Gene Ontology Server Wizard is a new graphical user interface used to select ontology and annotation files By following the wizard you do not have to write manifest files which were used in older versions of Cytoscape to specify the file location of the ontology and gene annotation files 46 Step 1 Select Data Format Gene Ontology Wizard Welcome to the Gene Ontology Wizard Which file Format do you want to load Cytoscape BioDataServer anno and onto Note Please put all data files both annotation and ontology in the same directory Otherwise the Gene Ontology Wizard cannot load the files Press the Next button to continue e 9 In this panel you can select two types of data formats Cytoscape BioDataServer or Gene Ontology Select Gene Ontology to use the new formats obo and gene association files If you want to use the old file formats select Cytoscape BioDataServer A description of how
45. here is no filter currently selected To edit a filter select it from the Available filters list If the list is empty you can create a new filter with the Create new filter button Create new filter Remove Available Filters Node null 0 0 Edge null 0 0 If the first filter is selected then the dialog looks as shown without the colors Numeric Attribute Filter Create new filter Remove selected filter Filter Name Node null 0 0 Select graph objects of type Node Node null 0 0 Edge null 0 0 4 with a value for numeric attribute that is H 0 0 Apply selected filter As for the colors The Purple Box An existing or newly created filter can be edited in this area Each filter type has its own user interface for editing The Orange Box All available filters are shown in this list Initially this list will contain sample filters but as you create more they will be added here The Cyan Box Pressing Create new filter adds a filter to the Available Filters box and Remove selected filter deletes the currently selected filter Creating Filters The Create new filter button brings up the Filter creation dialog box shown below 51 Filter types Filter Type Description Numeric Filter Select nodes or edges based on the value of a String Filter text attribute Topology Filter Boolean Meta N
46. ick the Define button You will now see pw the main Visual Styles Properties dialog box shown at right Edas sime etes Node Label Node Font Node Label Color Node Border Type Node Shape Node Size Node Color Node Border Color Default e Change Default From this dialog box you can flip between Node Attributes Edge Attributes and Global Defaults You can also specify default values for any visual property or define a new custom Mapping mapping Duplicate Delete J For example to set the default node shape to triangles select Create a new mapper Node Attributes gt Node Shape Then click the Change Default button and select the Triangle icon from the selection list Apply to Network 1 Close Applying Changes to the Network To apply your visual style to your network hit the Apply to Network button available in the bottom of the dialog panel Saving a Visual Style When you exit Cytoscape new visual styles or newly modified visual styles will automatically be saved in the vizmap props file You can therefore create a new visual style and apply it to all future networks 37 Tutorial Creating a New Visual Style with a Discrete Mapper Set Visual Style es Edge Attributes Global Defaults The following tutorial demonstrates how to create a new visual style with a discrete mapper The goal is to draw Protein DNA
47. ine or contains all the measurements for a particular gene No name conversion is applied to expression data files The names given in the first column of the expression data file should match exactly the names used elsewhere i e in SIF or GML files The first line is a header line with one of the following three formats text text condl 42 condl cond2 NumSigConds text text condl cond2 lt tab gt lt tab gt RATIOS lt tab gt lt tab gt LAMBDAS The first format specifies that both expression ratios and significance values are included in the file The first two text tokens contain names for each gene The next token set specifies the names of the experimental conditions these columns will contain ratio values This list of condition names must then be duplicated exactly each spelled the same way and in the same order Optionally a final column with the title NumSigconds may be present If present this column will contain integer values indicating the number of conditions in which each gene had a statistically significant change according to some threshold 22 The second format is similar to the first except that the duplicate column names are omitted and there is nO NumSigConds fields This format specifies data with ratios but no significance values The third format specifies an MTX header which is a commonly used format Two tab characters precede the RATIOS token This token is followed by a number o
48. iption GO 45449 regulation of transcription Cytoscape can use this hierarchical ontology to annotate recognized genes if the user chooses a level of the hierarchy to use for a given set of annotations The ontology provided to Cytoscape does not have to be hierarchical but if it is not there is no real advantage to storing annotations this way compared to just storing the annotation terms in a node attribute file The Gene Ontology Server originally called the biodata server is a Cytoscape feature which allows you to load navigate and assign annotation terms to nodes in a network In version 2 2 Cytoscape has a new feature called the Gene Ontology Server Wizard which enables users to select a local ontology and annotation files from the user interface Although 2 2 is backwards compatible with the old file formats the manifest file which includes a list of anno annotation and onto ontology files we strongly suggest using the new file formats See Appendix B for a description of how the old file formats can be created and used New Ontology and Annotation Files The standard file formats used in this release are OBO and gene association The GO website details these file formats e Ontologies and Definitions http www geneontology org GO downloads shtml ont e Current Annotations http www geneontology org GO current annotations shtml Cytoscape provides a copy of the Gene_ontology obo text file in the annotation directory
49. ird parties under the terms of this License d If a facility in the modified Library refers to a function or a table of data to be supplied by an application program that uses the facility other than as an argument passed when the facility is invoked then you must make a good faith effort to ensure that in the event an application does not supply such function or table the facility still operates and performs whatever part of its purpose remains meaningful For example a function in a library to compute square roots has 67 a purpose that is entirely well defined independent of the application Therefore Subsection 2d requires that any application supplied function or table used by this function must be optional if the application does not supply it the square root function must still compute square roots These requirements apply to the modified work as a whole If identifiable sections of that work are not derived from the Library and can be reasonably considered independent and separate works in themselves then this License and its terms do not apply to those sections when you distribute them as separate works But when you distribute the same sections as part of a whole which is a work based on the Library the distribution of the whole must be on the terms of this License whose permissions for other licensees extend to the entire whole and thus to each and every part regardless of who wrote it Th
50. ively restrict the users of a free program by obtaining a restrictive license from a patent holder Therefore we insist that any patent license obtained for a version of the library must be consistent with the full freedom of use specified in this license Most GNU software including some libraries is covered by the ordinary GNU General Public License This license the GNU Lesser General Public License applies to certain designated libraries and is quite different from the ordinary General Public License We use this license for certain libraries in order to permit linking those libraries into non free programs When a program is linked with a library whether statically or using a shared library the combination of the two is legally speaking a combined work a derivative of the original library The ordinary General Public License therefore permits such linking only if the entire combination fits its criteria of freedom The Lesser General Public License permits more lax criteria for linking other code with the library We call this license the Lesser General Public License because it does Less to protect the user s freedom than the ordinary General Public License It also provides other free software developers Less of an advantage over competing non free programs These disadvantages are the reason we use the ordinary General Public License for many libraries However the Lesser license provides advantages in certain speci
51. l refer to a different or perhaps non existent edge The following is an example edge attributes file InteractionStrength YAL001C pp YBRO43W 0 82 YMRO22W pd YDL112C 0 441 YDL112C pd YMRO22W 0 9013 Cytoscape treats edge attributes as directional so note that the second and third edge attribute values refer to two different edges source and target are reversed though the nodes involved are the same Each attribute is stored in a separate file Node and edge attribute files use the same format Node attribute file names often use the suffix noa while edge attribute file names use the suffix eda Cytoscape recognizes these suffixes when browsing for attribute files Node and edge attributes may be loaded at the command line using the and j options or via the File Load menu When expression data is loaded using an expression matrix it is automatically copied into the Node Attributes data structure unless explicitly specified not to Detailed file format Advanced users Every attribute file has one header line that gives the name of the attribute and optionally some additional meta information about that attribute The format is as follows attributeName class formal class of value The first field is always the attribute name it cannot contain spaces If present the class field defines the formal package qualified name of the class of the attribute values For example java lang String for Stri
52. lation of the Cytoscape software is accomplished using the JnstallAnywhere product from ZeroG Software Inc http zerog com 55 Appendix A Old Annotation Server Format The following section is still valid however we strongly recommend using the new formats described in the previous section since they are easier to download directly from the Gene Ontology project and use directly Gene Ontology Server Wizard The Gene Ontology Server Wizard is a new graphical user interface used to select ontology and annotation files Step 1 Select Data Format Gene Ontology Wizard Welcome to the Gene Ontology Wizard Which file Format do you want to load jj Gene Ontology obo and gene association Note Please put all data files both annotation and ontology in the same directory Otherwise the Gene Ontology Wizard cannot load the files Press the Next button to continue e Next Cancel If you want to use the old manifest file to load annotations select Cytoscape BioDataServer Step 2 Specify Manifest File 56 Gene Ontology Wizard Manifest File should include both annotation and ontology files cytoscape v2 2 annotation manifest Select Manifest File Please press the Finish button to load BioDataServer If you selected Cytoscape BioDataServer in the first step you need to specify manifest file which lists ontology and annotation files to load Then click on finish AII da
53. le annotation file for yeast SGD S000004660 1 GO 0006839 SGD_REF S000050955 PMID 2167309 IGI SGD S000000126 P ADP ATP translocator YMRO56C gene taxon 4932 20040226 SGD The third element AACI called DB Object Symbol in the gene association format will be used as a node identifier and canonical name for the gene However some network files gal or sif instead use the 11 element YMROS6C the first entry in Synonym as a node identifier Since Cytoscape applies annotations based on these identifiers the identifiers in the network file and in DB Object Symbols must match This check box is used when you load network files that use the Synonym as the node identifier 48 Overwrite default species name menu If not specified species name for a network data will be overwritten by a property called defaultSpeciesName and the Gene Ontology Server will use it to choose which annotations to be applied You can change defaultSpeciesName from this list e Links to related web sites You can navigate to GO s Current Annotation and NCBI s Taxonomy pages from the links The links open the default web browser when clicked Once you have finished specifying the options click on finish The OBO file and gene_association files specified in this panel will be automatically loaded Note 1 The OBO file and gene_association files MUST be in the same directory and you must have write permission for the directory Note 2 Please make s
54. len ipiToNPHash print test s gt NP 054861 s tester ipiToNPHash tester bioproc open bioproc txt w molfunc open molfunc txt w cellcomp open cellcomp txt w bioproc write species s type Biological Process curator GO n species molfunc write species s type Molecular Function curator GO n species cellcomp write species s type Cellular Component curator GO n species lines open associationFilename read split n sys stderr write found d lines n len lines for line in lines if line find 0 or len line lt 2 continue tokens line split t goOntology tokens 8 goIDraw tokens 4 goID goIDraw split 1 ipiName fixCanonicalName tokens 10 if len ipiName 1 continue if not ipiToNPHash has key ipiName continue refseqName ipiToNPHash ipiName printName refseqName printName ipiName if ipiName tester print s s has go term s tester printName goID if goOntology C cellcomp write s s n printName goID elif goOntology P bioproc write elif goOntology molfunc write P sWMn printName goID 1 s n printName goID 64 Appendix B GNU Lesser General Public License GNU LESSER GENERAL PUBLIC LICENSE Version 2 1 February 1999 Copyright C 1991 1999 Free Software Foundation
55. less term s result else print result if len sys argv 2 print usage 55 lt someFile xml gt sys argv 0 sys exit inputFilename sys argv 1 print gt gt sys stderr reading s inputFilename text open inputFilename read print gt gt sys stderr read 54 characters 5 len text regex go term gt lt go term gt cregex pre compile regex re DOTALL matches newlines m pre findall cregex text print gt gt sys stderr number of go terms d len m regex2 lt go accession gt GO lt go accession gt lt go name gt lt go name gt cregex2 re compile regex2 re DOTALL regex3 lt go isa s rdf resource http www geneontology org go GO s gt cregex3 re compile regex3 re DOTALL regex4 lt go part of s rdf resource http www geneontology org go GO s gt cregex4 re compile regex4 re DOTALL goodElements 0 badElements 0 print curator GO type all for term in m m2 re search cregex2 term 62 if m2 goodElements 1 id m2 group 1 name m2 group 2 isaIDs m3 re findall cregex3 term for ref in m3 isaIDs append ref m4 re findall cregex4 term partofIDs for ref in m4 partofIDs append ref flatFilePrint id name isaIDs partofIDs else badElements 1 print gt gt sys stderr no match to m2 print gt gt sys stderzr
56. lor wheel in the main button bar menu Introduction to Visual Styles The Cytoscape distribution you have downloaded automatically loads several predefined visual styles to get you started when you start Cytoscape by using one of the cytoscape sh or cytoscape bat scripts see step 3 in section 2 Launching Cytoscape To demonstrate these styles try out the following example Load a sample network From the main menu select File gt Load gt Graph and select sampleData galFiltered sif e Layout the network select Layout gt yFiles gt Organic e Load a sample set of expression data From the main menu select File gt Load gt Expression Matrix File and select sampleData galExpData pvals By default the Visual Style labeled default will be automatically applied to your network This default style has a blue background circular pink nodes and blue edges see sample screenshot below 30 Cytoscape Desktop po File Edit Data Select Layout Visualization Plugins CytoPanels Help Filters Steere XOKAG Z 7 w M CytoPanel 1 galFiltered sif Network Nodes Edges 331 0 362 0 Nodes 331 0 selected Edges 362 0 selected Welcome to Cytoscape 2 2 Figure Using the default Visual Style 31 You can flip through different visual styles by making a selection from the Visual Style pull down menu For example if you select Sample1 a new vi
57. me nodes For example the following specifies three edges between the same pair of nodes two of type pp and one of type pa nodel pp node2 nodel pp node2 nodel pd node2 Edges connecting a node to itself self edges are also allowed nodel pp nodel Every node and edge in Cytoscape has an identifying name most commonly used with the node and edge data attribute structures Node names must be unique as identically named nodes will be treated as identical nodes The name of each node will be the name in this file by default unless another string is mapped to display on the node using the visual mapper This is discussed in the section on visual styles The name of each edge will be formed from the name of the source and target nodes plus the interaction type for example sourceName edgeTyp targetName The tag interaction type should be one of DD piece protein protein interaction 1575 protein gt DNA e g transcription factor binding upstream of a regulating gene Any text string will work but the above are the conventions that have been followed thus far Additional interaction types are also possible but not widely used e g protein gt reaction PO reaction gt compound GY P PE compound reaction Ql a d genetic lethal relationship 1S SEDE protein metabolite interaction Ipsos satur metabolite protein interaction 18 Even whole words or concatenated words may be used to
58. n Edge names are all of the form sourceName edgeType targetName Note that this format is different from the specification of interactions in the SIF file format To be explicit in a SIF file an interaction looks like sourceNam dgeType targetNam To set an attribute for the edge defined by this interaction the matching line in an attributes file should look like sourceName edgeType targetName valu Yes this is confusing we re planning on fixing this in the next file format update for Cytoscape To specify lists of values use the following syntax listAttributeName class java lang String firstObjectName firstValue secondValue thirdValue secondObjectName onlyOneValue This defines an attribute which is a list of Strings The first object has three strings and thus three elements in its list while the second object has a list with only one member In the case of a list every attribute value should be specified as a list and every member of the list should be of the same class Again the class will be inferred if it is not specified in the header line Lists are not supported by the visual mapper so can t be mapped to visual attributes Attribute Browser 25 When Cytoscape is started the Attribute Browser appears in the bottom Cytopanel This browser can be hidden and restored using the F5 key Like other Cytopanels the browser can be undocked by pressing the little icon in the browser
59. n order for the keyboard short cuts to work the Cytoscape Desktop must have the focus a Help Filte v CytoPanel 1 Ctrl 1 v CytoPanel 2 Ctrl 2 CytoPanel 3 Ctrl 3 In addition CytoPanels can be floated or docked by selected the icon at the top right corner of each CytoPanel The icon and Ful tooltip will change based on the CytoPanel state If the CytoPanel Finat Dock is docked clicking on the icon will float the CytoPanel as Window Window indicated by the Float Window tooltip Alternatively if the CytoPanel is floating clicking on the icon will dock the CytoPanel as indicated by the Dock Window tooltip 44 12 Annotation Annotations in Cytoscape are stored as a set of ontologies e g the Gene Ontology GO An ontology consists of a set of controlled vocabulary terms that annotate the genes for a given organism and a synonym table for gene names For example using the Gene Ontology the Saccharomyces Cerevisiae GAL4 gene s biological process is described as regulation of transcription to which GO has assigned the number 45449 a GO ID You can see below that regulation of transcription is a subcategory of transcription which is a subcategory of nucleobase nucleoside nucleotide and nucleic acid metabolism etc GO 8150 biological_process GO 7582 physiological processes GO 8152 metabolism GO 6139 nucleobase nucleoside nucleotide and nucleic acid metabolism GO 6350 transcr
60. named vizmap props noDialog suppressView Do not popup informational dialog when the expression file is loaded vt VT lt view threshold gt Specify the threshold of nodes at which views will not automatically be created script script lt script text end Specify script text rp resourcePlugin lt resource plugins gt Specify the list of resource plugins Note that most data sets may also be loaded after Cytoscape is running Additional command line arguments that are not recognized by the Cytoscape core are passed to the PlugIn modules Please refer to the documentation for each specific PlugIn for more details 15 Cytoscape Properties The Cytoscape Preferences Dialog accessed via Edit gt Preferences has sections for general properties display editing and plugins specification via the properties mechanism Preferences in Cytoscape are stored in the form of Java properties ec C Pref Edi specified in the cytoscape props file located in the e ea users working directory home directory called cytoscape and located in the users home bioDataServer PleaseSpecify n defaultSpeciesName PleaseSpecify directory or Cytoscape distribution directory This secondaryViewThreshold 2000 file is automatically loaded at startup time and s written upon normal exit of the application Add Cytoscape properties are displayed in the Properties
61. ngs java lang Double for floating point values java lang Integer for integer values etc If the value is actually a list of values the class should be the type of the objects in the list If no class is specified in the header line Cytoscape will attempt to guess the type from the first value If the first value contains numbers in a floating point format Cytoscape will assume java lang Double if the first value contains only numbers with no decimal point Cytoscape will assume java lang Integer otherwise Cytoscape will assume java lang String Note that the first value can lead Cytoscape astray for example 24 floatingPointAttribute firstName 1 secondName 2 5 In this case the first value will make Cytoscape think the values should be integers when in fact they should be floating point numbers It s safest to explicitly specify the value type to prevent confusion Every line past the first line identifies the name of an object and the String representation of the attribute value The delimiter is always an equals sign whitespace spaces and or tabs before and after the equals sign is ignored This means that your names and values can contain whitespace but object names cannot contain an equals sign and no guarantees are made concerning leading or trailing whitespace Usually the object names should be the same as the names in your graph file unless name conversion is being used see the section on name resolution in sectio
62. nload Cytoscape and follow the on screen instruction e For Mac OS X we provide an alternative installation available as a dmg zip file When installed via this method Cytoscape functions as a regular Mac application and can be accessed via your Applications folder e Finally you can download and install a compressed archive distribution Instructions for this option are provided below 1 Download and unpack the distribution Cytoscape is distributed as a compressed archive tar gz or zip containing the following files and directories cytoscape jar Main Cytoscape application Java archive cytoscape props User configurable properties and preferences vizmap props User configurable visual mapping preferences cytoscape sh Script to run Cytoscape from command line Linux Mac OS X cytoscape bat Script to run Cytoscape Windows LICENSE txt Cytoscape GNU LGPL License Cytoscape2 2Manual pdf Cytoscape 2 2 Manual the document you are reading now sampleData galFiltered gml Sample molecular interaction network file galFiltered sif Identical network in Simple Interaction Format galExpData pvals Sample gene expression matrix file BINDyeast sif Network of all yeast protein protein interactions in the BIND database as of Nov 2005 BINDhuman sif Network of all human protein protein interactions in the BIND database as of Nov 2005 yeastHighQuality sif Sample molecular interaction network file annotati
63. ns Cytoscape is most powerful when used in conjunction with large databases of protein protein protein DNA and genetic interactions that are increasingly available for humans and model organisms A software Core provides basic functionality to layout and query the network to visually integrate the network with expression profiles phenotypes and other molecular state information and to link the network to databases of functional annotations The Core is extensible through a plug in architecture allowing rapid development of additional computational analyses and features The central organizing metaphor of Cytoscape is a network graph with genes proteins and molecules represented as nodes and interactions represented as links i e edges between nodes Development Cytoscape is a collaborative project between the Institute for Systems Biology Dr Leroy Hood the University of California San Diego Dr Trey Ideker Memorial Sloan Kettering Cancer Center Dr Chris Sander and the Institut Pasteur Dr Benno Schwikowski Visit http www cytoscape org for more information License Cytoscape is protected under the GNU LGPL Lesser General Public License The License is included as an appendix to this manual but can also be found online http www gnu org copyleft lesser txt Cytoscape also includes a number of other open source libraries which are detailed in Section 10 Acknowledgements below What s New in 2 2 Cytos
64. ode Interacti Edge Interactic lt OK The important thing to realize when creating a filter is that the filter does not do anything by itself Once created the filter must be run String Filter Manage Filters r String Pattern Filter ee Create new filter Remove selected filter Filter Name ode canonicalName YDL r Available Filters Select graph objects of type Node Node null 0 0 SST Se Edge null 0 0 with a value for text attribute canonicalName E Node canonicalName YDL NodeTopology that matches the pattern YDL BooleanMeta Apply selected filter The String Filter allows you to filter nodes or edges by a given string node or edge attribute Attributes that are loaded on the network are available for filtering against Search terms are entered in the text box at the bottom For example to match any Node whose canonicalName starts with YDL you would select Node canonicalName and type YDL The is important as it matches any number of characters after YDL If you want to be more specific and only select nodes whose canonicalName starts with YDLOO followed by any other two characters you would type YDLO00 The 2 denotes any single character while the represents zero or more characters Full regular expression searching is supported although is not covered here Once the filter is defined it will be assigned a default desc
65. of the network 4 The main network view window which displays the network 5 The attribute browser panel bottom panel which displays attributes of selected nodes and edges and enables you to modify the values of attributes The network management and attribute browser panels are dockable tabbed panels known as CytoPanels You can undock any of these panels by clicking on the Float Window control in the upper right corner of the CytoPanel If you select this control e g on the attribute browser panel you will now two Cytoscape windows the main window and a new window labeled CytoPanel 2 similar to the one shown below io x Es Node Attribute Browser Select Attributes Create New Attribute ID canonicalName species YHR084W YHR084W Saccharomyces cerevisiae YDR461W YDR461W Saccharomyces cerevisiae YNL145W YNL145W Saccharomyces cerevisiae YFL026W YFL026W Saccharomyces cerevisiae 1 Node Attribute Browser Edge Attribute Browser Note that CytoPanel 2 now has a Dock Window control If you select this control the window will dock onto the main window Cytoscape also has a set of editors that enable you to build and modify networks interactively by dragging and dropping nodes and edges from a palette onto the main network view window The editors can be invoked using the Set Editor command on the File menu An example of a simple biomolecule editor with
66. on 27 NETWORK LAYOUT The Layout menu has an array of features for organizing the network visually according to one of several algorithms aligning and rotating groups of nodes and adjusting the size of the network Most of these features are available from plugins that are packaged with Cytoscape 2 2 Some of the layout algorithms provided with Cytoscape 2 2 are Cytoscape Spring embedded Layout Spring embedded layout is based on a force directed paradigm Network nodes are treated like physical objects that repel each other such as electrons The connections between nodes are treated like metal springs attached to the pair of nodes These springs repel or attract their end points according to a force function The layout algorithm sets the positions of the nodes in a way that minimizes the sum of forces in the network To lay out your network in Cytoscape using a Spring Embedded Layout select Layout gt Apply Spring Embedded Layout from the main menu A sample screen shot is provided below 28 yFiles Circular Layout This algorithm produces layouts that emphasize group and tree structures within a network It partitions the network by analyzing its connectivity structure and arranges the partitions as separate circles The circles themselves are arranged in a radial tree layout fashion yFiles Hierarchical Layout The hierarchical layout algorithm is good for representing main direction or flow within a net
67. on Directory containing Gene Ontology database entries currently for yeast only Info in this directory is used to associate gene names with synonyms as well as process function and cellular location data plugins Directory containing cytoscape PluglIns in jar format From Ideker et al Science 292 929 2001 Obtained from data hosted at http www blueprint org bind bind_downloads html From von Mering et al Nature 417 399 2002 and Lee et al Science 298 799 2002 2 If necessary install Java If not already installed on your computer download and install the Java 2 Runtime Environment version 1 4 2 or higher It can be found at http java sun com j2se 1 4 2 download html 3 Launch the application by running cytoscape sh from the command line Linux or Mac OS X or double clicking cytoscape bat Windows Alternatively you can pass the jar file to Java directly using the command java jar cytoscape jar In Windows it is also possible to directly double click the jar file to launch it However this does not allow specification of command line arguments such as the location of the annotation data directory see the section on command line arguments for details On Mac OS X users who downloaded the Mac OS X version of Cytoscape can double click on the Cytoscape icon to start Cytoscape Either double clicking or dragging onto the Cytoscape application icon any sif or gml file will load that file into
68. on sets into a larger network or add new interactions to an existing data set The main disadvantage is that this format does not include any layout information forcing Cytoscape to re compute a new layout of the network each time it is loaded Lines in the SIF file specify a source node a relationship type or edge type and one or more target nodes nodeA lt relationship type gt nodeB nodeC relationship type nodeA nodeD relationship type nodeE nodeF nodeB nodeG nodeY relationship type nodeZ A more specific example is 17 nodel typeA node2 node2 typeB node3 node4 node5 nodeO The first line identifies two nodes called node1 and node2 and a single relationship between 1 and node2 of type typea The second line specifies three new nodes node3 node4 and node5 here node2 refers to the same node as in the first line The second line also specifies three relationships all of type typeB and with node2 as the source with node3 node4 and node5 as the targets respectively This second form is simply shorthand for specifying multiple relationships of the same type with the same source node The third line indicates how to specify a node that has no relationships with other nodes This form is not needed for nodes that do have relationships since the specification of the relationship implicitly identifies the nodes as well Duplicate entries are allowed and indicate multiple edges between the sa
69. ou are interested in and click Download Let s use GO Annotations EBI Human as an example After you have downloaded and saved the file look at the first few lines SPTR 000115 DRN2_HUMAN GO 0003677 PUBMED 9714827 TAS F Deoxyribonuclease II precursor IPI00010348 protein taxon 9606 SPTR SPTR 000115 DRN2_HUMAN GO 0004519 GOA spkw IEA Deoxyribonuclease II precursor IPI00010348 protein taxon 9606 20020425 SPTR SPTR 000115 DRN2 HUMAN GO 0004531 PUBMED 9714827 TAS Deoxyribonuclease II precursor IPI00010348 protein taxon 9606 SPTR Note that line wrapping has occurred here so each line of the actual file is wrapped to two lines The goal is to create from these lines the following lines species Homo sapiens type Molecular Function curator GO 00010348 0003677 00010348 0004519 00010348 0004531 or species Homo sapiens type Biological Process curator GO NP_001366 0006259 NP_001366 0006915 NP_005289 0007186 NP_647593 0006899 60 The first sample contains molecular function annotation for proteins and each protein is identified by its IPI number IPI is the International Protein Index which maintains cross references to the main databases for human mouse and rat proteomes The second sample contains biological process annotation and each protein is identified by its NP RefSeq number These two naming systems IPI and RefSeq are two of many that you can use for canoni
70. p up windows within Cytoscape and to create a more unified user experience For example in Cytoscape 2 1 the cPath PlugIn enables users to click on a node and immediately view node details in a pop up window Now with CytoPanels we can now show these node details in an embedded CytoPanel The image below shows a screenshot of the latest BioPAX PlugIn When you click on a node the node details appear directly in the left CytoPanel 42 eee File Edit Data Select Layout Visualization Plugins CytoPanels Help 8 amp X X Nodes 168 1 selected Edges 291 0 selected 43 The user can then chose to resize hide or float the left CytoPanel For example in the screenshot below the user has chosen to float the CytoPanel Fre Edm Data Select Layout Visualization Plugins CyoPaae s Help Network RaPxw a j er d 02 Apogaoyr 3 Ow Basic Usage Cytoscape 2 2 includes three CytoPanels CytoPanel 1 appears on the left CytoPanel 2 appears on the bottom and CytoPanel 3 appears on the right By default only CytoPanel 1 will appear and it will automatically contain the network list and network Overview component The other panels may appear depending on the mix of PlugIns currently installed in your Cytoscape distribution CytoPanels can be shown or hidden by selecting the desired menu item within the CytoPanels menu or by entering the proper keyboard accelerator short cut i
71. reated Visual Style e In the Set Visual Properties Dialog box select Node Attributes Node Color e Click the New button in the mapping panel e You will be prompted to select a mapping type passthrough mapper discrete mapper or continuous mapper for an overview of the differences between these mappers please refer back to section 8 2 Select continuous mapper and enter a descriptive name For example enter ColorGradient e From the Map Attribute pull down menu select gall RGexp e Click the Add Point button twice to add two data points Set the first point to 1 Below Yellow Cytoscape Desktop Equal White File Edit Date Selec Layou Visualizatic Plugin CytoPane Helr Filter _ Z R i gt a to 2 Equal Red A d 22 x Al Click the Apply to Graph button galFiltered sif This visual mapper will set all nodes with a gallRGexp value less than 1 to Yellow and all nodes with a gallRGExp value greater than 2 to Black Additionally all values between 1 and 2 will be painted with a white red color gradient Sample screenshot is shown at right Nodes 331 0 selected Edges 362 0 selected Welcome to Cytoscape 2 2 39 10 Editing Networks Cytoscape has a set of editors that enable you to build and modify networks interactively by dragging and dropping nodes and edges from a palette onto the main n
72. riptive name Numerical Filter Manage Filters r Numeric Attribute Filter Create new filter Remove selected filter Filter Name Node gal RGexp 1 0 Available Filters Select graph objects of type Node 2 Node gallRGexp gt 1 0 aE gal4RGsig Edge null 0 0 with a value for numeric attribute PATES Node canonicalName YDL E 4 Jgal4RGexp NodeTopology that is gt NM 1 0 gal80Rsig BooleanMeta gal1RGsig gal80Rexp Apply selected filter 52 The Numerical Filter also allows you to filter nodes or edges and presents you with a list of available attributes This filter matches greater than less than or equal to a number you type in the search box Node Topology Filter Manage Filters Node Topology Filter Create new filter Remove selected filter Filter Name NodeTopology Available Filters Select nodes with 1 neighbors Node gal4RGsig lt 0 0010 Edge null 0 0 Node canonicalName YD NodeTopology that pass the filter Node canonicalN FH BooleanMeta Nnrle nal4R cinzn within distance 1 Apply selected filter The node topology filter allows you to select nodes with at least n neighbors of distance m or less that pass some other selected filter For instance to select all the nodes adjacent to a node with the canonical name matching YD you would select nodes with 1 neighbors
73. rmat has three required features 1 The first line contains two parenthesized assignments for curator and type In the example above the ontology file which is created from the XML GO provides nests all three specific ontologies molecular function biological process cellular component below the ontology named Gene_Ontology type all tells you that all three ontologies are included in that file Following the mandatory title line there are one or more category lines each with the form numberO0 name isa partof numberl number2 isa and partof terms used in GO they describe the relation between parent and child terms in the ontology hierarchy The trailing blank before each left square bracket is not required it is an artifact of the python script that creates these files The Annotation Format By example from the GO biological process annotation file species Saccharomyces cerevisiae type Biological Process curator GO YMRO56C 0006854 YBRO85W 0006854 YJR155W 0006081 and from KEGG species Mycobacterium tuberculosis type Metabolic Pathways curator KEGG RV0761C 10 RV0761C 71 RV0761C 120 58 RV0761C 350 RV0761C 561 RV1862 10 The format has these required features 1 The first line contains three parenthesized assignments for species type and curator In the example just above the annotation file which we create
74. s graphical Destroy View representations of a network and networks the network data not 1 Delete Selected Nodes Edges yet visualized as well as an option for deleting selected nodes and PRETI edges from the current network All deleted nodes and edges can be tete Dated restored to the network via the Edit Restore Deleted Nodes Edges menu item The Edit Menu also supports Preferences editing for properties and plug ins via a Preferences Dialog Preferences editing operates on the cytoscape props file associated with the user s instance of Cytoscape See Command Line Arguments and Properties for more information Data The Data menu allows you to display or hide the network E Select Layout Visualization F management panel CytoPanel 1 It allows you to display or hide Show Hide network tree viewer the attribute browser CytoPanel 2 which lets you view and edit V attribute browser Fs Show Hide advanced window attributes assigned to both nodes and edges See section 7 Node i and Edge Attributes The Data menu allows you to display an advanced window contents of CytoPanel 3 Select Layout Visualization Plugins CytoPane The Select menu contains methods and operations for selecting Ab i 4 nodes and edges and using the current selection to create a new Nodes Edges network and an associated view Select all nodes and edges Ctrl alt A
75. s top right corner CytoPanel 2 Node Attribute Browser Select Attributes Create New Attribute ID ALIASES GO Biological Proce GO Cellular Component Cellular Component YIL133C RPL16A protein biosynthesis cytosolic large ribosomal cytosolic large ribosomal YALOSSW 19 carboxylic acid meta cytosol cytosol YILO6S9C RPS24B oro Copy mall ribosomal cytosolic small ribosomal YPR167C MET16 ar cytoplasm intracellular cytoplasm YGROSSC RPL11B Select All arn ytosolic large ribosomal YLR175W CBF5 Export I Selected Cells small nucleolar ribonucleo YGR254W 1 Entire Table phosphopyruvate hydrata YPR102C RPL11A Show Advanced Window Lay gerousunrar ytosolic large ribosomal Mode Attribute Browser Edge Attribute Browser To swap between displaying node attributes and edge attributes use the bottom tabs Node Attribute Browser and Edge Attribute Browser The attribute browser displays attributes belonging to selected nodes and or edges To populate the browser with rows as pictured above simply select nodes and or edges in a loaded network By default only the ID of nodes and edges is shown To display more than just the ID click the Select Attributes button and choose the attributes that are to be displayed Each attribute chosen will result in one column in the attribute browser in the scr
76. space or tab delimited fields one line per gene with the following format GeneName CommonName ratiol ratio2 ratioN pvall pval2 pvalN Brackets indicate fields that are optional The first two fields are the systematic gene name followed by an optional common name Expression ratios values are provided for each experiment optionally followed by a p value per experiment or other measure of the significance of each ratio value i e whether the ratio represents a true change in expression or whether the value is accurately measuring the presence of a gene according to some statistical model Significance values are generated by a variety of software packages for analyzing expression data generated by DNA microarrays for instance the VERA program from the Institute of Systems Biology nttp www systemsbiology org VERAandsaw A list of other microarray analysis packages is available at nttp www nslij qenetics org microarray soft html Example GENE DESCRIPT gallRG sig gal2RG sig gal3RG sig gallRG sig gal2RG sig gal3RG sig YHRO51W COX6 0 034 0 052 0 152 1 177 0 102 0 857 YHR124W NDT80 0 090 0 000 0 041 0 130 0 341 0 061 21 YKL181W PRST 0 167 0 063 0 230 0 233 0 143 0 089 The first line is a header line giving the names of the experimental conditions Note that each condition is duplicated the first set of columns gives expression ratios and the second set gives significance values The significance
77. starts with the letters SP See the README file for more information ftp ftp ebi ac uk pub databases GO goa HUMAN README Finally run the script to create your three annotation files for human proteins bioproc anno GO biological process annotation e molfunc anno GO molecular function annotation cellcomp anno GO cellular component annotation using the supplied python script It may be necessary to modify this script slightly if RefSeq identifiers are not used as canonical names or if you are using a more recent version of Python python parseAssignmentsToFlatFileFromGoaProject py gene_association goa_human xrefs goa See below for Python script listing 61 Python script examples These scripts described above require Python version 2 2 or later Script 1 parseGoTermsToFlatFile py parseGoTermToFlatFile py translate a GO XML ontology file into a simpler Cytoscape flat file RCS SRevision 1 3 Date 2003 05 18 00 38 43 import re pre sys def flatFilePrint id name isaIDs partofIDs isa if len isaIDs 0 isa isa for isaID in isaIDs isa isaID isa isa partof if len partofIDs gt 0 partof partof for partofID in partofIDs partof partofID partof partof result s s 55 85 id name isa partof result result strip if result isa isa or result partof partof print sys stderr meaning
78. sual style will be applied to your network and you will see a green background and round blue nodes Additionally if you zoom in closer you can see that protein DNA interactions specified with the label pd are drawn with dashed edges whereas protein protein interactions specified with the label pp are drawn with a light yellow color which is difficult to discern on the green background see sample screenshot below The background can be changed through the Visualization menu eoe Cytoscape Desktop Lg d cr 2520 X dao a AATRE Q W G oe galFiltered sif Network Nodes Edges 3310 36200 Nodes 331 0 selected Edges 362 0 selected Welcome to Cytoscape 2 2 Figure Using the Sample Visual Style Protein Protein interactions solid lines are now distinguishable from Protein DNA interactions dashed yellow lines 32 Finally if you select Sample2 gene expression values for each node will be colored along a color gradient between red and green where red represents a low expression ratio and green represents a high expression ratio with thresholds set for the gall RGexp experiment bundled with Cytoscape in the sampleData galExpData pvals file See sample screenshot below eoe Cytoscape Desktop d Edit Data Select Layout Visualization Plugins CytoPanels Help Filters FTF pu 1 eee galFiltered sif Network Nodes Edges 33100 36
79. t covered by this License they are outside its scope The act of running a program using the Library is not restricted and output from such a program is covered only if its contents constitute a work based on the Library independent of the use of the Library in a tool for writing it Whether that is true depends on what the Library does and what the program that uses the Library does 1 You may copy and distribute verbatim copies of the Library s complete source code as you receive it in any medium provided that you conspicuously and appropriately publish on each copy an appropriate copyright notice and disclaimer of warranty keep intact all the notices that refer to this License and to the absence of any warranty and distribute a copy of this License along with the Library You may charge a fee for the physical act of transferring a copy and you may at your option offer warranty protection in exchange for a fee 2 You may modify your copy or copies of the Library or any portion of it thus forming a work based on the Library and copy and distribute such modifications or work under the terms of Section 1 above provided that you also meet all of these conditions a The modified work must itself be a software library b You must cause the files modified to carry prominent notices stating that you changed the files and the date of any change c You must cause the whole of the work to be licensed at no charge to all th
80. ta files will be loaded into Cytoscape For more information about manifest file and how to create it please read the section below Building your own annotation files The annotation server requires that the gene annotations and associated ontology on controlled vocabulary terms follow a simple format This simple format was chosen because it is efficient to parse and easy to use The flat file formats are explained below The Ontology Format By example the Gene Ontology GO curator GO type all 0003673 Gene Ontology 0003674 molecular function partof 0003673 0008435 anticoagulant isa 0003674 0016172 antifreeze isa 0003674 0016173 ice nucleation inhibitor isa 0016172 0016209 antioxidant isa 0003674 0045174 glutathione dehydrogenase ascorbate isa 0009491 0015038 0016209 0016672 0004362 glutathione reductase NADPH isa 0015038 0015933 0016209 0016654 0017019 myosin phosphatase catalyst partof 0017018 57 A second example KEGG pathway ontology curator KEGG type Metabolic Pathways 90001 80001 80003 80002 80004 80005 80006 80007 Metabolism Carbohydrate Metabolism isa 90001 Lipid Metabolism isa 90001 Energy Metabolism isa 90001 Nucleotide Metabolism isa 90001 Amino Acid Metabolism isa 90001 Metabolism of Other Amino Acids isa 90001 Metabolism of Complex Carbohydrates isa 90001 The fo
81. ted and provided that you do these two things a Accompany the combined library with a copy of the same work based on the Library uncombined with any other library facilities This must be distributed under the terms of the Sections above b Give prominent notice with the combined library of the fact that part of it is a work based on the Library and explaining where to find the accompanying uncombined form of the same work 8 You may not copy modify sublicense link with or distribute the Library except as expressly provided under this License Any attempt otherwise to copy modify sublicense link with or distribute the Library is void and will automatically terminate your rights under this License However parties who have received copies or rights from you under this License will not have their licenses terminated so long as such parties remain in full compliance 9 You are not required to accept this License since you have not signed it However nothing else grants you permission to modify or distribute the Library or its derivative works These actions are prohibited by law if you do not accept this License Therefore by modifying or distributing the Library or any work based on the Library you indicate your acceptance of this License to do so and all its terms and conditions for copying distributing or modifying the Library or works based on it 10 Each time you redistribute the Library or any
82. the old formats can be created and used can be found in Appendix B Step 2 Select OBO and Gene Association Files 47 Gene Ontology Wizard cyto cysdirS cytoscape build cytoscape v2 2 annotation gene_ontology obo J Select OBO File The Gene Association files listed below will be loaded cytoscapelbuildicyt 05 cape v2 Z annotation gene_association sad gene association sgd is an annotation file for Saccharomyces cerevisiae lt gt L Add Gene Association File Flip Canonical Name and Common Name Overwrite default species name with Saccharomyces cerevisiae Full list of Gene Association files is available at The Gene Ontology Project Current Annotations Taxonomy table is available from NCBI Taxonomy name id Status Report Page If you choose Gene Ontology in the first step this panel appears to help you select OBO ontology and gene association files This panel has the following functions Select Obo File Button By pressing this button you can choose an OBO file to be loaded Add Gene Association File Button You can add a gene association file to the list by pressing this button Once you select a file the file name will be shown in the list in the left If you click on the file name the species name for the file will be shown You can select multiple gene association files Flip Canonical Name and Common Name Check box The following is an entry in the gene association sgd fi
83. tions and one for pp Protein Protein interactions e Click the pd button and select a blue color e Click the pp button and select a red color e Click the Apply to Graph button You network should now show pd interactions in blue and pp interactions in red Sample screenshot is provided at right 41 Nodes 331 0 selected Edges 362 0 selected Welcome to Cytoscape 2 2 38 Tutorial Visualizing Expression Data on a Network The following tutorial demonstrates how to create a new continuous mapper The goal is to superimpose gene expression data onto a network and to display gene expression values along a color gradient Set Visual Style e Load a sample network From the main menu select File gt Load gt Network and select sampleData galFiltered sif e Loadasample set of expression data From the main menu select File gt Load gt Expression Matrix File and select Node Attributes Edge Attributes Global Defaults Node Label Node Font Node Label Color Node Border Type Node Shape Node Size Node Color Node Border Color Default 4 Change Default Mapping Os sampleData galExpData pvals iorcradieri 3 e Select Visualization gt Set Visual Properties TU Omm mm omm e Select New to create a new Visual Style Name cou mE 3 your new style Sample4 Click the Define button to define the newly Eme jJ c
84. uce you to infringe any patents or other property right claims or to contest validity of any such claims this section has the sole purpose of protecting the integrity of the free software distribution system which is implemented by public license practices Many people have mad generous contributions to the wide range of software distributed through that system in reliance on consistent application of that System it is up to the author donor to decide if he or she is willing to distribute software through any other system and a licensee cannot impose that choice This section is intended to make thoroughly clear what is believed to be a consequence of the rest of this License 12 If the distribution and or use of the Library is restricted in certain countries either by patents or by copyrighted interfaces th original copyright holder who places the Library under this License may add an explicit geographical distribution limitation excluding those countries so that distribution is permitted only in or among countries not thus excluded such case this License incorporates the limitation as if written in the body of this License 13 The Free Software Foundation may publish revised and or new versions of the Lesser General Public License from time to time Such new versions will be similar in spirit to the present version but may differ in detail to address new problems or concerns Each version is given a distin
85. ue is especially significant if the work can be linked without the Library or if the work is itself a library threshold for this to be true is not precisely defined by law If such an object file uses only numerical parameters data structure layouts and accessors and small macros and small inline functions ten lines or less in length then the use of the object file is unrestricted regardless of whether it is legally a derivative work Executables containing this object code plus portions of the Library will still fall under Section 6 Otherwise if the work is a derivative of the Library you may distribute the object code for the work under the terms of Section 6 Any executables containing that work also fall under Section 6 whether or not they are linked directly with the Library itself 6 As an exception to the Sections above you may also combine or link a work that uses the Library with the Library to produce a work containing portions of the Library and distribute that work under terms of your choice provided that the terms permit modification of the work for the customer s own use and reverse engineering for debugging such modifications You must give prominent notice with each copy of the work that the Library is used in it and that the Library and its use are covered by this License You must supply a copy of this License If the work during execution displays copyright notices you must in
86. ultiple nodes or edges are selected all of the normal selection related operations may be performed such as Delete Selected Node Edges Copy To New Network and Invert Selection 54 14 Acknowledgements Cytoscape is built with a number of open source 3 party Java libraries The Cytoscape team gratefully acknowledges the following libraries The Colt Distribution Open Source Libraries for High Performance Scientific and Technical Computing in Java Information is available at http hoschek home cern ch hoschek colt GNU Getopt in Java Information is available at http www urbanophile com arenn hacking download html Graph INterface librarY a k a GINY Information is available at http csbi sourceforge net JDOM Information is available at http www jdom org JUnit Information is available at http junit org JGoodies Looks Information is available at http www jgoodies com freeware looks index html Piccolo Information is available at http www cs umd edu hcil jazz Type Specific Collections Library from Sosnoski Software Solutions Inc Information is available http www sosnoski com opensrc tclib Xerces Java XML parser Information is available at http xml apache org xerces j This product includes software developed by the Apache Software Foundation http www apache org This product includes software developed by the JDOM Project http www jdom org One step Instal
87. ure that your network file uses exact same ID s used in the gene association file Otherwise the annotations will not appear in the Annotation Panel 49 13 Filters The Cytoscape Filter plugin which is packaged with the official Cytoscape 2 2 release and is active by default allows for a wide variety of filtering on node and edge attributes loaded onto Cytoscape networks For example you can easily select all the nodes whose name contains a specific pattern that you define Several types of filters are available Basic filters allow the selection of multiple nodes or edges according to attribute data e String filters allow selection of nodes or edges with attributes matching specified patterns These patterns may include the wildcards and e Numerical filters allow selection of nodes or edges according to numerical attributes and the mathematical operators gt and lt Compound filters allow selection based on the application of pre existing filters e Topology filters allow selection of nodes with neighbors that match some pre existing filter e Boolean filters allow the combination of multiple filters using the AND OR and XOR operators Example filters are shipped with the plugin to get started Using the Plugin If the Filter plugin is loaded then you should see a filter icon on the toolbar If you press the filter icon you will see a filters dialog which looks initially like the following 50 r Manage Filters T
88. us it is not the intent of this section to claim rights or contest your rights to work written entirely by you rather the intent is to exercise the right to control the distribution of derivative or collective works based on the Library In addition mere aggregation of another work not based on the Library with the Library or with a work based on the Library on a volume of a storage or distribution medium does not bring the other work under the scope of this License 3 You may opt to apply the terms of the ordinary GNU General Public License instead of this License to a given copy of the Library To do his you must alter all the notices that refer to this License so hat they refer to the ordinary GNU General Public License version 2 nstead of to this License If a newer version than version 2 of the rdinary GNU General Public License has appeared then you can specify hat version instead if you wish Do not make any other change in kh ph ss Act hese notices Once this change is made in a given copy it is irreversible for that copy so the ordinary GNU General Public License applies to all ubsequent copies and derivative works made from that copy m This option is useful when you wish to copy part of the code of the Library into a program that is not a library 4 You may copy and distribute the Library or a portion or derivative of it under Section 2 in object code or executable form under the
89. work Nodes are placed in hierarchically arranged layers and the ordering of the nodes within each layer is chosen in such a way that minimizes the number of edge crossings yFiles Organic Layout The organic layout algorithm is a kind of spring embedded algorithm that combines elements of the other algorithms to show the clustered structure of a graph Scaling and Rotation Cytoscape provides operations for scaling and or rotating networks or segments of networks The figure at right shows the network view from the organic layout with the selected nodes scaled by a factor of 1 5 and rotated by 90 degrees 29 gt 999 S 19 ce uw s PUN gt 99 02 e A ae gt 3 9 e 2 lt x Se ee eee E NR gt sgy hell 5 m gt e e Te lt 9 oe 39 ous gt e e M E 37 906 rds du B hem N er N amp e 4 9 9 Visual Styles With the Cytoscape Visual Style feature you can easily customize the visual appearance of your network For example you can specify a default color and shape for all nodes use specific line types to indicate different types of interactions or visualize gene expression data using a color gradient All these features are available by selecting Visualization gt Set Visual Properties from the main menu or clicking on the co
90. y done in Cytoscape by specifying the species name on the command line with the s option or by adding a line to the cytoscape props file of the form defaultSpeciesName Saccharomyces cerevisia The automatic canonicalization of names can be turned off with the c command line argument i e Java jar cytoscape jar c or by not loading any annotation This canonicalization of names currently does not apply to expression data Expression data should use the same names as the other data sources or use the canonical names as defined by the synonym table 6 Loading Gene Expression Data Interaction networks are useful as stand alone models However they are most powerful for answering scientific questions when integrated with additional biological information such as gene or protein expression levels Once loaded expression ratios levels may be visually superimposed on the network used in a filter to select a subset of nodes or used to identify active modules and subsystems via plugin analysis tools An expression data set can be loaded at any time but are only relevant once a network has been loaded FORMAT Gene expression ratios or values are specified over one or more experiments using a text file Ratios result from a comparison of two expression measurements experiment vs control Some expression platforms such as Affymetrix directly measure expression values without a comparison The file consists of a header and a number of
91. ytoscape Editor To add a node to a network drag and drop a shape from the palette onto the canvas To connect two nodes with an edge drag and drop the arrow onto a node on the canvas then move the cursor over a second node and click the mouse Directed Edge Add a Node CytoPanel 2 a Node Attribute Browser Select Attributes Create New Attribute Node Attribute Browser Edge Attribute Browser Welcome to Cytoscape 2 2 To add a node to a network drag and drop a node shape from the palette onto the canvas To connect two nodes with an edge drag and drop an arrow shape onto a node on the canvas This node becomes the source node of the edge Move the cursor and a rubber banded line follows the cursor As the cursor passes over another node that node is highlighted and the 41 rubber banded line will snap to a connection point on that second node Click the mouse while over this node and the connection is established You can abort the drawing of the edge by clicking on an empty spot on the palette Note that if you change the Visual Style the palette used by the current network view will also change to be consistent with the mappings in the new Visual Style There is also an Edit gt Connect Selected Nodes menu item that when chosen creates a clique amongst the selected nodes The editor provides accelerators for adding nodes an

Cytoscape Manual

Contents

Download Pdf Manuals

Related Search

Related Contents