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Cytoscape 2.3.2 User Manual

1. Mosis Attribute Eyar ws oon Edge Aria Brescia htk Anpribupre Berreci Welceeng to Conca 2 3 Left ci um o i Z00M kidek a dra bo RAN Figure Using the default Visual Style You can flip through different visual styles by making a selection from the Visual Style pull down menu available directly to the right of the color wheel 36 Cytoscape 2 3 2 User Manual For example if you select Samplel a new visual style will be applied to your network and you will see a white 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 red edges whereas protein protein interactions specified with the label pp are drawn with a light blue color see sample screenshot below eh A Cyroscape Deinrop New Setia File Edi Whew Select Layout Plugin Help d te t us 0 wc Sample Sme 8 3d gall send sif hes Dpes ASGUM 33100 3620 Mose Asbribute Bemeser n S oO Kr iu Ae rere ts Edge Ambre Grewia Aer Arribi Binet Welceeng t5 Cytodcape 2 3 Left chrk drag te ZOOM Madtieotick a drag bo PAM Figure Using the Samplel1 Visual Style Protein Protein interactions solid blue lines are now distinguishable from Protein DNA interactions dashed red lines Finally if you select Sample2 gene expression values for each node will be colored along a color gradient betwee
2. 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 Node and Edge Attributes Cytoscape allows the user to add arbitrary node and edge information to Cytoscape as node and edge attributes At tributes 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 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 YALO01C metabolism YARO02W apoptosis YBL007C 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 will
3. The ability to save a session You can now save all of your work in Cytoscape to a single file When re opened this file will return Cytoscape to the state in which you left it including all networks attributes and properties A node grouping plugin This will allow one node to contain and display subnetworks Enhanced Undo Redo support An enhanced attribute browser An enhanced Ontology Server Wizard An improved command line interface The ability to rename networks The GraphMerge cgi bin moin cgi GraphMerge plugin included by default Enhanced context or pop up menus for nodes e Many performance improvements and bug fixes e A rewritten bird s eye view of the network that is enabled by default e The ability to load expression data according to node attribute such as a commercial probeset identifier instead of ndoe ID Are you an experienced Cytoscape user If so you should definitely read the following sections because important parts of Cytoscape have changed and what used to work may no longer work as you expect Properties cytoscape props and vizmap props handling properties Rendering Engine renderer e Command line arguments Zcommand line args e The menu system menus Cytoscape 2 3 2 User Manual Network Panel Navigation navigation Launching Cytoscape Cytoscape is a Java application that runs on Linux Windows and Mac OS X System requirements The system
4. def flatFilePrint id name isalDs partofIDs isa if len isaIDs gt 0 isa isa for isaID in isaIDs isa isaID isa isa t 1 partof if len partofIDs gt 0 partof partof for partofID in partofIDs partof partofID partof partof t result np np s np np s np np s np np s np np id name isa partof result result strip if result isa isa or result partof partof print gt gt sys stderr meaningless term np np s np np result else print result if len sys argv 2 print usage np np s lt someFile xml gt np np sys argv 0 sys exit inputFilename sys argv 1 print gt gt sys stderr reading np np s np np inputFilename text open inputFilename read print gt gt sys stderr read np np d characters np np len text regex go term gt lt go term gt cregex pre compile regex re DOTALL matches newlines m 7 pre findall cregex text print gt gt sys stderr number of go terms np np d np np len m regex2 lt go accession gt G0 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 geneontolog
5. Cytoscape 2 3 2 User Manual Table of Contents C ytoscape 2 3 2 User DISTRETTO EO 2 Introd HO E EE E idet em A RP E EM Eis PEDI MEDIIS MM DEUM PIN 2 Laune nno v OS CS casses p testi emte td pbi bung E e EE 4 Ouck Touro C Vu m c 5 Te VIS a e cate ep EEE ee ns aie E S E E E E E E E E 7 Nennok Mime m BE e E U URINAM M S Db PI E 10 The Network Overview WindOW sccccc2scsnncsiadsacesuecansancadsadestacertoduscandeaecistaecatandes Ee i ubbace id d oer i 1 Command Line Arceuments amd Properties escicicarcisnctaniacc nage EEEE EAE E ENEE 12 Command Line ATEUFRICBES sof apne de dembieum es ptit dase oc EEE EE eE nE E 12 VLOSOde Prope Ei ouiosucebeoues roD quEDIUEM E UII I PH DIDI DU EH AUN S NOU USE 14 Building and Storing Interaction Networks ccc cece cence nee iite ein nen EEE EERE se e esse eese essere neas 15 Loading Gene Expression Attribute Matrix Data w ccgeisciveersss ianveislaaenscseredviecscesviceenanetidlasancepenedelacimenviedan 18 Node and Edge AMIDUIES stsscoscatenesaccurenaanccenasanetiecoustana ini arae e endete vex Men ced Sa tend Son MUR RPM 21 varus nre rB and Layou RETE E E 24 K O A E N E E a E RPT PE UE 24 Automate Layout A lCOnmtninS tsc1s 1cccenerscimeaedcuceawsecuiensedaremuncanseeidsenaaehea whan AEAEE EES 24 Aun TP OU setter ces tect E JP 28 BAUER gt E E A E E m mA 35 Introdguetion 1o Visual SIVICS serieren rekri ad PEE a aa a a E at 3
6. The centers of selected nodes are aligned along a line 7 defined by the midpoint between the left and right most nodes 33 Cytoscape 2 3 2 User Manual Horizontal Align Right The right hand sides of the selected nodes are aligned with the right most node Starting position for all vertically distributed examples 77 unn simam n sum Table 9 Vertical Distribute Top The tops of the selected nodes are distributed evenly between the top most and bottom most nodes which should stay stationary me Vertical Distribute Center The centers of the selected nodes are distributed evenly between the top most and bottom most nodes which should stay station ary Vertical Distribute Bottom The bottoms of the selected nodes are distributed evenly between the top most and bottom most nodes which should stay station ary Starting position for all horizontally distributed examples l E LI lem 34 Cytoscape 2 3 2 User Manual Horizontal Distribute Left The left hand sides of the selected nodes are distrib uted evenly between the left most and rigth most nodes which should stay sta tionary Horizontal Distribute Center The centers of the selected nodes are distributed evenly between the left most and rigth most nodes which should stay stationary Horizontal Distribute Right The right hand sides of the selected nodes are dis tributed evenly
7. 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 z If you press the filter icon you will see a filters dialog which looks initially like the following Manage Hikers There is no filter currently selected To edit a filter select it From the Available filters list if Create new filter the list is empty you can create a new filter wath the Create new filter button Available Filters Node nulls Edge nullm T0 If the first filter is selected then the dialog looks as shown n Manage Filters Numeric Attribute Filter Create mew filter Remove selected filter acco Wissel Mince allot Available Filters Select graph objects of type Node n Node nullsc 0 with a value for numeric attribute m thatis FJ 0 0 Edge nullad 0 Apply selecred 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 current
8. SGD http db yeastgenome org cgi bin locus pl locus 1D places the SGD link under the yeast submenu This link will appear in Cytoscape as Biological resources Bio GRID Web resources UniProt fly wn rtm hum an Mouse In a similar fashion one can added new submenus The ID string in the URL 1s a place holder for the node label When the popup menu is generated this marker is substituted with the node label In the above example the generated SGD link for YIM protein is http db yeastgen ome org cgi bin locus pl locus YIM1 Currently there is no mechanism to check whether the constructed URL query is correct and if the node label is meaningful Similarly there is no ID mapping between various identifiers For example a link to NCBI Entrez from a network that uses ensembl gene identifiers as node label will produce a link to Entrez using ensembl ID which results 56 Cytoscape 2 3 2 User Manual in an incorrect link It is the users responsibility to ensure that the node label that is used as the search term in the URL link will result in a meaningful link Adding or Removing links The default links are defined in a linkout props file contained in the linkout jar These links are normal java properties and can be editited while running in the Edit amp 8594 Preferences menu New links can be defined this way as well New links can be defined at startup in a separate file and loaded from the command line eithe
9. 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 cgi bin moin cgi RefSeq number These two naming systems IPI and RefSeq cgi bin moin cgi RefSeq are two of many that you can use for canonical 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 Decide which naming system you want to use 2 Download ftp ftp ebi ac uk pub databases GO goa HHUM AN xrefs goa This cross reference file when used stra tegically allows you to create Cytoscape compatible annotation files in which the canonical name is the one most meaningful to you 3 Examine xrefs goa to figure out which column contains the names you wish to use 4 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 000
10. rma weenzian dU dare 1106 2005 16 57 ftaved by midari auta genernedeby DAC Edi 1 419 ree 3 delau namezpace gene amiatoge remark ces version EReisionc 111 rubreldef gorlen yetgi enit CO phen zubzeidef gnzlim goa CO and proteome slim Pubie gorlan plara Pla GO flim zubzerder gorlem generic Generic CO slim zubzeidef gorubset_prok Prokaryatic GO subset ms If you choose Gene Ontology in the first step this panel appears to help you first select an OBO ontology file The wizard displays the header information of the OBO file loaded Once an OBO file is loaded the Next button becomes enabled Click the Next button to proceed Step 3 Select Gene Association File Gene Ontology Wizard Select Annotation Files iene Asiaciatien Files Add i Trarster GO Species Nase To Neder Preview of Gene Avveciation File Header Pres ies Node Ds and Species TEROGAM Seccharce a YOR374W Sacchared 1 TILOSOW Saccharom THLI6GOW Saccharor YDR247W Saccharon YR AW acenaron YML ASC Satcharom TELLS facchanan TELIGTC Sicrcharom YOLTIOIC Saccharor Wersion Revizipn 1 1175 ipare Oh MO s2005 Fro Saccharomyces Cenome Darabaze SCD WEL Biip fare ai genome org icentaect Email yepp gurore er genome arg Funding NH RI at US NIH gram number 5 P41 HODDI315 i al EE m Tr 6 Symbol GOAspect GO Synomym GO Taxon ID GO Term VRRLS2 Saccharon YAR SSW Sa
11. you can click the GO button 3 in the Attribute Browser panel or on the File Import On tology Ontology Mapper menu and the Ontology Mapper dialog will open 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 sure that your network file uses exact same ID s used in the gene association file Symbol or Synonym column Otherwise the annotations will not appear in the Annotation Panel 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 Numerical filters allow selection of nodes or edges according to numerical attributes and the mathematical operators gt and lt 52 Cytoscape 2 3 2 User Manual Compound filters allow selection based on the application of pre existing filters Topology filters allow selection of nodes with neighbors that match some pre existing filter
12. 1 i a 8 dio E i m m j XN 1 i i Sra m p p T i ee p ED i k re Yo FA F P o fat enhn LL F E i Ths PF y 3 rd p r 20 ir A E Fs Fr 5 Fj ir i g Ji Align Distribute TEE Pl ho X d Diwiriberia EXE The Layout Align Distribute menu opens the Align Distribute dialog The Align buttons of the dialog provides different options for either vertically or horizontally aligning selected nodes against a line The differences are in what part of the node gets aligned e g the center of the node the top of the node the left side of the node The Distribute buttons evenly distribute selected nodes between the two most distant nodes along either the vertical or horizontal axis The differences are again a function what part of the node is used as a reference point for the distribution The table below provides a mapping from button to name to result Starting position for all aligned examples 3l Cytoscape 2 3 2 User Manual 32 Cytoscape 2 3 2 User Manual Table 8 Vertical Align Center The centers of selected nodes are aligned along a line defined by the midpoint between the top and bottom most nodes Wo Vertical Align Bottom The bottoms of the nodes are aligned with the bottom most node Horizontal Align Left The left hand sides of the selected nodes are aligned with the left most node a Horizontal Align Center
13. Cytoscape 2 3 Some of the layout algorithms provided with Cytoscape 2 3 are Cytoscape Spring embedded Layout 24 Cytoscape 2 3 2 User Manual 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 This algorithm is available from the Layout Cytoscape Layouts Spring Embedded menu item A sample screen shot is provided below 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 This algorithm is available from the Layout yFiles Circular menu item 25 Cytoscape 2 3 2 User Manual Ps fa eee E lt v de e victa Y ii T uz duni Ew 1 yFilesHierarch ical Layout The hierarchical layout algorithm is good for representing main direction or flow within a network Nodes are placed in hierarchically arranged layers and the ordering of the nodes within each la
14. MERCHANTABILITY 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 ASSUME THE COST OF ALL NECESSARY SERVICING REPAIR OR CORRECTION 16 IN NO EVENT UNLESS REQUIRED BY APPLICABLE LAW OR AGREED TO IN WRITING WILL ANY COPYRIGHT HOLDER OR ANY OTHER PARTY WHO MAY MODIFY AND OR REDISTRIBUTETHE LIBRARY AS PERMITTED ABOVE BE LIABLE TO YOU FOR DAMAGES INCLUDING ANY GENERAL SPECIAL INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OR INABILITY TO USE THE 69 Cytoscape 2 3 2 User Manual LIBRARY 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 EVEN IF SUCH HOLDER OR OTHER PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES END OF TERMS AND CONDITIONS 70
15. Server Wizard is a 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 Step 1 Select Data Format e Gime Ontology Wiza Welcome to Gene Ontology Wizard Which file formar do you want to load Yoldagi BieDaraserver animo and oem Gene Oemolegy obo and gene arzocirnion Cytoscape supports the Following file formats Cytoscape BioDaraserver Forrmar e Onte syno and anne files is Manifest file required a CO Annotation and Ontology Format OEO and Gene Association files Latest data is available at Open Biomedical Ontologies Taxonomy table is obtained from NCBI In this panel you can select two types of data formats Cytoscape BioDataServer cgi bin moin cgi 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 cgi bin moin cgi BioDataServer A description of how the old formats can be created and used can be found in Appendix B Step 2 Select OBO File 50 Cytoscape 2 3 2 User Manual Gene Ontology Wizard Select Ontology File Please select an ontology data file in GEZ format DEC Fik fhame mez5krcyioscape restDaraannpiateonfgene ontbplpgy abn Header Preview l
16. 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 encourage naming genes and 17 Cytoscape 2 3 2 User Manual 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 chromo some identifier and one or more common names that are used by ordinary res
17. arguments have changed in version 2 3 so please read this section carefully Cytoscape recognizes a number of optional command line arguments including run time specification of network files attribute files and session files This is the output generated when the cytoscape is executed with the h or help flag usage java Xmx512M jar cytoscape jar OPTIONS h help Print this message V version Print the version number S Session lt file gt Load a cytoscape session cys file N network file Load a network file any format e edge attrs file Load an edge attributes file edge attribute format n node attrs lt file gt Load a node attributes file node attribute format m matrix file Load a node attribute matrix file table p plugin file Load a plugin jar file directory of jar files plugin class name or plugin jar URL P props file Load cytoscape properties file Java properties format or individual property P name value V vizmap file Load vizmap properties file Java properties format Any file specified for an option may be specified as either a path or as a URL For example you can specify a network as a file assuming that myNet sif exists in the curret working directory cytoscape sh N myNet sif Or you can specify a network as a URL cytoscape sh N http example com myNet sif 12 Cytoscape 2 3 2 User Manual Table 5 h help This
18. canonicain H Ecole ner gt Mala leche i 1 Apply selected filter Thenodetopology 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 neighbors within distance 1 that pass the filter Node canonicalName YD Boolean Filter Manage Filters Benen hysa Fij Create mi Filter eres tebected finer Filter Hame Booleankleza wailable Filer Select ghjects that pais va of the velected filters TOME 7 Node gaMRGHg lt 0 0010 Mode ARGHA cures doe mulso doe fuls 0 Hoge gt tanga igre FDA Mode canonaalame YUL MO Topai Node Topot Besini tao gt jisit ure Li Ursie meU ee Mode ga RGHga 0 0 Apply selected Aher Megane TheBooleanMeta 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
19. 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 third 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 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 ap
20. 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 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 Connect Selected Nodes menu item that when chosen creates a clique amongst the selected nodes The editor provides accelerators for adding nodes and 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 cgi bin moin cgi 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 a
21. gt 0 and len np gt 0 result ipi np return result if len sys argv 3 print error parse gene associations file from GO goa xrefs file gt sys exit associationFilename sys argv 1 xrefsFilename sys argv 2 Species Homo sapiens ipiToNPHash readGoaXrefFile xrefsFilename tester IPI00099416 print hash size np np d np np len ipiToNPHash print test map np np s gt NP 054861 np np s np np tester ipiToNPHash tester bioproc open bioproc txt w molfunc open molfunc txt w cellcomp open cellcomp txt w bioproc write species np np s type Biological Process curator GO n np np species molfunc write species np np s type Molecular Function curator GO n np np species cellcomp write species np np s type Cellular Component curator GO Wn np np species lines open associationFilename read split Mn sys stderr write found np np d lines M np np len lines for line in lines if line find 0 or len line 2 continue tokens line split t goOntology tokens 8 golDraw 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
22. in the Properties section of the dialog These properties are configurable via Add Modify and Delete operations Cytoscape Preferences Editor OA T Properties Property Mame bioDataServer PleazeSpecify canonicalizeMames True defaultSpeciesName Saccharomyces cerevisiae defaultVisualstyle default Plugins Plugin Location fcellarfusers mes cytoscape build cytoscape v2 3 plugins Automatic a fcellarfusers mes cytoscape build cytoscape v2 5 plugins CraphMer fcellarfusers mes cytoscape build cytoscape w2 3 plugins ManualLay fcellarfusers mes cytoscape bulld cytoscape v2 3 plugins browser jar E Local Add NOTE Changes to these properties and plugins are used in the current session ONLY unless otherwize specified below Default Visual Styles Only check this option if you want the current visual styles to be defaults in ALL future cytoscape sessions Your current visual styles are automatically saved in your Cytoscape session file and won t be lost Make Current Visual Styles Default Default Cytoscape Properties Only check this option if you want the current Cytoscape properties to be defaults in ALL future cytoscape sessions Your current Cytoscape properties are automatically saved in your Cytoscape session file and won t be lost Make Current Cytoscape Properties Default Ok Cancel Some common properties are described below 14 Cytoscape 2 3 2 User Manual Table 7 Property name Default value Va
23. 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 Strings 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 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 af
24. network and to display gene expression values along a color gradient e Load a sample network From the main menu select File Import Network and select sampleData galFiltered sif Load a sample set of expression data From the main menu select File Import Attribute Matrix and select sampleData galExpData pvals 42 Cytoscape 2 3 2 User Manual Click the color wheel z button on the tool bar e Select New to create a new Visual Style Name your new style Sample4 Click the Define button to define the newly created Visual Style In the Set Visual Properties Dialog box select Node Attributes Node Color Click the New button in the mapping panel 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 to the section above Select continuous mapper and enter a descriptive name For example enter Color Gradient From the Map Attribute pull down menu select gall RGexp Click the Add Point button twice to add two data points e Set the first point to 1 Below Yellow Equal White e Set the second point to 2 Equal Red Above Black Click the Apply to Network button This visual mapper will set all nodes with a gal I RGexp value less than 1 to Yellow and all nodes with a gall RGExp value greater than 2 to Black Additionally all valu
25. np np s np np s has go term np np s np np tester printName goID if goOntology C cellcomp write np np s np np s n np np printName goID elif goOntology P bioproc write np np s np np s n np np printName goID elif goOntology F molfunc write np np s np np s n np np printName goID Appendix B GNU Lesser General Public License GNU LESSER GENERAL PUBLIC LICENSE Version 2 1 February 1999 Copyright C 1991 1999 Free Software Foundation 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 64 Cytoscape 2 3 2 User Manual 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 software 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
26. 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 7792 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 G0 0000001 name mitochondrion inheritance namespace biological process def The distribution of mitochondrial including the mitochondrial genome into daughter cells after mitosis or meiosis mediated by interactions between mitochondria and the cytoskeleton PMID 10873824 PMID 1 is a 60 0048308 organelle inheritance is a 60 0048311 mitochondrion distribution Term id G0 0000002 name mitochondrial genome maintenance namespace biological process def The maintenance of the structure and integrity of the mitochondrial genome G0 ai is a GO 0007005 mitochondrion organization and biogenesis 49 Cytoscape 2 3 2 User Manual gene association sgd annotation file for yeast SGD 5000003916 AAD10 G0 0006081 SGD_REF 000042151 PMID 10572264 ISS P aryl alcohol dehydrogenase putative YJR155W gene taxon 4932 20020902 SGD SGD 000005275 AAD14 G0 0008372 SGD_REF S000069584 ND e aryl alcohol dehydrogenase putative YNL331C gene taxon 4932 20010119 SGD Gene Ontology Server Wizard The Gene Ontology
27. of each CytoPanel cgi bin moin cgi CytoPanel The icon and tooltip will change based on the CytoPanel cgi bin moin cgi CytoPanel state If the CytoPanel cgi bin moin cgi CytoPanel is docked clicking on the icon will float the CytoPanel cgi bin moin cgi CytoPanel as indicated by the Float Window tooltip Alternatively if the CytoPanel cgi bin moin cgi CytoPanel is floating clicking on the icon will dock the CytoPanel cgi bin moin cgi CytoPanel as indicated by the Dock Window tooltip zal r4 Float Dock Window Window Rendering Engine In Cytoscape 2 3 a new network rendering engine is being introduced The goal of the rendering engine is to be able to display large networks gt 10 000 nodes yet retain interactive speed To accomplish this goal a technique involving level of detail is being used Based on the count of objects nodes and edges being rendered an appropriate level of detail is chosen For example by default node labels if present are only rendered when less than 100 nodes are visible because drawing text is a relatively expensive operation This can create some unusual behavior If the screen currently contains 98 nodes node labels will be displayed If you pan the screen such that now 101 nodes are displayed the node labels will disappear As another example if the sum of rendered edges and rendered nodes is greater than or equal to a default value of 2000 a very coarse level of detail is chosen
28. 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 annota tions shtml The rightmost column contains links to tab delimited files of gene associations by species Choose the species you 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 G0 0003677 PUBMED 9714827 TAS F Deoxyribonuclease II precursor IPI00010348 protein taxon 9606 SPTR SPTR 000115 DRN2 HUMAN G0 0004519 GOA spkw IEA F Deoxyribonuclease II precursor IPI00010348 protein taxon 9606 20020425 SPTR SPTR 000115 DRN2 HUMAN G0 0004531 PUBMED 9714827 TAS F 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 G0 IPI00010348 0003677 IPI00010348 0004519 IPI00010348 0004531 or species Homo sapiens type Biological Process curator G0 NP_001366 0006259 NP_001366 0006915 NP_005289 0007186 61 Cytoscape 2 3 2 User Manual NP_647593 0006899 The first sample contains molecular function annotation for proteins
29. the layout 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 XGMML FORMAT XGMML is the XML evolution of GML and is based on the GML definition The XGMML file format specification is available at http www cs rpi edu puninj XGMMI XGMML is now preferred to GML because it offers the flexibility associated with all XML document types If you re unsure about which to use choose XGMML 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 N option works for SIF GML and XGMML FOR EXAMPLE To load a sample molecular interaction network in SIF format use the menu File gt Import 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 Import 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 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
30. 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 cond2 condl cond2 NumSigConds text text condl cond2 tab tab RATIOS tab tab 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 cgi bin moin cgi 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 The second format is similar to the first except that the duplicate column names are omitted and there is no NumSigConds cgi bin moin cgi NumSigConds fields This format specifies data with ratios but no significance values 20 Cytoscape 2 3 2 User Manual 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 of tabs equ
31. where edges are always straight lines nodes are always rectangles and no antialiasing is done The default values used to determine these thresholds can be changed by setting properties in the Edit Preferences menu Beware The greater these thresholds become the slower per formance will become If you work with small networks a few hundred nodes this shouldn t be a problem but for large networks it will produce noticeable slowing The various thresholds are described below Table 14 render coarseDetail If the sum of rendered nodes and rendered edges equals to or exceeds this number a Threshold very coarse level of detail will be chosen and all other detail parameters will be ignored this value defaults to 2000 render nodeBorderThreshold If the number of rendered nodes equals to or exceeds this number node borders will not be rendered this value defaults to 200 render nodeLabelThreshold If the number of rendered nodes equals to or exceeds this number node labels will not be rendered this value defaults to 100 render edgeArrow Threshold If the number of rendered edges equals to or exceeds this number edge arrows will not be rendered this value defaults to 300 render edgeLabelThreshold If the number of rendered edges equals to or exceeds this number edge labels will not be rendered this value defaults to 150 When printing networks or exporting to formats such as PostScript cgi bin moin cgi PostScript the highes
32. 115 IPI00010348 ENSP00000222219 NP 001366 BAA28623 AAC77366 AAC35751 AAC39852 BAB55598 AAB51172 AAH10419 2960 DNASE2 1777 DNASE2 SP 000116 IPI00010349 ENSP00000324567 ENSP00000264167 NP_003650 CAA70591 327 AGPS 8540 AGPS SP 000124 IPI00010353 ENSP00000265616 ENSP00000322580 NP 005662 BAA18958 BAA18959 AAH20694 7993 D852298E Note that line wrapping has occurred here each line in this example 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 cgi bin moin cgi 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 Python script examples These scripts described above require Python version 2 2 or later Script 1 parseGoTermsToFlatFile py 62 Cytoscape 2 3 2 User Manual parseGoTermToFlatFile py translate a GO XML ontology file into a simpler Cytoscape flat file RCS Revision 7792 Date 2006 07 19 16 28 06 0700 Wed 19 Jul 2006
33. 2 User Manual Click the New button and enter a name for your new visual style when prompted Then click the Define button You will now see the main Visual Styles Properties dialog box shown below 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 For example to set the default node shape to triangles select Node Attributes Node Shape Then click the Change Default button and select the Triangle icon from the selection list e VizMapper Default Change Default C New Duplicate Rename Delete Apply to Network Close To apply your visual style to your network hit the Apply to Network button available in the bottom of the dialog panel Tutorial 2 Creating a New Visual Style with a Discrete Mapper The following tutorial demonstrates how to create a new visual style with a discrete mapper The goal is to draw Protein DNA interactions with blue edges and Protein Protein interactions with red edges e Load a sample network From the main menu select File Import Network and select sampleData galFiltered sif Click the color wheel button on the tool bar e Select New to create a new Visual Style Name your new style Sample3 Click the Define button to define the newly created Visual Style In the Set
34. 3 2 User Manual 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 LICENSE TERMS AND CONDITIONS FOR COPYING DISTRIBUTION AND MODIFICATION 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 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 with
35. 6 Visual Attributes Graph Attributes and Visual Mappers ccccececcececeec eee ee eee eeeneeeeeeneeeenseeeeaeneegs 38 Misudl Oy e TOMAS A E E RERO RN NRI NNNM E EE E ienceaenass 40 Au EEUU Wau al Sy IS ME IE oO Oo ESS 44 POT NEO E eoe RE EEE sacedcoran 2ecangeavaieucnadetene deut aspe UU CDM du hop ERE 45 re E ACIS MR To mmm 46 PRG IO JE THO pc Se cece teers apse EEA E E E catt ano atas que daw Rep E eut eO dene ds Rae e 48 POLEN NE OO DOO LU m 48 Gene Ontolob e Server MUIZIEO auccdioeeecuese derbi etd subiendo pda tubom etate ptis EE Eer EE 50 eI S RE TE OO tm E E E E 22 IBS PU 56 ZXSKIONICOOCEIIE BS eor ecosmer n vint en cece enue NER Dese eEUPSR ORI SU ITA OMA LANI IE REM EPI EPI OR as RM PRU DI 57 Appendix A Old Annotation Server Format esssssssessesessessssessesee sense eese esses esse ee essere re eene 57 Gene Ontology Server WIZOEQ nsicescorricscensassereavsss edu vio EE EAE NET E EEE 57 Building your own annotation files 2 2 cece cece cece nee ee nee nee ence ne me e me ee EE EEE EG EEE EERE EEE eese essere nas 59 I cad Data TBto tOSCdDE oocserecowepuctue deu tense sinn es upEMPte serene tun etenctteeaeece ean serera oa atenesecarnceacnennieves 60 Get ne and Rerormattte GO Dade ses haee cus tb Er Edu THERME U vbt ao phus uibaE e uio ed qu uino dee Pda td 61 Appendix B GNU Lesser General Public License e neceteriei Se muti e epo Upo base iu
36. N gallRG gal4RG gal80R gallRG gal4RG gal80R YHROSIW COX6 0 034 0 111 0 304 3 75720e 01 1 56240e 02 7 91340e 06 YHR124W NDT80 0 090 0 007 0 348 2 71460e 01 9 64330e 01 3 44760e 01 YKL181W PRS1 0 167 0 233 0 112 6 27120e 03 7 89400e 04 1 44060e 01 Of 2a After loading the network load the node attribute file sampleData gal probeset na using the menu options File Import Node attributes This file is shown in part below Probeset YHRO51W probeset2 YHR124W probeset3 YKL181W probeset4 2b After loading the node attribute file select the expression data file sampleData galExpPvals probeset pvals shown in part below GENE COMMON gallRG gal4RG gal80R gallRG gal4RG gal80R probeset2 COX6 0 034 0 111 0 304 3 75720e 01 1 56240e 02 7 91340e 06 probeset3 NDT80 0 090 0 007 0 348 2 71460e 01 9 64330e 01 3 44760e 01 probeset4 PRS1 0 167 0 233 0 112 6 27120e 03 7 89400e 04 1 44060e 01 After selecting this file in the field labeled Assign values to nodes using select Probeset You will see that this loads exactly the same expression data as in Case 1 but provides extra flexibility in case the node name cannot be used as an identifier 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 line or contains all the measurements for a particular gene No name conversion is applied
37. Preferences View The View menu allows you to display or hide the network management panel CytoPanel cgi bin moin cgi CytoPanel 1 the attribute browser CytoPanel cgi bin moin cgi CytoPanel 2 the Network Overview in CytoPanel cgi bin moin cgi CytoPanel 1 and the Advanced window The View menu also allows you to open the VizMapper cgi bin moin cgi VizMapper and lock the VizMapper cgi bin moin cgi VizMapper The View Desktop provide futher control over the various CytoPanels cgi bin moin cgi CytoPanels Cytoscape 2 3 2 User Manual Wey Select Layout Plugins Help Shows Hide advanced window w Shows Hide attribute browser FS vw Shows Hide network tree viewer wf Shows Hide Hetwork Overview c Open VizMapper Lock VizMapper Desktop Select The Select menu contains different options selecting nodes and edges It also contains the Select Use Filters option which allows filters to be created which can be used to automatically select portions of a network whose node or edge attributes meet a filtering criterion Layout Plugins Help Mouse Drag Selects Modes Edges Select all nodes and edges Ctri Alt A Deselect All Nodes and Edges Ctri Altt Shitt A WE Use Filters F7 Layout The Layout menu has an array of features for organizing the network visually The top of the menu contains tools for manipulating sections of networks These tools include scale rotate distribute and align The bo
38. Visual Properties Dialog box select Edge Attributes Edge Color Click the New button in the mapping panel 41 Cytoscape 2 3 2 User Manual 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 to the text above Select discrete mapper and enter a descriptive name For example enter Interaction_Type_Color e From the Map Attribute pull down menu select interaction You should now see two buttons one for pd Protein DNA interactions and one for pp Protein Protein interactions e Click the pd button and select a blue color Click the pp button and select a red color Click the Apply to Network button You network should now show pd interactions in blue and pp interactions in red Sample screenshot is below eee Cytoscape Deisrop New Session File Ed Vips Select Layout Plugins Help d 259 X Gow ae CytesPate 1 Mes Lies l umh 1 Medos Gigen BEENNEEND 50 eao E y o im aL dH T lFr tl V v uS sof Edge Armribute Breverer Muryenrk Arribi Fraze Welceenr to Cytoscape 2 3 Left chck drag te ZON Matie tick a drag bo PAM Tutorial 3 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
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40. acterium tuberculosis type Metabolic Pathways curator KEGG RV0761C 10 RV0761C 71 RV0761C 120 RVO761C 350 RVO761C 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 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 1 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
41. al to the number of conditions followed by the LAMBDAS 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 GML or XGMM L files Tradi tionally 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 ex pected 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. ation is available at http java freehep org 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 Installation of the Cytoscape software is accomplished using the InstallAnywhere cgi bin moin cgi InstallAnywhere product from ZeroG Software Inc http zerog com 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 57 Cytoscape 2 3 2 User Manual Step 1 Select Data Format Gene Ontology Wizard Welcome to the Gene Ontology Wizard Which Fils Fonmat do you went Ep load CO Gene Onbology obo and gene association Hote Please put all date files both annotation and ontology inthe came directory Otherwise the Gene Ontology Wizard Press the Text button bo continue m aa cen a If you want to use the old manifest file to load annotations select Cytoscape BioDataServer cgi bin moin cgi BioDataServer Step 2 Specify Manifest File Gene Ontology Wizard Manifest file should include both annotation and ontology file
43. ations 67 Cytoscape 2 3 2 User Manual 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 include 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 ins
44. beas trabe aou E E etia bee Pub evbr pio tute 64 Cytoscape 2 3 2 User Manual Cytoscape 2 3 2 User Manual This document is licensed under the Creative Commons license http creativecommons org licenses by 2 5 2006 Authors The Cytoscape Collaboration The Cytoscape project is an ongoing collaboration between Table 1 University of California at San Diego Institute for Systems Biology Memorial Sloan Kettering Cancer Center a BETTERIN G v C e Be ae E z T D T e gt E 4BLISHED Institut Pasteur Agilent Technologies Nghe i Agilent Technologies 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 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 interactions 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 vis
45. between the left most and rigth most nodes which should stay stationary 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 along a color gradient 35 Cytoscape 2 3 2 User Manual All these features are available by selecting the View Open Viz Mapper menu item or clicking on the color wheel mS button on the main button bar Introduction to Visual Styles The Cytoscape distribution includes several predefined visual styles to get you started To demonstrate these styles try out the following example e Load a sample network From the main menu select File Import Network and select sampleData galFiltered sif e Layout the network select Layout yFiles Organic Load a sample set of expression data From the main menu select File Import Attribute Matrix 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 ee Cytescape Deskrop New HHT Fia Edi Wiew Select Layout Plugins Help iod FA LOX Gem m a Editor Medes D peb EE oie ooo Bon galFitened sif
46. brary 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 68 Cytoscape 2 3 2 User Manual 10 Each time you redistribute the Library or any 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 respons ible for enforcing compliance by third parties with this License 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 1s h
47. ccharon YHEZZUM aorharor YiLOS OW Saccharam YDLOAQI Sacchnom TALODIW Sacchargee 1955 RHMA 155 RRMA 155 RRMA 215 RRMA 215 RRMA 215 RRMA COGAIS CO E A oale Pae GOODS at COooos7ss COooes73s Waolecular F lia agical P liahagical P Cellular Ca Mabecular F Mabecular F 15t rFMA 155 r amp EHA 155 rE NAI Li rEHA Z15 rRHA Z15 rRHA accharom faccharam Saccharom Saccharom Saccharom Ssaccharom YERl3TW acchinem A Ls 215_ RANA CODIE Fiobogical P Taccharom You can add a gene association file to the list by pressing Add 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 header information will be displayed in the center window You can select multiple gene association files The Transfer GO Species Name to Nodes can be used to apply the species name taxon found in the selected Gene Association file to the nodes of the currently selected network This may be an important feature if the nodes of your network do not have a species attribute set You can can see the current network s nodes and species attribute for the nodes in the left hand window You can see the GO symbols terms aspects synonyms and taxons species in the bottom window For nodes in your network to map to GO terms either a symbol or synonym of a term must match the node ID step 4 51 Cytoscape 2 3 2 User Manual Once you have fin
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49. d one red one without a view 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 File New Network option it will be shown as a child of the network that it was derived from In this way the relationships between net works 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 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 View Show Hide Network Overview menu The 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 1 Cytoscape 2 3 2 User Manual Command Line Arguments and Properties Command Line Arguments Table 4 Important The command line
50. dentifies your plugin and the plugin will be loaded if the plugin is in Cytoscape s CLASSPATH For example assuming that the class MyPlugin cgi bin moin cgi MyPlugin can be found in the CLASSPATH you could specify the plugin like cytoscape sh p MyPlugin class A final means of specifying plugins is to specify a file name who s contents contain a list of plugin jar files P props lt file gt This option specifies cytoscape properties Properties can be specified either as a properties file in Java s standard properties format or as individual properties To specify individual properties you must specify the property name followed by the property value where the name and value are separated by the sign For example to specify the defaultSpeciesName cyto scape sh P defaultSpeciesName Human If you would like to include spaces in your property simply enclose the name and value in quotation marks cytoscape sh P defaultSpeciesName Homo Sapiens The property option subsumes previous options noCanonicalization species and bioDataServer Now it would look like cytoscape sh P defaultSpeciesName Human P noCanon icalization true P bioDataServer myServer V vizmap lt file gt This option specifies a visual properties file Aside from plugins all options described above can be loaded from the GUI once cytoscape is running Additional command line arguments that are not recognized by the Cytoscape core are passed to t
51. dom 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 special 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 free 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 65 Cytoscape 2
52. e 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 1s otherwise permitted 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 ex plaining 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 Li
53. earchers 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 same 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 co
54. eld 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 induce 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 made 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 dis tribute 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 in terfaces the 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 In 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 Genera
55. ere a number of networks have been loaded and arranged hierarchically is shown below 10 Cytoscape 2 3 2 User Manual Fie Edt Wire abet Layout Fhan Hiig d chiiOox CunsFansel 1 4 E quieres ighid craa Ta Heranri O n a emen mos pfi Cosa 2 Mode Attribute Ergveser s YER 74 TILGS SC YUOLLI206C TAL LGW TALL Rede dtribuee Brower Edge Afiributg rcecar Matwcrik Atiribezin Pecan The network manager top right tree view in CytoPanel cgi bin moin cgi 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 an
56. erver through the File Import gt Ontology Ontology Server menu option Navigation and Layout Navigation 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 c de Ht From Left to Right e Zoom Out e Zoom In e Zoom Selected Region Zoom out to Display all of Current Network Zoom 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 Pan You can pan the network image by holding down the middle mouse button and moving the mouse You can also pan the image by holding down the left mouse button over the blue box in the Network Overview panel in the lower left hand of the Cytoscape desktop Select Click the left mouse button on a node or edge to select that object You can hold down the Shift key to select more than one node edge or you can hold down the left mouse button and drag the mouse to select groups of nodes edges Context Click the right mouse button on a node edge to launch a context sensitive menu with additional information about the node edge Automatic Layout Algorithms 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
57. es For example the following specifies three edges between the same pair of nodes two of type pp and one of type pd 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 edgeType targetName The tag interaction type should be one of RE I LEEN TTET protein protein interaction S ERE EE 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 DE Rd oa protein gt reaction oT reaction gt compound E compound gt reaction GL sedent Tere genetic lethal relationship poudre E protein metabolite interaction ai o EEEE UR EEA metabolite protein interaction 16 Cytoscape 2 3 2 User Manual Even whole words or concatenated w
58. es between 1 and 2 will be painted with a white red color gradient Sample screenshot is below 43 Cytoscape 2 3 2 User Manual Cytescape Deshtop Ease Sc ait File Edi Wer Select Layout Plugins Help gt d tt LOXG eo Sota a ee Lines OE b kthmd CE ee oT OBSBBO BBESBEBEBESBE amp k RAN ranbak EEEERHERB SBEWENEEME ERE l LEE CIES TIT i TEET Msz Attribute roser EEE E waWadeter UHR EHE 8 os Of ETT URENERr um DJ s Pee E MH FFE K CO O A b DPPC m RWERBWRBZHER r m Toot etter pe a amp s kam RR RR RR tt a Mode Arete Rei Dige Arete eene Hk Aibu Beer Welceeng to Cyt dcape 2 3 Left chrk drag te ZON MeEE chek a drag bo PAM Managing Visual Styles All Cytoscape Visual Style settings are initially loaded from a a default file called vizmap props that cannot be altered by users When users make changes to the visual properties a vizmap props file is saved in the session file This means that assuming you save your session you will not lose your visual properties No other vizmap props files are saved during normal operation Saving Visual Styles Visual styles are automatically saved with the session they were created in Before Cytoscape exits you will be prompted to make sure you save the session before quitting It is also possible to save your visual styles in a file separate from the
59. flag generates the help output you see above and exits V Version This flag prints the version number of cytoscape and exits 8 session lt file gt This option specifies a session file to be loaded Since only one session file can be loaded at a given time this option may only specified once on a given command line The option expects a CyS cytoscape session file It is customary although not necessary for session file names to contain the cys extension N network file This option is used to load all types of network files SIF GML and XGMM L files can all be loaded using the N option You can specify as many networks as desired on a single command line e edge attrs lt file gt This option specifies an edge attributes file You may specify as many edge attribute files as desired on a single command line n node attrs file This option specifies a node attributes file You may specify as many node attribute files as desired on a single command line m matrix file This option specifies a data matrix file In a biological context the data matrix consists of ex pression data All data matrix files are read into node attributes You may specify as many data matrix files as desired on a single command line p plugin file This option specifies a cytoscape plugin jar file to be loaded by cytoscape This option also subsumes the previous resource plugin option You may specify a class name that i
60. fter Y DL 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 YDLO0O The 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 descriptive name Numerical Filter 54 Cytoscape 2 3 2 User Manual Manage Falters Numeric Attribute Filter T Create new filter Remove selected filter Filter Name Node gal IRGexp 1 0 Available Filters Select graph objects af type Node Fs E Node gallRGexp 1 0 pal4RGsig Edge nulle D O With a value for numeric attribute F pal AGexp Node canonicalName YOL qgal4RLGexp Node Topology thatis gt E 1 0 gal ORsig Boe 35M 1 gal 1RG5ig gal amp ORexpn Apply selected filter 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 S Remove selected filter j Filter Name NodeTopolaqy Available Filters Select nodes with i neighbors Node UM RGsig lt 0 0010 within distance 1 Edge ridi 0 0 Node canonkalName WO Node Topology that pass the filter Node
61. h aeo onto node on rhe carat Ph Vici Eb Qu ROM crei a pa ride and Rhe peras B Co bererana 2 7 The Menus File The File menu contains most basic file functionality File Open for opening a Cytoscape session file File gt Save for saving a session file File Import for importing data such as networks and attributes File Export for exporting data and images File Print allows printing File Quit closes all windows of Cytoscape and exits the program File New creates a new network either blank for editing or from an existing network Cytoscape 2 3 2 User Manual Edit Wiew Select L I eu Open Ctrl O Ctri Ctri Shift que Save Az Im port Export CO uit Ctri Edit The Edit menu contains Undo and Redo menu items which undo and redo edits made in the Attribute Browser and the Network Editor There are also options for creating and destroying views graphical representations of a network and networks the network data not yet visualized as well as an option for deleting selected nodes and edges from the current network All deleted nodes and edges can be restored to the network via the Edit gt Undo menu item The Edit Menu also supports Preferences editing for properties and plug ins via a Preferences Dialog Sei View Select Layout Plugins Help Unda Ctrl Redo Ctrl Y Create Views Alt Destroy wiew Ctrl Wy Destroy Network Ctr hift
62. he PlugIn cgi bin moin cgi PlugIn modules Please refer to the documentation for each specific PlugIn cgi bin moin cgi PlugIn for more details 13 Cytoscape 2 3 2 User Manual Cytoscape Properties Table 6 Important If you have used previous versions of Cytoscape you will notice that handling of properties has changed The most important change is that properties are no longer saved by default to the current directory or to your home cytoscape directory Properties are stored by default in Cytoscape Session files The cytoscape props file still exists in the cytoscape directory but is only written to when the user explicitly requests that the current settings be made the defaults for all future sessions of Cytoscape Unless you have something important in your cytoscape cyto scape props file your best bet will be to delete the file and use the defaults The Cytoscape Preferences Dialog accessed via Edit Preferences has sections for general properties display editing and plugins specification via the properties mechanism Preferences are now stored in Cytoscape session files Any changes made to properties while running Cytoscape will be saved to the current session when you save the session If you do not save the session export the properties File Export or set them as defaults see below the properties will be lost and the next time Cytoscape starts defaults will be used Cytoscape properties are displayed
63. in the screenshot 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 real number floating point or boolean Attributes can be deleted using the Delete Attributes button NOTE Deleting attributes removes them from Cytoscape not just the attribute browser To remove attributes only from the browser simply unselect the attribute using the Select Attributes button 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 23 Cytoscape 2 3 2 User Manual then paste into a spreadsheet application Each attribute browser panel has a button for importing new attributes J The Node Attribute Browser panel has additional buttons for loading Gene Expression attribute matrices M and for selecting Gene Ontology GO terms 3 as node attributes The Ontology selection button is only available if an Ontology Server has been imported You can import an Ontology s
64. 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 attribute matrix file using the Cytoscape menu options File Import Attrib ute Expression Matrix to bring up the import dialog box or by specifying the filename using the m option at the command line If you use the command line input you must enter your expression data by node ID If you use the dialog box then you can either load expression data by node ID the default option or can optionally select a node attribute to use in assigning your expression data to your Cytoscape nodes If you do use a node attribute then 1 the attribute should already be loaded and 2 the node attribute value must match the first column in your matrix file FOR EXAMPLE For the sample network file sampleData galFiltered sif 1 Load a sample gene expression data set using the menu File gt Import Attribute Expression Matrix In the res ulting file dialog box in the field labeled Please select an attribute or expression matrix file select sampleData galExpData pvals The identifiers used in this file are the same ones used in the network file 19 Cytoscape 2 3 2 User Manual sampleData galFiltered sif so you do not need to touch the field labeled Assign values to nodes using A few lines of this file are shown below GENE COMMO
65. ished specifying the options click on finish The OBO file and gene_association files specified in this panel will be automatically loaded This will then open up the Ontology Mapper dialog DOglalagir in Lacal 4D Server GO Dale xs AEE Dara force OG Trg Molecular Furic itu CO Menger Funzrion end B5 The Ontology Mapper is used to reduce the number of node attributes created from the gene ontology Selecting a term in the left hand column and clicking the gt gt button will select that term to create an attribute for You can unselect a term using the button The Apply All button will select all terms for attribute creation In most cases Apply AII should be used to import all GO Terms for the network Otherwise only subset of GO Terms in the tree is imported Once the desired terms have been selected click the OK button This will create node attributes for all selected GO terms If you select some GO Terms in the right side window nodes with the GO Terms will be shown in the Node AttributeBrowser cgi bin moin cgi AttributeBrowser By right clicking on a GO Term in the GO Data as Attributes window you can search the GO Term in AmiGO this function requires internet connection and a web browser The GO terms will now be visibile in the Node Attribute Browser by clicking on the Select button If you would like to choose deifferent GO terms from the same gene association file you do not need to re import the files Instead
66. 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 When Cytoscape is started the Attribute Browser appears in the bottom Cytopanel This browser can be hidden and restored using the F5 key or the View Show Hide attribute browser menu option Like other Cytopanels the browser can be undocked by pressing the little icon in the browser s top right corner CytoPanel e Node Attribute Browser LS GOR gallRGexp gallRGsig YERO74W 0 262 1 8517E 5 YMLO2 4W 0 551 5 9725E 11 YILOGSC 0 313 7 7038E 6 3 YOL120C 0 409 1 7242E 7 YHRA74W 0 816 7 175E 11 YGR254W 0 737 6 5621E 11 Ei j Node Attribute Browser Edge Attribute Browser Network Attribute Browser To swap between displaying node edge and network at isibutes use the tabs on the bottom of the panel Node Attribute Browser Edge Attribute Browser and Network Attribute Browser The attribute browser displays attributes belonging to selected nodes and or edges and the currently selected network 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
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68. l 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 distinguishing 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 make exceptions 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 15 BECAUSE THE LIBRARY IS LICENSED FREE OF CHARGE THERE IS NO WARRANTY FOR THE LIB RARY TO THE EXTENT PERMITTED BY APPLICABLE LAW EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT HOLDERS AND OR OTHER PARTIES PROVIDE THE LIBRARY AS IS WITHOUT WARRANTY OFANY KIND EITHER EXPRESSED OR IMPLIED INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF
69. lette 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 cgi bin moin cgi CytoPanel 1 is shown below EY yip mute bubus in CutoP are I ue At bait e merr S Woche iriste Brimir m iuh Berber Herh ute Eier s Vidal 4 PAM To edit an existing network just select the Editor tab in CytoPanel cgi bin moin cgi CytoPanel 1 To start editing a new network use the File New Network menu item The figure below shows the editor with palette defined by Default visual style 45 Cytoscape 2 3 2 User Manual E Cyitecape Deckiog Mew Sesion Pe Cd o wee aet Lem Phawu Hip E m ess 3 nt er i dihat wo ana 1 NT C 4 Hij E fe fx r erk Eeibo nd pUriusr ape Editor EL d rd he a rh cei and dep a eiga from Tue poniente nnb Fa Creed To nonna iag maba efh ani eij drag w ean fhe sera onic A nod on bhs taraa bhan nae panre a merd rode and check he mone d Tees bed Idy Ceo are 1 hue Ahit Doerr o Made Wbitate Ber Edge riue Bremer Hh r oen A ETT a DR Dos 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
70. lid values defaultSpeciesName PleaseSpecif y Species name This value must match the name in the cgi bin moin cgi PleaseSpecify first line of the file specified in the bioDataServer s manifest for synonyms e g for yeast synonyms specify Saccharomyces cerevisiae bioDataServer PleaseSpecif y annotation manifest and other manifest file locations cgi bin moin cgi PleaseSpecify plugins comma separated list of jar files containing plugins or URL s to jar files containing plugins e g http serv er my plugin jar 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 The specification of plugins to be loaded into Cytoscape at startup time is also supported in cytoscape props and ac cessible in this dialog under the Plugins section In this special case the plugins property specifies a comma separated list of jar files or URLs to jar files containing plugins This property is parsed and presented and managed in the Plugins table as at left Setting Default Properties It is possible to alter the default properties for Cytoscape In the Cytoscape Preferences Dialog accessed via Edit Preferences edit any preferences then click the Make Current Cytoscape Properties Default checkbox in the Default Cytoscape Properties section of the dialog This will save any properties to the cytoscape directory contained in your home direct
71. ly selected filter Creating Filters 53 Cytoscape 2 3 2 User Manual The Create new filter button brings up the Filter creation dialog box shown below rFilter types r Filter Type Description Numeric Filter Select nodes or edges based on the value of a string Filter text attribute Topology Filter Boolean Meta Node Interacti Edge Interactic m C OK R C colo we ALZA The important thing to realize when creating a filter 1s that the filter does not do anything by itself Once created the filter must be run String Filter Manage Filters Sing Partem Filter Create new filter Remove selected filter Filter Name od eanenicaliame FDL Available Filters Select qeaph objects of type Node H Mods Pulls Edge null 0 0 with a value for text attribute Canonical Nase 4 Made canceicalName VOL h z 3 l NodeTapoloqy that marches the pattern YOL Beaded nde La Apply selected filter i 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 a
72. 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 60 Cytoscape 2 3 2 User Manual Use the Cytoscape b command line 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 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 the GO XML FTP ftp ftp geneontology org pub go xml page Download the latest go Y Y Y YMM 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 gt goOntology txt See below for Python script listing Obtain the association file for your organism GO maintains a list of association files for many
73. n red and green where red represents a low expression ratio and green represents a high expression ratio with thresholds set for the gallRGexp experiment bundled with Cytoscape in the sampleData galExpData pvals file See sample screenshot below 37 Cytoscape 2 3 2 User Manual eos Cytoscape Dessrop New Session File Ed Wiew Select Layout Plugins Help a dt LOX GS s BT AAA gall isend sif Php i Medes lagen Ei DE 5 0 eaw Mice Attribute Breaser E ws DON E i Edge Amiha Greater Hk Aribi Berea Welceeng to Coscia 2 3 Left chrk drag te ZOOM Merck a dra bo RAN 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 A network 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 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 interactio
74. name manually 55 Cytoscape 2 3 2 User Manual 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 Running filters Any available filter can be run by pressing the Apply selected filter button When a filter is applied and multiple 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 LinkOut The LinkOut cgi bin moin cgi LinkOut plugin provides a mechanism to link nodes to external web resources within Cytoscape Right clicking on a node item in Cytoscape view opens a popup menu with a list of web links The external links are specified in the 1inkout props file which includes a number of default links such as Entrez SGD 1HOP Google as well as a number of species specific links In addition to the default links users can customize the LinkOut cgi bin moin cgi LinkOut menu by adding or removing links without the need to restart Cytoscape or reload the network External links are listed as key value pairs in the linkout props file where key specifies the name of the link and value is the search URL The LinkOut menus are organized in a hierarchical structure that is specified in the key All key terms start with the keyword linkouturl For example the following entry linkouturl yeast
75. neli Mea da 79 gt os i Caren 1 Apoptetis cud ro Metan s Beaux Plugin Lo wede Details Nodes 10A 1 selexbedi Laos 191 00 veberze The user can then chose to resize hide or float the left CytoPanel cgi bin moin cgi CytoPanel For example in the screenshot below the user has chosen to float the CytoPanel cgi bin moin cgi CytoPanel e ee tA OKA G Basic Usage Cytoscape 2 2 includes three CytoPanels cgi bin moin cgi CytoPanels CytoPanel cgi bin moin cgi CytoPanel 1 appears on the left CytoPanel cgi bin moin cgi CytoPanel 2 appears on the bottom and CytoPanel cgi bin moin cgi CytoPanel 3 appears on the right By default only CytoPanel cgi bin moin cgi 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 cgi bin moin cgi PlugIns currently installed in your Cytoscape distribution CytoPanels cgi bin moin cgi CytoPanels can be shown or hidden by selecting the desired menu item within the CytoPanels cgi bin moin cgi CytoPanels menu or by entering the proper keyboard accelerator short cut in order for the keyboard short cuts to work the Cytoscape Desktop must have the focus 47 Cytoscape 2 3 2 User Manual jw CPanel ceby eee In addition CytoPanels cgi bin moin cgi CytoPanels can be floated or docked by selected the icon at the top eli corner
76. nnect the genes present in different data sources even if they have different names as long as those names are recognized by the synonym server 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 usually done in Cytoscape by specifying the species name on the command line with the P option cytoscape sh P defaultSpecies Name Saccharomyces cerevisiae or by editing the properties in the Preferences Dialog Edit Preference The automatic canonicalization of names can be turned off using the P option cytoscape sh P canonicalizeName false or by editing the properties in the Preferences Dialog Edit Preferences 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 ca nonical names as defined by the synonym table Loading Gene Expression Attribute Matrix 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
77. ns to the color red Cytoscape includes a large number of visual attributes These are summarized in the tables below 38 Cytoscape 2 3 2 User Manual Table 11 Visual Attributes Associated with Nodes Node Color Node Border Color Node Border Type The following options are available l m E ES Node Shape The following options are available O 2 Bie Li LAE TELA AE NekSuewihawWigioehnde Node Label te text iren Rode Font nodefonrandsize 0000 sual Attributes Associated ings Edge Color Edge Line Type The following options are available l IL Edge Source ArrOW The following options are available et YT elle Edge Target Arrow The following options are available Pee EE r E EU r3 59 xpo Dp uA a Welt Tvl eaNL Elaa Ege Label he eabel foreach ee ge Font edee fontandsze OOOO O Global Visual Properties 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 Map
78. oat Window control in the upper right corner of the CytoPanel cgi bin moin cgi CytoPanel If you select this control e g on the attribute browser panel you will now have two Cytoscape windows the main window and a new window labeled CytoPanel cgi bin moin cgi CytoPanel 2 similar to the one shown below b CytoPanel 2 Node Attribute Browser SUUS Ip gallRGexp gallRGsig YERO74W l 8517E 5 Y MLO2 4M E 6 9725E 11 YILOGSC 31 7 FO28E 6 YOL120C 1 7242E 7 YHR174W 81 7 l75E 11 YGR254W IX amp 5521E 11 j Node Attribute Browser Edge Attribute Browser Network Attribute Browser i Note that CytoPanel cgi bin moin cgi CytoPanel 2 now has a Dock Window control If you select this control the window will dock onto the main window Cytoscape 2 3 2 User Manual Cytoscape also has an editor that enables you to build and modify networks interactively by dragging and dropping nodes and edges from a palette onto the main network view window The Node shapes and Edge arrows on the palette are defined by the currently used Visual Style To edit a network just select the Editor tab on CytoPanel cgi bin moin cgi CytoPanel 1 An example of an editor with the palette contained in CytoPanel cgi bin moin cgi CytoPanel 1 and defined by the BioMoleculeEditor Visual Style is shown below Fe Ede Da Select Layout Viewslesten Pigi CytnPaneh Help Pbi i t
79. ords may be used to define other types of relationships e g geneFusion cogInfer ence 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
80. ory You should only do this if you want specific properties to apply to all of your Cytoscape sessions You can rely on the Cytoscape session file to maintain the properties used for that particular session so making certain properties default is not necessary to save the properties Building and Storing Interaction Networks Cytoscape reads an interaction network in three ways a simple interaction file SIF or sif format a standard format known as Graph Markup Language GML or gml format and an XML standard called XGMML extensible graph markup and modelling language SIF specifies nodes and interactions only while GML and XGMML store 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 or XGMML format in future Cytoscape sessions SIF GML and XGMML are text files and you can edit and view them in a regular text editor Additionally GML and XGMML are 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 interaction sets into a larger network o
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82. pdf Cytoscape 2 3 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 galFiltered cys Sample session file created from datasets above 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 annotation 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 PlugIns 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
83. per continuous graph attributes are mapped to visual attributes Depending on the visual attribute there are two types of continuous mappers 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 continuous to discrete mapper for example all values below 0 are mapped to square nodes and all values above 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 39 Cytoscape 2 3 2 User Manual Table 12 N amp c p 0 X 0 X o C X X pes F oo X eoo pese p p k per KR RNodeFontFanily o X 0 N uSu 0 X X Edge Label Edge Font Family Edge Font Size Legend Table 13 Mapping is not supported for specified visual property 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 Visual Styles Tutorials Tutorial 1 Creating a Basic Visual Style To create a new visual style select the View Open Viz Mapper menu item or select the color wheel icon in the main button bar You will now see a new Visual Styles dialog box shown below Visual Styles Visual Styles default T Define New Duplicate Rename Delete Close 40 Cytoscape 2 3
84. periment is identified by its experiment name given in the first line Optionally significance measures such as P values may be provided These values generated by many microarray data analysis packages indicate where the level of gene expression or the fold change appears to be greater than random chance If you are using significance measures then your expression file should contain them in a second set of columns after the expression values The column names for the expression significance measures should match those of the expression values exactly For example here is an excerpt from the file galExpData pvals in the Cytoscape sampleData directory GENE COMMON gallRG gal4RG gal80R gallRG gal4RG gal80R YHROSIW COX6 0 034 0 111 0 304 3 75720e 01 1 56240e 02 7 91340e 06 YHR124W NDT80 0 090 0 007 0 348 2 71460e 01 9 64330e 01 3 44760e 01 YKL181W PRS1 0 167 0 233 0 112 6 27120e 03 7 89400e 04 1 44060e 01 YGRO72W UPF3 0 245 0 471 0 787 4 10450e 04 7 51780e 04 1 37130e 05 This indicates that there is data for three experiments gall RG gal4RG and gal8 0R These names appear two times the first time gives the expression values and the second gives the significance measures For instance the second line tells us that in Experiment gall RG the gene YHRO51W has an expression value of 0 034 with significance measure 3 75720e 01 Some variations on this basic format are recognized see the formal file format specification below for more
85. 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 18 Cytoscape 2 3 2 User Manual Affymetrix directly measure expression values without a comparison The file consists of a header and a number of space or tab delimited fields one line per gene with the following format Identifier CommonName valuel value2 valueN pvall pval2 pvalN Brackets indicate fields that are optional The first field identifies which Cytoscape node the data refers to In the simplest case this is the gene name exactly as it appears on the Cytoscape canvas case sensitive Alternatively this can be some node attribute that identifies the node uniquely such as a probeset identifier for commercial microarrays The next field is an optional common name It is not used by Cytoscape and is provided strictly for the user s conveni ence With this common name field the input format is the same as for commonly used expression data anaysis packages such as SAM http www stat stanford edu tibs S AM The next set of columns represent expression values one per experiment These can be either absolute expression values or fold change ratios Each ex
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87. ppear that looks like this dt Quick Tour of Cytoscape When a network is loaded Cytoscape will look something like the image below Cytoscape 2 3 2 User Manual oy A Curezcane Deskrep Dew Storer y F r Ed Wire Sahi Layout Phage rip Ad HbA LOX Om CyraFarsel 1 S Fjoutmarennar 5 Hera n Bitraak Hedef Deige r Dyes iii 2 Mode Attribute Emrat TIER 74 TILGS SC TOLI206C TAL Lew TrSL PORC Rede Ammit Eroweer o dga Atiritutm rome Mrtwcrk Ariba Peter The main window here has several components 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 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 cgi bin moin cgi CytoPanels You can undock any of these panels by clicking on the Fl
88. r add new interactions to an existing data set The main dis advantage is that this format does not include any layout information forcing Cytoscape to re compute a new layout of the network each time it 1s loaded Lines in the SIF file specify a source node a relationship type or edge type and one or more target nodes 15 Cytoscape 2 3 2 User Manual nodeA lt relationship type gt nodeB nodeC lt relationship type gt nodeA nodeD lt relationship type gt nodeE nodeF nodeB nodeG nodeY relationship type nodeZ A more specific example is nodel typeA node2 node2 typeB node3 node4 node5 node0 The first line identifies two nodes called nodel and node2 and a single relationship between nodel 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 same nod
89. r by specifying a file containing the links cytoscape sh P new_linout props or as individual properties cyto scape sh P linkouturl yeast SGD http db yeastgenome org cgi bin locus pl locusV ID Any links defined on the command line will supersede the default links To remove a link from the menu simply delete the property from the Edit amp 8594 Preferences menu Acknowledgements Cytoscape is built with a number of open source 3rd 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 Graph INterface librarY a k a GINY Information is available at http csbi sourceforge net e JDOM Information is available at http www jdom org e JUnit Information is available at http junit org JGoodies Looks Information is available at http www jgoodies com freeware looks index html e Piccolo Information is available at http www cs umd edu hcil jazz Type Specific Collections Library from Sosnoski Software Solutions Inc Information is available at ht tp www sosnoski com opensrc tclib e Xerces Java XML parser Information is available at http xml apache org xerces j CLI command line parser Information is available at http jakarta apache org commons cli FreeHEP library Inform
90. rag Selects Nodes b Edge Invert selection Al A Hide selection ANH Select all mod s and edges CrrH Alt A E i Show AI Alt Shift H Deselect All Nodes and Edges Cur AI4 Shift A Select all edaes AlT A M Use Fitters F Deselect all edges Alt Shift g Smooth selected edges Straighten zelected edges Rotate 29 Cytoscape 2 3 2 User Manual ef 360 Rotate Selected Modes Only The Layout Rotate menu opens the Rotate dialog Rotate will either rotate the entire network or a selected portion of the network The image below shows a network with selected nodes rotated 1 8 1 4 12 Scale Selected Nodes Only 30 Cytoscape 2 3 2 User Manual The Layout Scale menu opens the Scale dialog Scale will scale the position of the entire network or of the selected portion of the network Note that only the position of the nodes scale not the node sizes Node size can be adjusted using the VizMapper cgi bin moin cgi VizMapper The image below shows selected nodes scaled PRU CP PEE UP EUR OPEP DPI S EPIS PP UPPER UP EEE EEEE AAE E UP PUE QOPUPUE Sa I ilt if dtr etude iota utis Praia rie etel inu atta ruunt toatl utu igtur ltutlur detur ud ost AE T fO e e tuu imculetuiinu tius AA antur t etit A E PEREP REETA EE aa CIE E E EEEE re P a a e r z T rE I 4 r i ra P n E r p y
91. refer to a different or perhaps non existent edge The following is an example edge attributes file InteractionStrength YALOO1C pp YBRO43W 0 82 YMRO22W pd YDL112C 0 441 YDL112C pd YMRO22W 0 9013 21 Cytoscape 2 3 2 User Manual Cytoscape treats edge attributes as directional so note that the second and third edge attribute values refer to two dif ferent 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 n and e options or via the File Import 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 Node and edge attributes are attached to nodes and edges NOT to networks If two different networks have the same nodes then those nodes will have the same attributes Even 1f a network 1s loaded after attributes have been loaded 1f the nodes or edges found in the new network already exist then any existing attributes will be applied to those nodes Detailed file format Advanced users Every attribute file has one header line that gives the
92. 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 cgi bin moin cgi InstallAnywhere For one step installation go to http www cytoscape org click Download Cytoscape and follow the on screen instructions 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 0S X cytoscape bat Script to run Cytoscape Windows LICENSE txt Cytoscape GNU LGPL License Cytoscape2 3Manual
93. s cytoscape v2 2 annotation manifest Please press the Finish button to load BioDataServer If you selected Cytoscape BioDataServer cgi bin moin cgi BioDataServer in the first step you need to specify manifest file which lists ontology and annotation files to load Then click on finish All data files will be loaded into Cytoscape For more information about manifest file and how to create it please read the section below 58 Cytoscape 2 3 2 User Manual 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 003673 Gene_Ontology 003674 molecular_function partof 0003673 008435 anticoagulant isa 0003674 016172 antifreeze isa 0003674 016173 ice nucleation inhibitor isa 0016172 016209 antioxidant isa 0003674 045174 glutathione dehydrogenase ascorbate isa 0009491 0015038 0016209 0016672 004362 glutathione reductase NADPH isa 0015038 0015933 0016209 0016654 017019 myosin phosphatase catalyst partof 0017018 A second example KEGG pathway ontology curator KEGG type Metabolic Pathways 90001 Metabolism 800 Carbohydrate Metaboli
94. s the EDGE_TYPE of the edge most recently added defaulting to DefaultEdge cgi bin moin cgi 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 Delete Selected Nodes and Edges menu item You can recover any nodes and edges deleted from a network by selecting the Edit gt Undo 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 CytoPanels What are CytoPanels cgi bin moin cgi CytoPanels 46 Cytoscape 2 3 2 User Manual CytoPanels cgi bin moin cgi CytoPanels are floatable dockable panels designed to cut down on the number of pop up windows within Cytoscape and to create a more unified user experience For example in Cytoscape 2 1 the cPath PlugIn cgi bin moin cgi PlugIn enables users to click on a node and immediately view node details in a pop up window Now with CytoPanels cgi bin moin cgi CytoPanels we can now show these node details in an embedded CytoPanel cgi bin moin cgi CytoPanel The image below shows a screenshot of the latest BioPAX PlugIn cgi bin moin cgi PlugIn When you click on a node the node details appear directly in the left CytoPanel cgi bin moin cgi CytoPanel en rn F Lyla Labi kiog File EG CHEI SE LS THRE Plugins LBP i
95. session file To do this navigate to the File Export Vizmap property file menu and choose the file the properties should be saved to This feature can be used to share visual styles with other users Importing Visual Styles To import existing visual styles navigate to the File Import Vizmap Property File menu option and select a vizmap props file Imported properties will supplement existing properties or override existing properties if the prop erties have the same name You can also specify a visual properties file using the V command line option cytoscape sh V myVizmap props Visual properties loaded from the command line will override any default properties 44 Cytoscape 2 3 2 User Manual Default Visual Styles It is possible to change the default visual properties for all sessions of cytoscape To do this navigate to the Edit Preferences menu check the Make Current Visual Styles Default box in the Default Visual Styles section and click Ok This will save the current visual styles as a vizmap props file to your cytoscape directory found in your home directory These visual styles will be loaded each time Cytoscape is started Editing Networks Using Cytoscape s Editor you can build and modify networks interactively by dragging and dropping nodes and edges from a palette onto the main network view window The palette contains a set of shapes for nodes and arrows for edges The shapes on the pa
96. sm isa 90001 800 Lipid Metabolism isa 90001 800 Energy Metabolism isa 90001 800 ucleotide Metabolism isa 90001 0 0 0 80 Amino Acid Metabolism isa 90001 80 etabolism of Other Amino Acids isa 90001 80 etabolism of Complex Carbohydrates isa 90001 1 3 2 4 5 6 7 0 0 0 0 0 0 0 The format has three required features 1 The first line contains two parenthesized assignments for curator and type In the GO 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 root ontology named Gene Ontology type al1 tells you that all three ontologies are included in that file 1 Following the mandatory title line there are one or more category lines each with the form number0 name isa partof numberl number2 1sa and partof are terms used in GO they describe the relation between parent and child terms in the ontology hierarchy 1 The trailing blank before each left square bracket is not required it is an artifact of the python script that creates these files 59 Cytoscape 2 3 2 User Manual 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 Mycob
97. t level of detail is always chosen regardless of what is currently being displayed on the screen 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 GALA gene s biological process is described 48 Cytoscape 2 3 2 User Manual 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 transcription 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
98. talls 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 more than the cost of performing this distribution 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 singl
99. ter 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 section 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 sourceName edgeType targetName 22 Cytoscape 2 3 2 User Manual To set an attribute for the edge defined by this interaction the matching line in an attributes file should look like sourceName edgeType targetName value 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
100. 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 Finally software patents pose a constant threat to the existence of any free program We wish to make sure that a company cannot effectively 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 free
101. to load navigate and assign annotation terms to nodes in a network In version 2 3 Cytoscape has enhanced the Gene Ontology Server Wizard which enables users to select a local ontology and annotation files from the user interface Although 2 3 remains 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 shtmlstont 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 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 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
102. ttom section of the menu lists a variety of layout algorithms which automatically lay a network out Layout Pete ae Help Rotate scale Align and Distribute C toscape Layouts P JGraph Layouts p iE yFiles Cytoscape 2 3 2 User Manual Plugins The Plugins menu has menu items or choices added by plugins that have been loaded such as Import BioPAX Document from file Plugins Search cPath Merge networks Table 3 Note A list of available Cytoscape PlugIns cgi bin moin cgi PlugIns with descriptions is available online at ht tp cytoscape org plugins2 php Help 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 context sensitive selection Context Sensitive By selecting Context Sensitive menu item and then selecting a GUI component the help related to the selected item is launched The About menu item displays information about the running version of Cytoscape Contents Fi Context Sensitive Shift F1 About Network Management Cytoscape 2 3 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 wh
103. ually in tegrate 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 Cytoscape 2 3 2 User Manual 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 Acknowledgements acknowledgements below What s New in 2 3 Cytoscape version 2 3 contains several new features plus improvements to the performance and usability of the software These include e A much faster rendering engine Cytoscape can now render at interactive speed graphs with over 100 000 nodes and edges
104. y org go G0 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 if m2 goodElements 1 id m2 group 1 name m2 group 2 isaIDs m3 re findall cregex3 term for ref in m3 isalDs append ref m4 re findall cregex4 term partofIDs for ref in m4 partoflDs append ref flatFilePrint id name isaIDs partofIDs else badElements 1 print gt gt sys stderr no match to m2 print gt gt sys stderr Vn npess np sAn np np term Q print gt gt sys stderr goodklements np np d np np goodElements Q print gt gt sys stderr badElements np np d np np badElements Script 1 parseAssignmentsToFlatFileFromGoaProject py import sys def fixCanonicalName rawName for instance trim YBRO85W ANC3 to YBR085W bar rawName find if bar lt 0 return rawName return rawName bar 63 Cytoscape 2 3 2 User Manual def fixGoID rawID bar rawID find 1 return rawID bar def readGoaXrefFile filename lines open filename read split n 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 ipi
105. yer is chosen in such a way that minimizes the number of edge crossings This algorithm is available from the Layout yFiles Heirarchical menu item 26 Cytoscape 2 3 2 User Manual 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 This algorithm is available from the Layout yFiles Organic menu item 27 Cytoscape 2 3 2 User Manual Several other alignment algorithms including a selection from the JGraph project http jgraph sourceforge net are also available under the Layout menu Manual Layout The simplest method to manually layout a network is to click on a node and drag the node If you select multiple nodes all of the selected nodes will be moved together Edge Handles A little known feature If you select an edge and then Ctrl left click on the edge an edge handle will appear This handle can be used to change the shape of the line To remove a handle simply Ctrl left click on the handle again 28 Cytoscape 2 3 2 User Manual EJ oalFitere sit ERES UU oe eB The Select Edges menu has two menu items that provide further control Smooth Selected Edges turns an edge consisting of line segments into a smoothed bezier curve and Straighen Selected Edges turns a curved edge back into line segments Layout Plugins Help Mouse D
106. you can pass the jar file to Java directly using the command java Xmx512M jar cytoscape jar p plugins The Xmx512M flag tells java to allocate more memory for Cytoscape and the p plugins option tells cytoscape to load all of the plugins in the plugins directory Loading the plugins is important because many key features like layouts filters and the attribute browser are included with Cytoscape as plugins in the plugins directory See the Command Line chapter for more detail In Windows it is also possible to directly double Cytoscape 2 3 2 User Manual click the jar file to launch it However this does not allow specification of command line arguments such as the location of the plugin directory 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 Cytoscape Table 2 Important Note For the application to work properly all files should be left in the directory in which they were unpacked The core Cytoscape application assumes this directory structure when looking for the various libraries needed to run the application If you are adventurous you can get creative with the CLASSPATH and or the cyto scape jar manifest file and run Cytoscape from any location you want Cytoscape Window When you succeed in launching Cytoscape a window will a

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