1. The AfCS Bioinformatics Laboratory 2002

2. The AfCS Data Coordination and Bioinformatics Laboratory 2002 Goal 1 Acquire, Process, and Disseminate Information

3. The AfCS Website (www.afcs.org) 2002 WebMaster: Stephen Lyon Web related design: Stephen Lyon Brad Kroeger Dawn Cotter Timo Hannay (NPG)

4. The AfCS Website (www.afcs.org) 2002

5. Website Users Anonymous Public Registered Public AfCS Personnel Content Contributors Website Developers Overall Development Molecule Pages Protein Lists Experimental Data Reports Database Search Utilities The AfCS Website 2002

6. Website Content Public Areas About AfCS Data Home Login Membership Molecule Pages Protein Lists Protocols Reports Signaling Maps Sponsors Restricted Areas Access Control Administration Protein List Administration E-mail Aliases Progress Reports View Upload System Committees Message Boards Barcode Data DataScope AfCS Website Content 2002

7. HTTP request from user HTTP response from server Apache mod_perl Static HTML Perl CGI Java servlets Oracle database Access Control Layers 1. Web server layer: General access control for all users of the website 2. Application layer: More specific access control and personalization for users of each application (username can be read from cookie set by Layer 1) 3. Database layer: Database gives different access privileges to each application Overview of Access Control Layers 2002

8. User Request Dynamic Pages Dynamically Generated Static Pages WebServer Access Check User Database Program Access Check Page Types & Access Control 2002

9. The primary purpose of the bulletin board is to facilitate the exchange of ideas, documents and data between Alliance members and provide the public a forum for providing feed back. AfCS Bulletin Board 2002

10. Posting features define by the board administrator or moderator Security features defined by the board administrator or moderator Formatting features user controlled User profile features defined by the user board administrator Searching features AfCS Bulletin Board 2002

12. Topic Views On line documentation Search and administration 2002

14. The AfCS Data Coordination and Bioinformatics Laboratory 2002 Goal 2 Design and Develop a Laboratory Information Management System

15. Lothar Krause Madhusudan Lonnie Sorrels (SWMED) Ron Taussig (SWMED) Dallas Expt. Lab. Yuhong Ning Ilango Vadivelu Peter Morrison AfCS Barcode/LIM System 2002

16. Facilitate Sample Tracking Standardize Data Inputs/Outputs Automate Data Transfer between Labs Maintain Data Integrity AfCS Barcode/LIM System 2002

17. AfCS Data Flow 2002

18. Inputs Cell Prep ID and yields unique treatment and sample IDs. This application also requires a protocol that is tied to the assay for which the sample is created, e.g. Western, Microarray etc. It captures the treatment details including incubation conditions, cell density, ligand and its concentration and time of exposure. This GUI also functions as a query tool. By entering an ID into the ‘Experiment ID’ and clicking on ‘barcode’, it re-loads the data previously submitted for that ID. Treatment GUI 2002

19. Treatment GUI 2002

20. Treatment Tables 2002

21. Barcode GUI 2002

22. Reagent GUI Barcode Ligand GUI Barcode Solution GUI Barcode Protocol GUI Printed protocol with barcode Protocols: Interaction of the GUIs 2002

23. Protocol GUI 2002

24. Solution GUI 2002

25. Reagent, Ligand & Solution Tables 2002

26. The AfCS Data Coordination and Bioinformatics Laboratory 2002 Goal 3 Create Efficient Internet Sites for Deposition, Inspection, and Utilization of Primary and Processed Data 2002

27. AfCS Data Store 2002 Robert Sinkovits Dennis Mock Brad Kroeger Chic Barna Richard Schuermann (Visitor) Yuhong Ning

28. Data transfer from Dallas/Caltech  SDSC Parsing of transfer log files to identify new data Parsing of data files / database loading Generation of graphics, tables, etc. Displaying results for ligand/assay Data Curation Update of ligand screen page Ligand descriptions Data handling 2002

29. Set of four cron jobs (microarray,cAMP, Ca++,Western blot) run each night. Names of newly uploaded files passed as arguments to loader scripts. Log files created so that experiment schemas can be easily repopulated auto-ftp log western master Ca master cAMP master micro master western loader Ca loader cAMP loader micro loader western@afcs Ca@afcs cAMP@afcs micro@afcs Parsing log files / loading db 2002

30. Scripts generate libraries of static images, html, tab- delimited files. Data pulled from experiment and barcode schemas Ligand screen data directories purged and reloaded with new graphics, etc. western@afcs Ca@afcs cAMP@afcs micro@afcs barcode@afcs western process Ca process cAMP process micro process data/western data/Ca data/cAMP data/micro Graphics generation 2002

31. Argument passed to CGI script to specify graphics, etc. to be displayed cal_ligscr.cgi data/Ca AIG_0.3_uM_BC Text, graphics, links, etc. for Ca assay 0.3 uM anit-Ig using B cells Display 2002

32. Ligand screen display (partial) 2002

33. Ca++ display Automatically generated graph of Ca++ time courses for B cells treated with Antigen (Anti-Ig). Curves color coded by experiment. 2002

34. cAMP display Automatically generated bar graph of cAMP assays for B cells treated with Prostaglandin E2. 2002

35. Western blot display Automatically generated graph of phosphoprotein immunoblot results for B cells treated with CD40 Ligand. 2002

36. Western blot display Automatically generated graph of phosphoprotein immunoblot results for B cells treated with IL-4. Large pSTAT6 response plotted on right axis. 2002

37. cDNA display Clicking on cluster returns annotation for all clones belonging to cluster 2002

38. cDNA Analysis Interface 2002 Array display and analysis for AfCS Membersdisplay analysis

39. SWMED SDSC server graphicslogdata cal_master.pl cal_loader.plcal schema cal_graph.plbarcode schema curate.cgi cal_disp.cgi internal.html public.html display.html SRB Data flow overview: Ca++ 2002

40. The AfCS Data Coordination and Bioinformatics Laboratory 2002 Goal 4 Design and Implement the Infrastructure for Molecule Pages Database

41. 2001

42. Joshua Li Yuhong Ning Warren Hedley Brian Saunders TBK Reddy (BW) Andrea Maer (BW) Yousheng Chen Derren Barken (UCSD) Timo Hannay (NPG) Nicole Tindill (NPG) & Dallas AfCS Team The AfCS Molecule Pages 2002

43. A comprehensive literature-derived, object- relational database of signaling molecules Distributed data entry by experts Link to AfCS experimental data A dynamic source of protein interactions with genomic and domain data from other databases Definition of the “Functional State” of each signaling protein 2001 MP Features 2002

44. The author is responsible for entering information about –AfCS protein’s functional states –Interactions of their protein with other proteins, and small molecules –Mutations of the protein, and their consequences and/or phenotypes –Relevant experimental information Molecule Pages – Author-Entered Data 2002

45. “Automated Data” for each protein is provided to both the public and the authors, and can be referenced by the author when entering their own data The types of automated data made available will include: –Summaries of and links to external database records that correspond to, or are related to, the author’s protein (e.g., Genbank, SwissProt and PDB records) Molecule Pages – Automated Data 2002

46. The Molecule Pages website is generated by a 3-tier application The web and middle tiers are Enterprise Java application running on the “Oracle Components 4 Java (OC4J)” application server The database tier is Oracle 8.1.7 System Architecture 2002

47. 2001 Molecule Pages Multi-Tier Infrastructure 2002

48. Ontology: Ontology in the database world associates definition and knowledge about objects contained in the database. The knowledge pertains to properties of the object and its relationships to other objects coded as tables or indexes. E.g., Ion channel: Object properties: sequence, structure, gating, kinetic…etc. Relationships: other channels, physiology, cell locations, diseases…etc. Ontology 2002

49. Database schema for antibody 2002

50. Physical Data Model for Molecule Pages 20012002

51. 2001 Molecule Pages 2002

52. Protein GI Defining protein record (type 0) + Identical sequence records (type 1) + SwissProt discrepancies and their identities (type 1) + SwissProt / TrEMBL variants (type 2) + Clustered sequences and their identities (type 3) + Variants of clustered sequences (type 4) sequence has no defining GI ( LocusLink + CNR ) (CNR) CNR = Combined non-redundant protein database Molecule Page External DB 2002

53. Genbank, Swissprot, and LocusLink records referenced through protein database links Specific fields of interest included in annotation database schema (e.g. Genbank feature information, Swissprot external database references, LocusLink chromosomal information) Records obtained from in-house relational databases or flat files External Database Records 2002

54. Protein Database Links + Component Databases Schema 2002

55. Locus Link Schema 2002

56. Domain, Motif, and Family Schema 2002

57. Blast Schema 2002

58. Status Submit_Date Revised_Date Approval_Date Reviewers Editor Privileges The AfCS Bioinformatics Laboratory 2002

59. 2001 Functional State 2002

60. Substrate Binding Covalent Modification Protein Dissociation Protein Interaction FS1-5 DO ALL STATES Do i= 1, FS1; if more Do j = 1, FS2; if more Do k = 1, FS3; if more Do l = 1, FS4; if more Do m = 1, FS5; For State i, is X an R, E, C, T, A, TF or combination Launch state specific quantitative table List interactions Lookup Mutant List Do Tables Change? If yes go to top; else add mut ID Protein Localization FS1-5 2001 Procedure for launching context-specific state tables/interactions 2002

61. 2001 FUNCTIONAL STATE 2002

62. 20012002

63. DELETION deletion_id position_start position_end VA12 N10 SUBSTITUTION substitutionid position_start deleted_sequence added_sequence VA12 N10 VA300 VA3000 PROTEIN_MUTATION_LOOKUP prot_mutation_type long_description short_description VA12 VA150 VA40 INSERTION insertion_id insertion_position inserted_sequence VA12 N10 VA990 PROT_MUTATION prot_mut_id func_consequence note type_cpd_omutation mut_species VA12 VA95 VA300 VA25 COMPOUND_ORG_MUTATION cpd_mutation_id cpd_mutation_name phenotype note link_jackson VA12 VA25 VA300 VA120 COMPOUND_ORG_MUT_LOOKUP cpd_mutation_type short_description long_description VA12 VA40 VA150 FUSION fusion_id added_sequence VA12 VA3000 POINT point_id old_aaname new_aaname point_position VA12 VA10 N10 20012002

64. REF REF_ID J_ABBREV ENTRY_ID TITLE REF_CREATOR REF_TYPE AFCS_KEYWORD SUBJECT ABSTRACT CONTRIBUTOR START_PAGE END_PAGE VOL ISSUE PUBLICATION_DATE REF_FORMAT LANGUAGE IDENTIFIER VARCHAR2(12) VARCHAR2(25) VARCHAR2(12) VARCHAR2(95) VARCHAR2(25) VARCHAR2(55) VARCHAR2(95) VARCHAR2(3000) VARCHAR2(55) NUMBER(5) NUMBER(10) VARCHAR2(25) VARCHAR2(5) VARCHAR2(25) VARCHAR2(55) REF_SUBJECT_LOOKUP REF_SUBJECT SHORT_DESCRIPTION LONG_DESCRIPTION VARCHAR2(12) VARCHAR2(40) VARCHAR2(150) REF_SUBJ REF_SUBJ ID REF_ID PV_ID DET_METHODID PROT_MUT_ ID INDUCING_MUTATIONID EXPRESSION_ID AFCS_RID ANTIBODY_ID MANIPULATIONID MRNA_ID REG_REGION_ID GENEID REF_SUBJECT CVL_MODIFICATION_ID CPD_MUTATION_ID KNOCK_ID TRANSGENICID CONCENTRATION_ID DISTRIBUTION_ID INTERACTIONID VARCHAR2(12) JOURNAL J_ABBREV JOURNAL PUBLISHER VARCHAR2(25) VARCHAR2(95) Dublin Core Ontology 20012002

65. Molecule Pages 2002

66. Molecule Page Interface and Demo Demo Molecule Pages 2002

67. Molecule Page Author Interface Author Interface The AfCS Bioinformatics Laboratory 2002

68. Clicking on any hyperlinked word within an individual record view searches all Mini Molecule Pages for that keyword. Mini Molecule Pages Record View 2002

69. RegisterLogin Create Browse Search Person Requested Molecules User Groups Protein List Mini Molecule Pages (Oracle) Edit Review Edit Approve Authentication And Access Control Overview of Mini Molecule Pages Database System 2002

70. A main source for protein functions and signaling protein interactions A signaling pathway database Virtual cell - modeling and simulation Other species 2001 Molecule Pages 2002

71. Querying AfCS Databases Roger Unwin DataScope 2002

72. Web Server Database (Oracle) CGI Scripts DataScope Custom Searches Images HTML Documents Site Hierarchy 2002

73. DataScope Actions User Actions Select Search What Happens During A Search Request Start Page Connect To DB Select Record to ViewSubmit Search Specs. Obtain List of Searches Beautify List Connect To DB Obtain Search Meta Code Generate SQL Run SQL Get Results Run Morph-Its Connect To DB Obtain Search Input Form Beautify Results Connect To DB Obtain Search Meta Code Generate SQL Run SQL Get Results Run Morph-Its Beautify Results The AfCS Bioinformatics Laboratory 2002

74. DataScope Sample Search 2002

75. DataScope Sample Search Results 2002

76. DataScope Sample Search Record 2002

77. Developer Start Screen 2002

78. Developer Search Configuration 2002

79. Developer Search Add Screen Item 2002

80. Developer Search Help Instructions Sample 2002

81. Developer Result Configuration 2002

82. Developer Record Configuration Sample 2002

83. Developer Record - Choose Pretty Printers 2002

84. The AfCS Data Coordination and Bioinformatics Laboratory 2002 “The” Goals Data Analysis in the Long Term Modeling Cellular Response to Input

85. Data Analysis 2002 Unsupervised Learning Supervised Learning Intermediate output Constraints Knowledge-based Constraints Hypothesis-driven Constraints

86. Data Analysis 2002 How do we decide whether two responses differ? Can we distinguish functionally distinct sets of ligands, each acting on a pathway? Can we identify functionally significant patterns of responses across many ligands? Can we more efficiently construct epistasis maps connecting signaling proteins in pathways?