1. Pathway Informatics 30 th March, 2016 Ansuman Chattopadhyay, PhD Head, Molecular Biology Information Services Health Sciences Library System University of Pittsburgh ansuman@pitt.edu

2. Biological Pathway Map http://www.hsls.pitt.edu/molbio

3. Pathway Informatics List of Genes Protein-Protein Interaction Database Pathway Map http://www.hsls.pitt.edu/molbio

4. Biological Interaction Network Biological Table Gene List Gene list to pathways http://www.hsls.pitt.edu/molbio

5. Learn How to … 1.Draw Pathway Diagram 2. Search Pathways Databases 3. Search PPI Databases 4. Search Gene Expression Databases 5. Find statistically overrepresented attributes linked to differentially expressed genes

6. Software Learn How to … 1. Draw Pathway Diagram : ePath3D 2. Search Pathways Databases: Infoboosters 3. Search PPI Databases: BioGrid, STRING 4. Search Gene Expression Databases: NextBio 5. Find statistically overrepresented attributes linked to differentially expressed genes: IPA, Enrichr, Metacore, DAVID http://www.hsls.pitt.edu/molbio

7. ePath3D

8. Software Learn How to … 1. Draw Pathway Diagram : ePath3D 2. Search Pathways Databases: Infoboosters 3. Search PPI Databases: BioGrid, STRING 4. Search Gene Expression Databases: NextBio 5. Find statistically overrepresented attributes linked to differentially expressed genes: IPA, Enrichr, Metacore, DAVID http://www.hsls.pitt.edu/molbio

9. Biological Pathways Metabolic Signaling http://www.hsls.pitt.edu/molbio

10. Databases-Pathways  KEGG http://www.genome.jp/kegg/pathway.html Pathway Commons: http://www.pathwaycommons.org/pc/ http://www.pathwaycommons.org/pc/ Ingenuity Pathway Sehttp://www.ingenuity.com/?s=apoptosis#!/api/rest/v1/client/searchPathways?q=apoptosisarch: Sehttp://www.ingenuity.com/?s=apoptosis#!/api/rest/v1/client/searchPathways?q=apoptosisarch: http://www.hsls.pitt.edu/molbio

11. InfoBoosters : Molecular DBs

13. Software Learn How to … 1. Draw Pathway Diagram : ePath3D 2. Search Pathways Databases: Infoboosters 3. Search PPI Databases: BioGrid, STRING 4. Search Gene Expression Databases: NextBio 5. Find statistically overrepresented attributes linked to differentially expressed genes: IPA, Enrichr, Metacore, DAVID http://www.hsls.pitt.edu/molbio

14. PPI Databases http://www.hsls.pitt.edu/molbio

15. What proteins interact with my favorite protein? http://www.hsls.pitt.edu/molbio

16. PPI Databases BioGRID STRING http://www.hsls.pitt.edu/molbio

17. Link to the video tutorial: http://media.hsls.pitt.edu/media/molbiovideos/ppi.swf Resources BioGrid: http://thebiogrid.org/ http://thebiogrid.org/ STRING: http://string-db.org/ http://string-db.org/ - Retrieve interacting partners of a protein of your interest - What proteins interact with human EGFR? -

18. BioGrid http://www.hsls.pitt.edu/molbio

19. BioGrid Search Result Page http://www.hsls.pitt.edu/molbio

20. STRING - Known and Predicted Protein- Protein Interactions  An ultimate resource for finding both predicted and experimental verified PPI  Not limited to human, mouse and rat  Developed at CPR, EMBL, SIB, KU, TUD and UZH CPREMBLSIBKUTUDUZH http://www.hsls.pitt.edu/molbio

21. STRING http://www.hsls.pitt.edu/molbio

22. Software Learn How to … 1. Draw Pathway Diagram : ePath3D 2. Search Pathways Databases: Infoboosters 3. Search PPI Databases: BioGrid, STRING 4. Search Gene Expression Databases: GEO, NextBio 5. Find statistically overrepresented attributes linked to differentially expressed genes: IPA, Enrichr, Metacore, DAVID http://www.hsls.pitt.edu/molbio

23. Gene Lists http://www.hsls.pitt.edu/molbio

24. Gene Lists Microarrays Protein arrays CHIP-chip SNP arrays RNA Seq Literature Search http://www.hsls.pitt.edu/molbio

25. Gene Expression Databases NCBI Gene Expression Omnibus (GEO) EBI ArrayExpress http://www.hsls.pitt.edu/molbio

26. Gene Expression Database http://www.hsls.pitt.edu/molbio

27. Use of GEO Data  http://goo.gl/yD2hR http://goo.gl/yD2hR http://www.hsls.pitt.edu/molbio

28. Generate a gene list http://www.hsls.pitt.edu/molbio

29. Pathway Analysis Control A549 cell + Ethanol (25  mol/L) 48 hr Treated A549 cell + Resveratrol (25  mol/L) 48 hr http://www.hsls.pitt.edu/molbio

30. Retrieve Gene Expression data NCBI GEO EBI ArrayExpress NextBio Research http://www.hsls.pitt.edu/molbio

31. Gene Expression Database http://www.hsls.pitt.edu/molbio

32. Searching GEO http://www.hsls.pitt.edu/molbio

33. Searching GEO http://www.hsls.pitt.edu/molbio

34. Searching GEO http://www.hsls.pitt.edu/molbio

35. GEO2R http://www.hsls.pitt.edu/molbio

36. GEO2R – Experiment to Gene List http://www.hsls.pitt.edu/molbio

37. GEO2R – Experiment to Gene List http://www.hsls.pitt.edu/molbio

38. GEO2R – Experiment to Gene List http://www.hsls.pitt.edu/molbio

40. NextBio Registration https://www.nextbio.com/b/register/register.nb http://www.hsls.pitt.edu/molbio

41. NextBio http://www.hsls.pitt.edu/molbio

42. NextBio http://www.hsls.pitt.edu/molbio

43. NextBio http://www.hsls.pitt.edu/molbio

44. NextBio Search http://www.hsls.pitt.edu/molbio

45. NextBio GeneList http://www.hsls.pitt.edu/molbio

46. RNA-seq Study http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099625

47. http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52778

48. Gene Expression Atlas http://www.ebi.ac.uk/gxa/ http://www.hsls.pitt.edu/molbio

49. Array Express http://www.hsls.pitt.edu/guides/genetics

50. Literature to GeneList GEOGeo2RNextBioGene List http://www.hsls.pitt.edu/molbio

51. Software Learn How to … 1. Draw Pathway Diagram : ePath3D 2. Search Pathways Databases: Infoboosters 3. Search PPI Databases: BioGrid, STRING 4. Search Gene Expression Databases: NextBio 5. Find statistically overrepresented attributes linked to differentially expressed genes: IPA, KPA, Enrichr, Metacore, DAVID http://www.hsls.pitt.edu/molbio

52. Gene Lists to Biology http://www.hsls.pitt.edu/molbio

53. IPA

54. Metacore-KPA

55. http://www.hsls.pitt.edu/molbio

56. GO Consortium http://www.hsls.pitt.edu/molbio

57. GO Annotation Cellular Component Biological Process Molecular Function http://www.hsls.pitt.edu/molbio

58. Copyright restrictions may apply. Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565 Levels of abstraction Gene Ontology (GO)

59. Copyright restrictions may apply. Khatri, P. et al. Bioinformatics 2005 21:3587-3595; doi:10.1093/bioinformatics/bti565 Evolution history of GO-based functional analysis software Development of gene ontology based tools

60. Biological Table Biological List Gene list to Biology Functions Pathways Interaction Networks http://www.hsls.pitt.edu/molbio

61. Pathway Analysis Software NLP Driven PathwayArchitectPathwayStudio Human Curated Ingenuity IPA GeneGO’s Metacore Biobase Explain “ Axin binds beta-catenin, GSK-3beta and APC.” Extracted Facts: Axin - beta-catenininteraction: Binding Axin - GSK-3betainteraction: Binding Axin - APCinteraction: Binding http://www.hsls.pitt.edu/molbio

62. DAVID Bioinformatics Resources http://www.hsls.pitt.edu/molbio

63. DAVID Tools Functional Annotation  Clustering Chart – Term centric Table – Gene centric http://www.hsls.pitt.edu/molbio

64. DAVID http://www.nature.com/nprot/journal/v4/n1/fig_tab/nprot.2008.211_T1.html http://www.hsls.pitt.edu/guides/genetics

65. NIH DAVID http://www.hsls.pitt.edu/molbio

66. http://www.nature.com/nprot/journal/v4/n1/fig_tab/nprot.2008.211_T1.html http://www.hsls.pitt.edu/guides/genetics

68. GEO2Enrichr http://www.hsls.pitt.edu/guides/genetics

69. GEO2Enrichr http://www.hsls.pitt.edu/guides/genetics

70. GEO2Enrichr

72. Cytoscape http://www.hsls.pitt.edu/molbio

73. Hands-on Exercise Use NIH DAVID to uncover enriched pathways associated with the “Alzheimer's gene list” http://www.hsls.pitt.edu/molbio

74. Thank you! Any questions? Ansuman Chattopadhyay ansuman@pitt.edu http://www.hsls.pitt.edu/molbio