MiMI Plugin User Guide - NCIBI - National Center for Integrative
Contents
1. Eggene type F Kegg gene A Locustag q fal IY A Note Other plugins used earlier in your Cytoscape session may leave behind attributes that don t apply to MiMI Plugin data When you are done click anywhere outside the list MiMI Plugin User Guide April 2010 Page 9 clea SNCIBI 5 Select genes or gene interactions to ote their attributes in the Data Panel see Nu Selecting Genes and Gene Interactions ager Component Description Function regulating synaptic membrane exocytosis 2 metal ion binding GO0 004687 2 protein binding cell junction GO 0030054 cytoplasm GO 00 SH3 and multiple ankyrin repeat domains 1 protein binding GO 0005515 SHANK1 cAMP dependent protein kinase complex GO protein kinase cAMP dependent catalytic alpha ATP binding G0 0005524 cAMP dependent pro PRKACA mara a a M Panel a OS Node Attribute Browser Edge Attribute Browser Network Attribute Browser Importing your own attributes To add your own attributes to the Data Panel you can import an attribute file The file Must be a text file or a Microsoft Excel 97 2003 workbook file xls If a text file Attributes columns must be tab separated Records rows must be on their own line Attribute names column headings are optional One column must be a key column for example Gene Symbol to map to a key attrib2. National Center for Integrative Biomedical Informatics PAPONCIBI MIMI Plugin User Guide 2010 The University of Michigan This work is supported by the National Center for Integrative Biomedical Informatics through NIH Grant 1U54DA021519 01A1 ita SNCIBI CONTENTS Contents Overview About data sources Workflow overview Installing Cytoscape and the MIMI Plugin Launching Cytoscape and the MiMI Plugin from the Web Installing Cytoscape and the MiMI Plugin on your local computer Entering Gene Information Option 1 Load a file containing gene symbols Option 2 Enter a list of gene symbols Additional options Choosing Attributes for Display in the Data Panel Choosing attributes provided through MiMI Importing your own attributes Rearranging attributes in the Data Panel Navigating a Network Navigating among networks Navigating within a network Locating genes or gene interactions within a network by searching Locating genes or interactions using the Data Panel Selecting Genes and Gene Interactions For more information Accessing Gene and Gene Interaction Information Linking to gene literature through Gene2MeSH Linking to detailed information on MiMI Web Linking to gene interaction literature through BioNLP Linking to other data sources Matching Pathway Graphs Using SAGA Working with Networks Expanding a network on a gene node Collapsing an expanded gene node Destroying a network MiMI Plugin User Guide
3. Data Type LCN2 String Integer Floating Point Boolean COA teas i tek ok Cheiee UGTi Al l List LE O S Les List Delimiter is x Key Matched 0 Other aok Cance 5 To map your key column to the key attribute first click Show Mapping Options and then select the column from the Primary Key dropdown Show mapping options EET baiiiakiiiiitamminiisaij V Show Mapping Options Show Text File Import Options ays ID V Case Sensitive Annotation File to Attribute Mapping Key Column in Annotation File Key Attribute for Network Primary Key djy Gene Name Alias Column Attribute Name Data Type w ID 7 O Gene Name lt 4 string M p Value A es Float fa p Value B 12 Float 0 term _ Selected key column attribute is highlighted MiMI Plugin User Guide April 2010 Page 14 ae 3NCIBI 6 Select the corresponding key attribute in the existing network Select the matching key attribute in the existing network Advanced V Show Mapping Options Show Text File Import G Annotation File to Attribute Mapping Key Column in Annotation File Primary Key Ap Gene Name Alias Column Attribute Name Data Type E C Gene Name p String a I p value A SF g Preview Excel Workbook Left Click Enable Disable Column Right C l h Map_loc 7 Click Import at the bottom of the dialog box 8 To view your at
4. Query genes nearest neighbors 2 For What to retrieve select one of the following options examples show resulting networks for entering a list of the gene symbols CP HFE SLC39A14 and FTL Query genes nearest neighbors 26 nodes 32 edges MiMI Plugin User Guide April 2010 Page 7 all Elka SNCIBI Interactions among query genes include at least 2 genes 2 nodes 1 edge Query genes neighbors neighbors 4 607 nodes 28 221 edges Nearest neighbors shared by more than one query genes include at least 2 genes 2 nodes 1 edge 3 Click Search CHOOSING ATTRIBUTES FOR DISPLAY IN THE DATA PANEL Attributes of genes nodes and gene interactions edges you have selected in the network appear in the Cytoscape Data Panel MiMI Plugin User Guide April 2010 Page 8 all Cita INCIBI Choosing attributes provided through MiMI To choose which attributes to view i 3 4 To choose attributes for gene nodes click the Node Attribute Browser tab in the Data Panel for gene interaction edges click the Edge Attribute Browser tab Click the Select Attributes icon in the Data Panel toolbar Data Panel fol Select Attributes Select the attributes you want displayed in the Data Panel Node Attribute Browser Edge Attribute Browser Data Panel Z Chromosome E Component Description Function Gene Name
5. the complete KEGG pathway that was matched click the Link to KEGG Picture link tam MiMI Plugin User Guide April 2010 Page 34 Cita INCIBI WORKING WITH NETWORKS Expanding a network on a gene node You can expand the current network to the nearest neighbors of a gene node Original network l WY WWW S 1 Double click a gene node the expansion seed 2 If the number of additional gene nodes exceeds 30 Cytoscape displays the number and asks if you want to continue Click Yes or No 3 If expansion continues e The network expands adding the nearest neighbors of the expansion seed e The network view may be redrawn and the expansion seed may appear in a different location e On the Network tab in the Control Panel the number of nodes and edges is updated MiMI Plugin User Guide April 2010 Page 35 ita SNCIBI Expanded network am Nien ai wa ST 6a a LX 8 E KD bo ad i ee Symbols appearing in a network expansion Expansion seed node selected Expansion seed node unselected Expansion neighbor selected Expansion neighbor unselected MiMI Plugin User Guide April 2010 Page 36 all lied SNCIBI Collapsing an expanded gene node To collapse an expanded gene node double click the expansion seed The network returns to its original state Note For best results if you have further expanded a network by expanding on an expan
6. was attributed to a more efficient association of HLA H chains with human than 24 2 BSTRACT HFE B2M with munne beta 2 microglobulin which apparently allowed a more rapid transport of the HLA molecules from the endoplasmic reticulum to the Golgi apparatus Previously hepatic iron overload resembling that in hereditary hemachromatosis HH has been found in beta 2 microglobulin knockout beta 2m mice 9234244 ABSTRACT HFN 2M HLA H associates with beta 2 microglobulin MATFRIALS AND METHODS We have semienced the endine recinn and narts nfintrans nf T Click to view the PubMed abstract of an article 892038384 ABSTRAQ HFE 2M Linking to other data sources You can access gene and gene interaction information from numerous external data sources using LinkOut menus in Cytoscape Linking to external sources from the network view 1 In the Cytoscape network view right click a gene node or interaction edge 2 Move to the LinkOut menu 3 Choose a data source from the LinkOut submenus MiMI Plugin User Guide April 2010 Page 29 ee 3NCIBI For example selecting LinkOut gt Entrez gt Gene Visual Mapping Bypass r Use Web Services LinkOut Database MIMI Plugin Reactome MetScape Model OrganismDB gt Array Express Ensembl Gene View F KEGG J All Databases Global search by free keyword Interaction Databases Structure iHOF t Pubmed Other Biological DE H Ontology Pr
7. 00211 Hemochromatosis HFE BRITE hierarchy SSDB Ortholog Paralog Gene cluster __GFIT_ Pfam MHC I Cl set DUFS12 Peptidase Cs PROSITE IG MHC IG LIKE Motif A Hh Other DBs NCBI GI 4504377 NCBI GeneID 3077 OMIM 235200 HGNC 4886 HPRD 01993 Ensembl ENSGOOO00010TO4 UniProt B2CKL 030201 LinkDB L All DBS Structure PDB 1867 1DE4 _ Thumbnails Jmol j l BA seq 348 aa AA seq J DE search MGPRARPALDLLLMILOTAVLOGRLLRASHS LAYLEIMGASEQDLGLSLFEALGYYD YDHESRRVEPRTPAVSSRISSOMWLOLSOSLEGWDAMETYVYDEIWT IMENANASRE l a amie 1 TEGCEMOEDM SIE GYWRY GY DGQBHLEECPDTLDWEAREPRRUP TS EWE RHE TH MATCHING PATHWAY GRAPHS USING SAGA Use SAGA Substructure Index based Approximate Graph Alignment with the MiMI Plugin to compare and match selected nodes and edges to a database of known biological pathways MiMI Plugin User Guide April 2010 Page 32 lead SNCIBI Select a subset of a MiMI network in Cytoscape with the following requirements Select at least 2 but no more than 50 gene nodes Select at least 1 but no more than 80 gene interaction edges SS _ lt m J N LAT ZINN Mf fie WW Right click any selected node and select MiMI Plugin gt SAGA gt Do SAGA Choose multiple nodes amp edges MIMI Plugin Query SAGA Select either KEGG Human Pathways or All KEGG Pathways For Percentage of
8. April 2010 Page iii WW OW P NO wl Ul 0 16 17 17 18 19 23 24 26 26 26 26 28 29 32 35 35 37 37 AA SNCIBI Saving and Reopening a Session Saving a session Reopening a session Using MIMI Plugin Specific Features in Cytoscape Restoring the MiMI visual style Annotations Accessing the MiMI Plugin legend MiMI Plugin selection behavior MiMI Plugin User Guide April 2010 Page iv 37 37 37 38 38 39 40 41 clea SNCIBI OVERVIEW About data sources The MiMI Plugin provides access to data in the MiMI database from within the Cytoscape bioinformatics network visualization tool The MiMI database integrates molecular data from numerous protein interaction databases including BIND Biomolecular Interaction Network Database http bond unleashedinformatics com CCSB Center for Cancer Systems Biology http ccsb dfci harvard edu web www ccsb DIP Database of Interacting Proteins http dip doe mbi ucla edu dip Main cgi GRID General Repository for Interaction Datasets http www thebiogrid org HPRD Human Protein Reference Database http www hprd org IntAct http www ebi ac uk intact main xhtml KEGG Kyoto Encyclopedia of Genes and Genomes http www genome jp kegg MDC Max Delbruck Center http www mdc berlin de en index html MINT Molecular INTeraction database http mint bio uniroma2 it mint Welcome do PubMed http www ncb
9. Matched Nodes specify the percentage of selected nodes that must match a known biological pathway for the subset of nodes to be considered a successful match with the pathway The default is 10 MiMI Plugin User Guide April 2010 Page 33 lz 3NCIBI 5 Click Query The results appear in a new browser window or tab The Query Result Result for the Query MiMIPlugin2SAGA Total Execution Time s 0 030983 Number of Matches 4 excluding self matches Matches Overview Match No Match Graph Name Nodes Edges Graph Distance Matching Nodes Match 1 path hsa04610 50 67 Complement and coagulation cascades 21 00 3 out of 8 Match 2 path hsa04620 62 79 Toll like receptor signaling pathway 24 00 2 out of 8 Match 3 path thsa04012 53 85 ErbB signaling pathway 25 00 2 out of 8 Match 4 paththsa04630 22 27 Jak STAT signaling pathway 25 00 2 out of 8 6 Click a link in the Match No column to view a visual representation of the match between selected network nodes in your query and the matching graph Go Back to Matches Overview _ Match 1 path hsa04610 350 nodes 67 edges Complement and coagulation cascades Graph Distance 21 00 3 out of 8 nodes match Link to KEGG Picture with the matching nodes highlighted Blue rectangles indicate matching genes query MiMIPlugin2SAGA Thick blue lines indicate od c2 matching interactions Thin red line connects matching genes 7 To view
10. Protein Interaction Types And Annotations show hide a Provenance Sources show hide a lt lt Literature associating interactions show hide P val ZN National Institutes of Health grant U54DA021519 NC BI ve _ a Copyright 2008 by The University of Michigan lt www ncibi org For support and questions email mimi help umich edu For more information on using MiMI Web see the MiMI Help and Support page Linking to gene interaction literature through BioNLP To access summaries of abstracts related to a gene interaction through BioNLP Natural Language Processing of Biology text 1 Right click a gene interaction edge and select MIMI Plugin gt BioNLP PE eee MiMI Plugin User Guide April 2010 Page 28 eA SNCIBI 2 A list of matching sentences appears Click to view the Gene Details page on MiMI Web m Cytoscape MiMI Plugin Query BioNLP DA Welo 3 r A m 25 Sentences Raiatea To p Ana B2M From BioNLP SORT GINGLE tLICK Sentences by semantic gf y May take several minutes for long lists Computed by MEAD a cepsoid tsed extractive summarization system PubmedID Section Symbol Syrtbol tence Stable recombinant water soluble complexes of HLA A and HLA B27 were reconstituted 1517560 ABSTRACT HFE B2M from 125 labeled beta 2 microglobulin beta 2m a synthetic peptide and HLA H chain fragments expressed as inclusion bodies in the Escherichia coli cytoplasm This effect
11. after using the MCODE plugin with MCODE visual style y N 1 In the Cytoscape Control Panel click the VizMapper tab You may need to use the scroll arrows at the top of the Control Panel to see the tab 2 For Current Visual Style select MIMI Control Panel twork VizMapper Editor Filters Current Visual Style MMI MiMI Plugin User Guide April 2010 Page 38 all clea SNCIBI 3 The MiMI visual style is restored Network after resetting the MiMI visual style Annotations You can add public or private annotations to a gene node or gene interaction edge For more information e See Adding your own node edge annotation in the MiMI Plugin tutorial on the NCIBI website e Explore on your own by right clicking a node or edge and selecting MIMI Plugin gt User Annotation gt Add Your Annotation You will need to sign up and then sign in to create your own annotations MiMI Plugin User Guide April 2010 Page 39 clea SNCIBI Accessing the MIMI Plugin legend In the Cytoscape Control Panel click the MiMI Legend tab You may need to use the scroll arrows at the top of the Control Panel to see the tab VizMapper Editor Filters MIMI Legend Initial seed node Neighboring node Expansion seed Expansion neighbor User annotation Normal Interaction User annotation Note If you open a saved Cytoscape session the MIMI Legen
12. ar region GO 0005576 collagen G0 0005581 collagen MiMI Plugin User Guide April 2010 Page 22 lz 3NCIBI Locating genes or interactions using the Data Panel You can locate specific gene nodes and interaction edges in the network view by selecting their attributes in the Data Panel 1 Click the Node Attribute Browser or Edge Attribute Browser tab in the Data Panel Select attribute rows for the nodes or edges you want to locate e Click on a single row to highlight a single gene or interaction e Use Ctrl click to select multiple discontiguous rows e Use Shift click to select a range of contiguous rows The corresponding genes or interactions are highlighted in green in the network view Data Panel A Ow _ Gene Name Component cellular_component GO 0005575 cytoplasm GO actin filament G0 0005984 cytoplasm GO 00057 mitochondrial alpha ketoglutarate dehydrogenase 730 C7 extracellular region G0 0005576 membrane attac 930 cDI9 integral to plasma membrane GO 0005887 plas integral to plasma membrane GO 0005887 mem integral to membrane GO 0016021 plasma mem integral to membrane GO 001 6021 plasma mem Node Attribute Browser Edge Attribute Browser Network Attribute Browser MiMI Plugin User Guide April 2010 Page 23 all lied SNCIBI Note This procedure helps you visually identify individual nodes or edges from among those a
13. ation in additional data sources Linking to gene literature through Gene2MeSH To access PubMed articles related to a gene through matching MeSH subject headings 1 Right click a gene node and select MIMI Plugin gt LinkOut NCIBI gt Gene2Mesh 2 The Gene2MeSH page for the selected gene appears in a new browser window or tab uy ie Gene Annotation with MeSH Terms __ NCiBI About Gene2MeSH HFE Search by O Gene MeSH Term Both Riel A rs Homo sapie Substances only Gene2MeSH Search examples brca2 Prostatic Neoplasms history HFE 109 109 MeSH headings found matching gene symbol HFE lookup gene or MeSH heading at NCBI M view interactions in Mi E dovmload tab delimited results Gene Symbol eadin TaxID P Value MeSH Qualifier Gene Description PubMed HEE M 9606 o genetics hemochromatosis 392 HEE M re co s 9606 0 genetics hemochromatosis 456 HEE M HAHN Proteins 9606 o genetics hemochromatosis 457 HES M Iron 9606 3 8973051127583E 281 metabolism hemochromatosis 168 ETN A a nN map Ae EE A ee a a n E E a For more information about using Gene2MeSH see the Gene2MeSH About page Linking to detailed information on MiMI Web To access more detailed information about a gene or gene interaction 1 Right click a gene node or gene interaction edge and select MIMI Plugin gt LinkOut NCIBI gt MiMIWeb 2 The Details page in MiMI Web for the selected gene or int
14. ching attribute values appear in a dropdown list Data Sources 1 Query genes nearest neighbors m oo a a5 ra W a ee tere asa ee eg ee a 5 oe oe L Ste d E MiMI Plugin User Guide April 2010 Page 20 eA SNCIBI 4 Select an item in the list to locate the node or edge Cytoscape zooms to the item and selects it Note Using Search to select a gene interaction also selects the connected genes Example Locating genes on the same chromosome chromosome 13 1 In the Configure Search Options dialog select the Chromosome attribute for genes nodes E Configure Search Options for FZP1 AFAM1 CF M H Smeal Search Nodes Edges Select Attribute Attribute Description No description available Sample Attribute Values MiMI Plugin User Guide April 2010 Page 21 Cita INCIBI 2 Type in the Search box and select 13 with 6 matching genes a PEB FZP1 AFA a Data Sources 1 Query genes nearest neighbors 1 24 hits 10 7 hits 20 hits 123 hits is epee aaea 3 The 6 genes are selected FZP1 AFAMI CF M Homo sapiens All Molecule Types All Data Sources 1 Query genes nearest neighbors aig E an 4 The Data Panel displays attributes for the selected genes Data Panel cytoplasm GO 0005737 mitochondrion G60 00057 39 condensed nuclear chromosome basement membrane GO 0005 extracellul
15. ching the application from MiMI Web again Installing Cytoscape and the MIMI Plugin on your local computer 1 Install Cytoscape on your computer For more information go to e The Cytoscape website at http cytoscape org or e The NCIBI Virtual Workshop page at http portal ncibi org gateway virtual workshop html 2 After Cytoscape is installed start the application 3 To install the MiMI Plugin select Plugins gt Manage Plugins from the Cytoscape menu MiMI Plugin User Guide April 2010 Page 3 aE INCIBI 4 Under Available for Install click the box to expand the Network and Attribute I O group Plugins available For download From Cytoscape E Currently installed 20 Theme 1 d Core 14 _ Network and Attribute I O 4 MClick to expand the Network Uncategorized 1 em a ini and Attribute I O group Theme 1 Analysis 4 unication Seripting 6 I Network and Attribute I O 35 Other 18 Network Inference 7 L Functional Enrichment 13 roe p NESSoOgeS Install PC eee MiMI Plugin User Guide April 2010 Page 4 i 3NCIBI 5 Find and click the most recent version of the MiMI Plugin a Manage Plugins Plugins available for download From Cytoscape GFML Flugin w of GPML Plugin v 0 8 i a GPML Plugin v 0 9 GPML Plugin v 1 0 ont InbAckW SClient v 0 66 ee wf MiMIplugin v 2 2 S f MiMIplugin v 3 0 S Mil plugin v 3 01 NCBIC
16. d tab does not appear in the Control Panel until you use the MiMI Plugin to enter gene information in a new query MiMI Plugin User Guide April 2010 Page 40 lead SNCIBI MIMI Plugin selection behavior When you select nodes and edges they are highlighted in the network view and the attributes of the selected nodes or edges are displayed on the Node Attribute Browser or Edge Attribute Browser tab in the Cytoscape Data Panel Selected edge B gt AS Selected node Data Panel Oo Gene Name Description Gene type Kec APOAT 335 apolipoprotein A protein coding hsa ONECUTI 3175 one cuthomeobox1 protein coding hsa UGT1IAI 54658 UDP glucuronosyltyafSferase 1 family polypeptide protein coding hsa UGTIA3 54659 UDP glucuronge fitransferase 1 family polypeptide protein coding hsa Attributes of selected nodes Secesepenegenesnneeenrercco cerrsrrretrrenerttiess wre MiMI Plugin User Guide April 2010 Page 41
17. eraction appears in a new browser window or tab MiMI Plugin User Guide April 2010 Page 26 lea SNCIBI Fora gene Download as PSI MI QA Gene Details hemochromatosis HFE Homeo sapiens Gene Type protein coding Chromosome 6 a Map Locus 5921 3 Locus Tag null Other Names HFE e dJ221016 10 1 HFEL HH a HLA H e MGC103790 Descriptions Authorized Gene Description hemochromatosis Other descriptions e MHC class I like protein HFE o hemochromatosis protein o hereditary hemochromatosis protein HLA H Query Interactions Molecule Details for Gene Entry HFE Geneld 3077 show hide wy Protein Interactions 3 gene interactions found show hide Literature Mined Interactions 6 Interactions found show hide Literature on gene HFE 584 publications found Gene Attributes Cellular Components MHC class I protein complex cytoplasm integral to plasma membrane membrane plasma membrane show hide ra About MIMI Biological Processes antigen processing and of peptide antigen via MHC class I cellular iron ion homeostasis immune response ion transport iron ion transport protein complex assembly receptor mediated endocytosis ee ie ie lee AA MiMI Plugin User Guide April 2010 Page 27 eA SNCIBI For an interaction Se Pathways show hide GO GO Terms show hide t W
18. i nim nih gov pubmed Reactome http www reactome orgd Each of these data sources is updated on its own schedule The MiMI Plugin reflects updates as they become available For information on additional data sources available through the MiMI Plugin see the About MiMI page MiMI Plugin User Guide April 2010 Page 1 all lied SNCIBI Workflow overview With the MiMI Plugin for Cytoscape you can visualize interactions between genes or proteins and interactively explore the network of relationships among them The basic steps in the workflow include 1 2 Enter a set of genes You can type in a list of genes or upload a file of gene symbols Select gene and gene interaction attributes Choose which attributes to display in a table as you work with a visual network graph including any attributes you import into Cytoscape Explore the visual network and table of attributes e Expand and collapse the network e Sort and filter data e Visualize your data in a wide variety of network layouts provided by Cytoscape e Use color size and other effects to visually reflect a set of attribute values Select genes or gene interactions to access more detailed information about them e Link out to additional information about selected objects e Access summaries of abstracts mined from the research literature through natural language processing BioNLP related to a selected gene interaction e Compare a
19. ide April 2010 Page 12 File Size 17 KBytes eA SNCIBI 4 If your attribute file includes attribute names as column headings select Show Text File Import Options and then select Transfer first line as attribute names Select Import Options Show Mapping Options V Show Text File Import Options Import everything Key is always ID Advanced Text File Import Options Delimiter Preview Options I Show all entries in the fi Attribute Names Net Transfer first line as attribute names Start Import Row lt Comment Line L Preview Select Transfer option Excel Workbook Left Click Enable Disable Column Right Click E Sheeti w Gene Nam Wp ValueA wp ValueB GO term CP 0 0070 iron homeostati _HFE 0 0010 iron homeostati SLCSSA14 iron homeostati First row values become attribute names MiMI Plugin User Guide April 2010 Page 13 eA SNCIBI If your attribute file does not include column headings for attribute names name them by right clicking the default column headings and entering a new attribute name Right click default column heading Excel Workbog Left Click Enable Disable Column Right Click Edit Column L Preview ee ee ei Shashi Set Attribute Name and Type l2 columni Attribute Name and Type Then enter a new attribute name CP _ Attribute name For Column 1 ents HFE Column 1 __SLCSSAI4 FTL Attribute
20. lient v 0 7 a s NCBIEntrezGeneUserInterface v 0 5 of PICRClient v 0 2 a SessionForWeb v 3 1 ven SessionForWeb v 3 2 ves SFLDLoader v 1 2 yf SFLDLoader v 1 3 f StringWSClient v 1 1 Lad Guinernathwave Pliinin w i r l T Tl Messages 6 Click Install Change Download Site Show outdated Plugins Category Network and Attribute I O Description MIMI Cytoscape plugin retrieves molecular interactions from Michigan Molecular Interactions MIMD database and displays the interaction network with Cytoscape MIMI gathers and merges data from well known protein interaction databases including BIND DIP HPRD Refseq swissProt IPI and 7 When installation is complete click Close A MIMI Plugin option is added to the Cytoscape Plugins menu ENTERING GENE INFORMATION 1 To begin a Cytoscape session with the MiMI Plugin start Cytoscape 2 Select Plugins gt MIMI Plugin gt Query from the Cytoscape menu 3 Choose one of these methods to specify genes Option 1 Load a file containing gene symbols Use when you have a large number of gene symbols The file e Must be a text file e Must include a list of official gene symbols one per line MiMI Plugin User Guide April 2010 Page 5 ea 3NCIBI Example CP HFE 5LC394A14 LCN TF UGT1A1 NPC B4GALT1 PLD4 SGP11 EDG3 1 Click the From File tab Welcome to MiMI Plugin 3 0 1 Enter Gene Symbols From File Quer
21. lready selected in the network view but does not create an actionable Subset Cytoscape functions will continue to operate on all selected nodes or edges not just those you have located using this procedure SELECTING GENES AND GENE INTERACTIONS Use Cytoscape methods to select nodes representing genes and edges representing interactions between genes Selecting a single gene Click the gene node A selected node appears in yellow Selecting a single gene interaction Click and drag a rectangle around any segment of the gene interaction edge then release the left mouse button A selected edge appears in red MiMI Plugin User Guide April 2010 Page 24 Cita INCIBI Selecting multiple genes and or gene interaction edges Hold down the Shift key while clicking on nodes and or edges and or while dragging rectangles around them Selecting genes and gene interactions within an area Click and drag a rectangle around any area of the network to select the nodes and edges within that area Selecting any part of a node or edge selects the entire node or edge MiMI Plugin User Guide April 2010 Page 25 ee 3NCIBI For more information For detailed information on selecting nodes and edges in a network see the Cytoscape User Manual ACCESSING GENE AND GENE INTERACTION INFORMATION In addition to viewing gene and gene interaction attribute values in the Cytoscape Data Panel you can link to related inform
22. ong multiple open networks use the Network tab in the Cytoscape Control Panel Total number of nodes edges Control Panel ain Y Current network Network with no eer network window 7P1 AFAMI CF M H2a5ta2 1963 231 110 0 90 0 1468 336 Number of selected nodes edges To view a network click on its entry on the Network tab Note The default network title is a list of the queried genes followed by the options you selected for the query To edit a title right click the network entry and select Edit Network Title For more information about working with networks and the Network tab see the Cytoscape User Manual MiMI Plugin User Guide April 2010 Page 17 clea SNCIBI Navigating within a network To navigate within a network use the network overview pane at the bottom of the Network tab in the Cytoscape Control Panel File Det View Select Layout Plugin Help ee Qaagags Li Control PIi Go ere Ty Meteor WoMappa EANO Piare MME Legand Met eats hades Lipa FHEA PAJE how Li Dy Ota bt Network overview pane Area visible in main network window a a zi 1 rs Leet a p a a Me a Pi z E l p i F k i Omia Panai iD Capri aa ai Parmin pare Alger Figi heheaimnent Harshan cerni OO DONA a Quinine nuriyyide Hinang protein i protain aip OTP bandia eaa OTR aa B OO oe OMAN 1067 milancome 0004247 0 manmerane 000016 guanine nuchigide Binding protein oO
23. otein EBI Tools H OMIM UniProt H Nucleotide Search Engines results in the following Entrez Gene page for the selected gene ra co S ENtrez Gene All Databases PubMed Nucleotide Protein Genome Structure OMIM Search Gene for 3077 uid Limits Preview index History Clipboard Details Display Full Report Sendto C 4 HFE hemochromatosis Homo sapiens enelID 3077 Summary Official Symbol HFE Official Full Name hemochromatosis Primary source HGNC 4886 See related Ensembl ENSGOO000010704 HPRD 01993 MIM 235200 Gene type protein coding RefSeq status REVIEWED Organism Homo sapiens lll ll Selig tlle a Bie ts Mabel g MiMI Plugin User Guide April 2010 Page 30 clea SNCIBI Note The external data sources available for genes differ from those available for gene interactions Linking to external sources from the Data Panel When linking to external data sources from the Cytoscape Data Panel you can link to the external source using a specific attribute value However not all attribute values are appropriate for all data sources 1 In the Cytoscape Data Panel right click on the value in the attribute column in the row for the gene or interaction of interest Data Panel ene Name zn LUMKI hsa 3984 cytoplasm G0 0005737 focal Kegg gene Component 3175 ONECUTI hsa 31 75 nucleus G00005634 6927 H F1A hsa 6927 nucle
24. owing Gene Description attributes do not match NADH dehydrogenase ubiquinone 1 beta subcomplex 8 19kDa NADH dehydrogenase ubiquinone 1 beta subcomplex 2 8kDa e For a successful match the search term must match the attribute value from the start of the string you cannot match a substring within an attribute value For example the search term Lysine biosynthesis does not match the following attribute value Citrate cycle TCA cycle path hsa00020 Lysine biosynthesis path hsa00300 D Glutamine and D glutamate metabolism path hsa0047 1 e Search does not support logical operators wildcards or other advanced search features Note For more flexible and powerful searching including logical operators and wildcards you can use the Enhanced Search plugin for Cytoscape For more information see the Analysis group of plugins on the Cytoscape Plugins page To search for genes or interactions 1 Click Configure search options to the right of the Search box in the Cytoscape toolbar MiMI Plugin User Guide April 2010 Page 19 ita SNCIBI 2 Set search options Configure Search Options for FZP1 AFAM1 CF M JH eo Search Nodes Edges Select which attributes to list Select Attribute Select the attribute to search by Sample Attribute Values PREP RXFP4 SERPING VTN TK Click Apply Cancel li Apply 3 Enter a search term in the Search box As you type mat
25. part of your network to a database of known biological pathways Save your session and reopen it later INSTALLING CYTOSCAPE AND THE MIMI PLUGIN You can use the MiMI Plugin for Cytoscape in one of two ways By launching Cytoscape and the MIMI Plugin from MiMI Web With this method you launch a temporary copy of Cytoscape and the MiMI Plugin from a Gene Details page after performing a search on MiMI Web Use this method when you don t have the administrative privileges to install software on your computer You will not have access to other plugins when you use this method By installing Cytoscape and the MIMI Plugin on your local computer With this method you can use other plugins that work with MiMI data such as Shortest Path and MCODE MiMI Plugin User Guide April 2010 Page 2 clea SNCIBI Launching Cytoscape and the MiMI Plugin from the Web To launch Cytoscape and the MiMI Plugin from MiMI Web 1 Go to http mimi ncibi org MimiWeb main page isp 2 On the Free Text Search or List Search tab search for one or more genes For more information on searching in MiMI Web click the Help tab 3 On a Search Results page click a gene link 4 On the Gene Details page click the Cytoscape button near the bottom of the page After launching the Web version of Cytoscape you can do anything described in this User Guide You can save your Cytoscape session on your local computer and reopen it at a later time after laun
26. protein ale OTP b ndis 90000055745 GTPase aci 90000 MAI S826 Caco iO MOST Ir trace Bule GO 000542 Rho guanine nuchoteds archange facto jeEF 81 GTPase acteater acii Ee DOR quay BAHGEF 11 CETT Domai Oe bee Cine manalaa mnie oe aAa A AT aana na A aimed moon icine 1 Piode Attribute Brower Beige Abtribute oa Stor Aiie Browse nn Cyetace 2 6 7 Eoia drag bo Doe Pide my fo PAR To view another part of the network click on the shaded area in the network overview pane and drag it into place To adjust the view magnification use the Zoom tools in the Cytoscape toolbar Q Q e Zoom Out and Zoom In e Zoom Selected Region Make one or more selections using any Cytoscape methods then click this tool to display the region that encompasses all of them a For more information about zooming and using the network overview pane see the Cytoscape User Manual e Zoom Entire Network MiMI Plugin User Guide April 2010 Page 18 Cita SNCIBI Locating genes or gene interactions within a network by searching You can locate and select a specific gene or gene interaction within a network by using the Search feature of Cytoscape You can also use search to find a group of genes or interactions with common attribute values Search is especially useful with large complex networks Limitations of the Search feature in Cytoscape e Fora successful match the search term must match the entire attribute value For example the foll
27. sion neighbor collapse the nodes in the reverse order in which you expanded them Destroying a network To destroy a network you no longer need 1 Make sure you want to destroy the network e Cytoscape will not ask you to confirm the deletion e Destroying the network is irreversible e Note If you want to destroy a network view without destroying the network itself use Destroy View instead of Destroy Network See the Cytoscape User Manual for more information 2 On the Network tab in the Control Panel right click on the network you want to destroy the network does not need to be selected and select Destroy Network SAVING AND REOPENING A SESSION Saving a session To save a Cytoscape session containing one or more MiMI Plugin networks 1 From the Cytoscape menu select File gt Save or Save As 2 Browse to a location for the session file 3 Name the file 4 Click Save Reopening a session To reopen a saved session containing MiMI Plugin data 1 From the Cytoscape menu select File gt Open 2 Navigate to the file location 3 Select the file MiMI Plugin User Guide April 2010 Page 37 eA INCIBI 4 Click Open 5 After Cytoscape reports that the session file was successfully loaded click Close USING MIMI PLUGIN SPECIFIC FEATURES IN CYTOSCAPE Restoring the MIMI visual style You may need to restore the MiMI visual style after using a different plugin that uses its own style Network
28. tic vesicle G0 00301 39 endosome GO 00 TF nucleus G0 0005634 transcription factor TFIID co TAF1 5764 s endoplasmic reticulum G0 0005783 extracellular PTN ext Zoeller ee oo 0005576 MHC class prot DataPanel Drag the column Z O w Componer Gene Name m Integral to membrane G0 00 PUNC E B G CUBN ome 567 extracellular ia Drop the column into position Data Panel ntegral to membrane G00016021 membrane G rush border membrane GO 0031526 endosome ytoplasm GO 0005737 cytosol G60 0005829 m ytoplasm G0 00057 37 integral to plasma memb indocytic vesicle G0 00301 39 endosome GO 00 jucleus G0 0005634 transcription factor TFIID co indoplasmic reticulum G0 0005783 extracellular ixtracellular region GO 0005576 MHC class prot To sort by an attribute click the attribute column heading to sort in the reverse direction click again Data Panel integral to plasma membrane GO 0005 cytoplasmic vesicle 60 0031 410 ende chylomicron 60 0042627 extracellular cytoplasm G00005737 intracellular E cytoplasm G00005737 intracellular E basolateral plasma membrane 60 001 extracellular region GO 00055 7 6 MHC Node Attribute Browser Edge S eee MiMI Plugin User Guide April 2010 Page 16 clea INCIBI NAVIGATING A NETWORK Navigating among networks To navigate am
29. tributes Node 0 Edge Network Input File Select File s Advanced E Show Mapping Options Show Text File Import Options Import everything Key is always ID Case Sensitive Preview Legend BCC EKES Key Attributes 10117 i 10200 A Ce S 103817 M aii 103827 10577 10672 10720 1356 ja Left Click Enable Disable Column Right Click Edit Column Data File Preview Window Import Annotation File gt Import Attribute from Table Data Sources Attributes Input File Node Edge Network File C Users Desktop CytoiHemeAndSphingNoHdgReadiInList xls Advanced Show Mapping Options Show Text File Import Options Import everything Key is always ID V Case Sensitive Preview l Excel Workbook Left Click Enable Disable Column Right Click Edit Column Legend Alias Sheet1 w Column 1 Key Attributes 10117 10200 Column 2 Column 3 Column 4 Gene Name p Value A p Value B GO term 10381 CP 0 038 0 0070 iron homeostatis 10382 HFE 0 011 0 0010 iron homeostatis SLC39A14 0 17 ETL 0 302 0 0070 iron homeostatis iron homeostatis 10577 10672 LCN2 iron homeostatis 10720 TE yr iron homeostatis 1356 Key Matched 0 First 100 entries are loaded for preview eee MiMI Plugin User Gu
30. tributes in the Data Panel click the Select Attributes icon in the Data Panel toolbar and select the attributes which will appear in the panel when you select nodes and edges that have imported attributes associated with them Imported attributes are displayed when matching nodes are selected Data Panel NN a O Py ID Gene Name p Value A pValue B GO term a ii i Component 54658 __ UGTIAI 0 0010 4 0E 4 iron homeostatis endoplasmic reticulum GO 000 10577 NPC 0 34 0 0080 Cholesterol Homeostatis extracellular region GO 000557 3984 LUMKI cytoplasm 60 0005737 focal 0 0010 iron homeostatis cytoplasm G0 00057 37 integr 2512 FTL _ 0 302 0 0070 iron homeostatis ferritin complex G0 0008043 6927 HNFIA nucleus G0 0005634 protein 7037 TFR cytoplasmic membrane bound MiMI Plugin User Guide April 2010 Page 15 clea SNCIBI Rearranging attributes in the Data Panel To reorder attributes in the Data Panel click an attribute column heading and drag it to a new location Click the column integral to membrane G0 0016021 membrane G 8029 brush border membrane GO 0031526 endosome E 7786 cytoplasm G0 0005737 cytosol G0 0005929 m Data Panel cytoplasm GO 0005737 integral to plasma memb TFR2 70138 endocy
31. us G00005634 protein 10720 UGT 2811 hsa 10720 kasii ls sien ae 3077 hsa 3077 E TERC nsa7037 x ER am table Copy Select All Export Search hsa 3077 on the web F 2 Move to the Search on the web menu and choose an appropriate data source from the submenus Ensembl Gene View sn lek EBITools gt ad a UniProt Pi 1D GeneName Kegggene 3 Model Organism DE F Function 3984 LIMK1 hsa 3984 cytoplasm EO 0005737 foca Entrez p FP binding IGO 0005524 metal 3175 ONECUTI hsa 3175 nucleus IGO mona Array Express quence specific DNA binding C 6927 HNF1A hsa 6927 10720 UGT2B11 hsa 10720 Hien binding GO 000551 5 ser Other Biological DB curonosyltransferase activity C 3077 hsa3077_ ae Sian iHOP on ion binding GO 0005506 F elect from table T 7037 TFRG hsa 7037 KEGG I yeast use ORF name i Copy Interaction Databases gt Eia ea Select All Reactome t mouse use NCBI GenelD Ontology HO human use NCBI GeneID d Search Engines b MiMI Plugin User Guide April 2010 Page 31 eA NCIBI For example right clicking the value hsa 3077 in the Kegg gene attribute column and selecting KEGG gt All Species use KEGG ID results in the following KEGG page for the corresponding gene Homo sapiens human 3077 Entry 3077 CDS H sapiens Definition hemochromatosis Disease H
32. ute in the existing network MiMI Plugin User Guide April 2010 Page 10 ee 1NCIBI Excel example Optional column headings i A B C E 1 Gene Name pValue A pValue B GO term 2 CP 0 038 0 007 iron homeostatis Heme metabolism 3 HFE 0 011 0 001 iron homeostatis Heme metabolism 4 SLC39A14 0 17 0 06 iron homeostatis Heme metabolism 5 FTL 0 302 0 007 iron homeostatis Heme metabolism 6 LCN 0 55 0 08 iron homeostatis Heme metabolism T TF 0 6 0 06 iron homeostatis Heme metabolism 6 UGTIA1 0 001 0 0004 iron homeostatis Heme metabolism 9 NPC 0 34 0 008 Cholesterol Homeostatis 10 B4GALT1 0 25 0 003 Sphingolipid Metabolism 11 PLD4 0 36 0 0001 Sphingolipid Metabolism 12 SGP11 0 044 0 009 Sphingolipid Metabolism 13 EDG3 0 016 0 0005 Sphingolipid Metabolism 14 SOAT1 0 37 0 0006 Cholesterol Homeostatis 15 ABCA 0 008 0 004 Cholesterol Homeostatis 16 APOD 0 002 0 001 Cholesterol Homeostatis For information on other importing options see Import Attribute Table Files in the Cytoscape User Manual To import attributes 1 From the Cytoscape menu select File gt Import gt Attribute from Table Text MS Excel eo MiMI Plugin User Guide April 2010 Page 11 clea SNCIBI 2 For Attributes select Node Edge or Network depending on the attributes you re adding and click Select File s Select the attribute type Import Annotation File h p import Attribute able Data Sources At
33. y MIMI Load Gene File 2 Click Load Gene File 3 Browse to the gene file and click Open 4 Continue with Additional options Option 2 Enter a list of gene symbols Use to do a query with a small number of gene symbols 1 On the Enter Gene Symbol s tab enter one or more gene symbols separated by commas Welcome to MiMI Plugin 3 0 1 Enter Gene Symboll s Query MiMI CP HFE SLC39A14 FTL Official Gene Symbols e g csFir cent Homa Sapiens aa All Molecule Types aa All Data Sources What to retrieve 1 Query genes nearest neighbors Search MiMI Plugin User Guide April 2010 Page 6 ee 3NCIBI Additional options 1 Select an organism molecule type and or data source or use the defaults Note Selecting All Data Sources includes all of the other data sources listed in the dropdown as well as additional data sources For a complete list of data sources see the About MiMI page Dialog box after loading a file containing gene symbols MIMI Plugin Use default parameters or change them Al Molecule Types 7 All Data Sources a What to retrieve 1 Query genes nearest neighbors Dialog box after entering a list of gene symbols Welcome to MiMI Plugin 3 0 1 Enter Gene Symbolls From File Query MiMI CP HFE SLC39A14 FTL Official Gene Symbols e g csFir cent Homa Sapiens All Molecule Types All Data Sources w What to retrieve 1
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