1. Copyright OpenHelix. No use or reproduction without express written consent1

2. GeneMANIA Gene Multiple Association Network Integration Algorithm for Fast Gene Function Predictions Materials prepared by: Jennifer M. Williams, Ph.D. www.openhelix.com Updated: Q3 2010 Version 1

3. Copyright OpenHelix. No use or reproduction without express written consent3 GeneMANIA Agenda Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises GeneMANIA: http://www.genemania.org

4. Copyright OpenHelix. No use or reproduction without express written consent4 Introduction to GeneMANIA Use GeneMANIA to: Find new members of a pathway or complex Identify additional genes missed in screens Classify new members of a functional class of proteins Your question is defined by gene list input! List of Genes Gene 1 Gene 2 Gene 3 Gene 4 Gene 5 Gene 6 ? GeneMANIA List of Genes Gene 1 Gene 2 Gene 3 Gene 4 Gene 5 Gene 6 Gene 7 Gene 8 Gene 9… Gene X Plus: Network showing gene links Visual displays of supporting data Scores to aid interpretation of data

5. Copyright OpenHelix. No use or reproduction without express written consent5 GeneMANIA Overview GeneMANIA Advantages: Easy to use Fast and flexible Accurate (e.g. as shown in MouseFunc competition) Learns from gene lists Upload own networks PMID:18613946 PMID: 18613948

6. Copyright OpenHelix. No use or reproduction without express written consent6 Network data sources: data from individual studies datasets from public resources such as: BIND, BioGRID, HPRD, IntAct, MINT, Interologous Interaction Database (or I2D), InterPro, Reactome, Pathway Commons, Pfam and others. GeneMANIA Team and Institution Description Use cases Results advice http://www.genemania.org/pages/help.jsf http://www.genemania.org/pages/people.jsf http://tdccbr.med.utoronto.ca/ http://www.utoronto.ca/ http://www.genomecanada.ca/ http://www.ontariogenomics.ca/

7. Copyright OpenHelix. No use or reproduction without express written consent7 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

8. Copyright OpenHelix. No use or reproduction without express written consent8 Search with Single Gene Easy to use: Pick a species Enter gene(s) Click ‘Go’ click Species: human, mouse, fly, and other model organisms Change species for our example Enter ‘HFR1’ for our example

9. Copyright OpenHelix. No use or reproduction without express written consent9 Single Gene Search Results HFR1 DNA binding Protein binding Transcription Many genes annotated as having similar functions Single gene analyses - based on weighted GO annotation patterns click to expand all gene listings

10. Copyright OpenHelix. No use or reproduction without express written consent10 HFR1 Gene List Search Results expand Different gene list than single gene search Datasets may not be used if they don’t contain relevant information about members of the gene list Multi gene analyses ‘score’ datasets with gene list-specific weights before doing the network analysis

11. Copyright OpenHelix. No use or reproduction without express written consent11 Single Gene vs Gene List Overview Single Gene Example Links based on GeneOntology (GO) terms Gene List Example Links based on collaborative filtering & network weighting of datasets before predicting new gene links Practical Upper Limits for web interface = ~100 GeneMANIA Cytoscape plugin = 100 - 400

12. Copyright OpenHelix. No use or reproduction without express written consent12 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

13. Copyright OpenHelix. No use or reproduction without express written consent13 Display Overview & Interactivity Network Visualization Interacts with Summary Panels link datasets

14. Copyright OpenHelix. No use or reproduction without express written consent14 Network Visualization and Gene Summary entered predicted Interactive Network Visualization and Summary Displays entered predicted click

15. Copyright OpenHelix. No use or reproduction without express written consent15 Network Layout and Functions Network layouts are dynamic GO functional information for nodes

16. Copyright OpenHelix. No use or reproduction without express written consent16 Network Functions, cont. Mouse over to see associated nodes Click to add color to network 1st term both neither

17. Copyright OpenHelix. No use or reproduction without express written consent17 Network Functions, Additional Display Features Changing Function order can change node colors Removing Functions removes node coloring order switched

18. Copyright OpenHelix. No use or reproduction without express written consent18 Network Panel: Drag & Highlight Neighbors Click and drag to move nodes Action menu to highlight neighbors drag select

19. Copyright OpenHelix. No use or reproduction without express written consent19 Network Visualization Panel: Pan & Zoom Controls Pan-zoom area can be hidden from network Slider to control network size Pan view left, right, up, down, or drag Fit graph to screen Decrease or increase network

20. Copyright OpenHelix. No use or reproduction without express written consent20 Network Summary Tab: Additional Features Sort By: name per cent weight (default) Expand: none only top level all Enable: all or none “Sometimes networks used by GeneMANIA to connect all of your input genes are grayed out because the connecting genes they contain score too low to be returned in your query results.”

21. Copyright OpenHelix. No use or reproduction without express written consent21 Gene Summary and Help Tabs: Additional Features Sort By: name score Expand: all none Help Genes

22. Copyright OpenHelix. No use or reproduction without express written consent22 Network Pull-down Menus Pull-down menus for other display options Networks legend for network color coding Functions legend for functions color coding

23. Copyright OpenHelix. No use or reproduction without express written consent23 Network Visualization Panel: Save Menu Query Parameters Composite Network click Gene List Network List Dates & Version

24. Copyright OpenHelix. No use or reproduction without express written consent24 Network Visualization Panel: Save Menu, cont. Interaction List Enriched Gene Annotations Export as text

25. Copyright OpenHelix. No use or reproduction without express written consent25 Network Visualization Panel: Action Menu Reset layout Close tooltips select

26. Copyright OpenHelix. No use or reproduction without express written consent26 Network Visualization Panel: Action Menu, cont. Merge links toggle Hide/Show network labels & pan-zoom controls

27. Copyright OpenHelix. No use or reproduction without express written consent27 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

28. Copyright OpenHelix. No use or reproduction without express written consent28 Dataset Selection # of Gene Results Network weighting human Example gene list Click to run Dataset list, checked sets are selected Networks (Datasets)

29. Copyright OpenHelix. No use or reproduction without express written consent29 Default Human Results select deselect

30. Copyright OpenHelix. No use or reproduction without express written consent30 Alternate Dataset Selection: Results

31. Copyright OpenHelix. No use or reproduction without express written consent31 Default Datasets Effect of Selecting Datasets on Network Selected Datasets Very different networks & color coding

32. Copyright OpenHelix. No use or reproduction without express written consent32 Effect of Selecting Datasets on Gene Predictions Default Datasets Selected Datasets Different predicted gene lists

33. Copyright OpenHelix. No use or reproduction without express written consent33 Data Selection Conclusion Select data type(s) Examine & select specific datasets

34. Copyright OpenHelix. No use or reproduction without express written consent34 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

35. Copyright OpenHelix. No use or reproduction without express written consent35 Network Weighting Example fly search Default datasets Default weighting Datasets: 15/40 co-expression 3/8 physical interactions 2/2 genetic interactions 1/7 co-localization datasets Automatically selected weighting method

36. Copyright OpenHelix. No use or reproduction without express written consent36 Network Weighting: Default Search Results Genes entered: aret, bcd, bic, Bin1, bin3, byn, cad, grk, gt, osk, rno, Ser Genes predicted: aub, BicC, fkh, Lis-1, orb, rn, stet, Su(fu), Syr-delta, ttk Notice percentages

37. Copyright OpenHelix. No use or reproduction without express written consent37 Network Weighting: Selecting Equal Weighting Example fly search Default Datasets Equal weighting Equal by data type Datasets: 15/40 co-expression = 3/8 physical interactions = 2/2 genetic interactions = 1/7 co-localization

38. Copyright OpenHelix. No use or reproduction without express written consent38 Network Weighting: Default Search Results Genes entered: aret, bcd, bic, Bin1, bin3, byn, cad, grk, gt, osk, rno, Ser Genes predicted: aub, BicC, CG30437, fkh, fz3, ken, Lis-1, orb, Sry-delta, stet Notice percentages

39. Copyright OpenHelix. No use or reproduction without express written consent39 Network Weighting: Summary Query-dependent weighting automatic (6+ vs <6 genes) or assigned on gene basis example: initial or standard searches Gene Ontology-based weighting BP, MF or CC example: searching for kinases, or membrane proteins Equal weighting by network or data type example: do not want a bias towards any one type of experiment or dataset

40. Copyright OpenHelix. No use or reproduction without express written consent40 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

41. Copyright OpenHelix. No use or reproduction without express written consent41 Uploading Personal Datasets Help, Upload Uploaded datasets Simple, tab- delimited format Protein Interactions Gene Expression Data

42. Copyright OpenHelix. No use or reproduction without express written consent42 Formatting a Personal Dataset Three columns: Gene 1, Gene 2, Score Save as tab-delimited (.txt) file Upload to GeneMANIA (next slide)

43. Copyright OpenHelix. No use or reproduction without express written consent43 Uploading a Personal Dataset select

44. Copyright OpenHelix. No use or reproduction without express written consent44 Selecting a Personal Dataset

45. Copyright OpenHelix. No use or reproduction without express written consent45 Results with Personal Dataset Included our dataset General Tips user-uploaded networks = any other network equal weighting ensures network appears ask to return more genes

46. Copyright OpenHelix. No use or reproduction without express written consent46 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

47. Copyright OpenHelix. No use or reproduction without express written consent47 GeneMANIA Plug-In for Cytoscape Advanced Visualization Browse Query Results Publication-ready Figures Very Large Gene Lists

48. Copyright OpenHelix. No use or reproduction without express written consent48 GeneMANIA Mailing List scientist@OpenHelix.com

49. Copyright OpenHelix. No use or reproduction without express written consent49 GeneMANIA Citation http://genomebiology.com/2008/9/S1/S4 Also see About > Help or News

50. Copyright OpenHelix. No use or reproduction without express written consent50 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

51. Copyright OpenHelix. No use or reproduction without express written consent51 GeneMANIA Summary From a list of genes to detailed networks in a matter of seconds!

52. Copyright OpenHelix. No use or reproduction without express written consent52 Powerful Advanced Search Options Include/Exclude Datasets Custom Select Network Weighting Format & Upload Your Own Datasets “top performer” according to MouseFunc competition (PMID: 18613946)

53. Copyright OpenHelix. No use or reproduction without express written consent53 GeneMANIA Agenda GeneMANIA: http://www.genemania.org Introduction and Credits Basic Searches Understanding Displays Data Selection Network Weighting Uploading Your Own Dataset Tips and Additional Resources Summary Exercises

54. Copyright OpenHelix. No use or reproduction without express written consent54