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

2. BioSystems A Database of Biological Systems Materials prepared by: Cynthia Perreault-Micale, Ph.D. www.openhelix.com Updated: Q5 2011 Version 2.0

3. Copyright OpenHelix. No use or reproduction without express written consent3 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

4. Copyright OpenHelix. No use or reproduction without express written consent4 What is a BioSystem? A group of molecules that interact in a Biological System A pathway with interacting genes, proteins and small molecules A disease with interacting genes, biomarkers and drugs

5. Copyright OpenHelix. No use or reproduction without express written consent5 Many Biological Systems & Many Components Cardiac Muscle Contraction bsid 93992 A Conserved Biosystem 2 Major Record Types: Conserved & Organism- Specific Sequences, Structures, Taxonomy, and more Associated Proteins & Genes Small Molecules Related BioSystems: Organism-Specific, Linked & Similar Comments Literature - PubMed & OMIM

6. Copyright OpenHelix. No use or reproduction without express written consent6 Homepage Features & Links http://www.ncbi.nlm.nih.gov/biosystems/ Help & Contact Info Click here Search box Search hints & Entrez features Or here

7. Copyright OpenHelix. No use or reproduction without express written consent7 More About BioSystems Click to return to homepage Key links Pathway Sources: KEGG BioCyc Reactome PID

8. Copyright OpenHelix. No use or reproduction without express written consent8 Navigation & Support HOW TO: HELP: To homepage FTP site Next slide TOOLS: FAQ: NEWS: Statistics Sign up

9. Copyright OpenHelix. No use or reproduction without express written consent9 Credits to the Developers Cite BioSystems Next slide Cite sources Visit NCBI’s homepage http://www.ncbi.nlm.nih.gov

10. Copyright OpenHelix. No use or reproduction without express written consent10 BioSystems: Part of The NCBI Structure Group Cardiac Muscle Contraction bsid 93992 A Conserved Biosystem

11. Copyright OpenHelix. No use or reproduction without express written consent11 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

12. mTOR Copyright OpenHelix. No use or reproduction without express written consent12 Basic Search From NCBI Homepage http://www.ncbi.nlm.nih.gov Click Search Enter search term Our search example: mTOR

13. Copyright OpenHelix. No use or reproduction without express written consent13 Entrez Global Query - A Navigation Tool One query Many results BioSystems Click to reach results Click for description

14. http://www.ncbi.nlm.nih.gov Copyright OpenHelix. No use or reproduction without express written consent14 Additional Entry Points Enter search term & click “Search” to go to BioSystems results page Or just click “Search” to go to BioSystems homepage

15. Copyright OpenHelix. No use or reproduction without express written consent15 Basic Searches From BioSystems Homepage http://www.ncbi.nlm.nih.gov/biosystems/ Focus of upcoming tutorial sections Start here Enter term Click mTOR

16. Copyright OpenHelix. No use or reproduction without express written consent16 Basic Search Results Entrez functions: focus of “Entrez Review” section ID, Title, Type, Description, Organism & Source Click ID or title to view record rat mouse links

17. Copyright OpenHelix. No use or reproduction without express written consent17 Basic Search Results - Right Side Options Recent Activity Selected BioSystems View links in database View subset of results with links View list ranked in FLink Related data links for a specific record Toggle groups open or closed Additional Links to related data

18. Copyright OpenHelix. No use or reproduction without express written consent18 Links to Related Data - BioSystems & Literature Help OMIM may be found in this group of links May also find Organism-Specific, Superset & Subset BioSystems here

19. Copyright OpenHelix. No use or reproduction without express written consent19 Links to Related Data - Sequences ProteinClusters may be found in this group More than 800!

20. Copyright OpenHelix. No use or reproduction without express written consent20 Links to Related Data - Small Molecules

21. Copyright OpenHelix. No use or reproduction without express written consent21 Links to Related Data - Other Links Structures may be found in this group of links

22. Copyright OpenHelix. No use or reproduction without express written consent22 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

23. Copyright OpenHelix. No use or reproduction without express written consent23Copyright OpenHelix. No use or reproduction without express written consent23 Entrez Review Biosystems includes the following functions that are described in detail in the OpenHelix tutorial: “Entrez Overview”: LIMITS: Exclude or include specific types of records: limit by database source, for example PREVIEW / INDEX: Select specific field, then enter term in query box to find indexed terms; add to search with AND, OR, or NOT CLIPBOARD: Allows you to store your records, after clicking the checkbox(es) on your results page, select “Clipboard” in the “Send to” pulldown menu HISTORY: Previously performed searches can be combined using AND, OR, and NOT, for example: #1 AND #2 (use the “#” symbol) DETAILS: Click tab to view details of how search was performed

24. Copyright OpenHelix. No use or reproduction without express written consent24Copyright OpenHelix. No use or reproduction without express written consent24 Entrez Review, Features Unique to BioSystems - 1 “Display”, “Show”, “Sort by” and “Send to” functions: Display your records in different ways, select specific links to view Sort records by modification dates “Send to” Text, File, Printer, Clipboard, or CSV (Comma Separated Value) file for saving, printing and storing Choose how many records per page using “Show”

25. Copyright OpenHelix. No use or reproduction without express written consent25 See Help for More Details - Access on Homepage Select “BioSystems Help” link on homepage

26. Copyright OpenHelix. No use or reproduction without express written consent26Copyright OpenHelix. No use or reproduction without express written consent26 Entrez Review, Features Unique to BioSystems - 2 Filters, “My NCBI”, Symbols and Links: Filter tabs: View “All” results and subsets, defaults are Conserved BioSystems and Organism Specific BioSystems Mouse over symbols for explanations Links to Related BioSystems, Literature, Sequences, Small Molecules, Other. Click for pop up menu, choices vary “My NCBI” to customize searches, select filters, choose search terms, receive regular updates, save search

27. Copyright OpenHelix. No use or reproduction without express written consent27 Entrez Review, My NCBI Easy access Learn more Access Edit Explore other options

28. Copyright OpenHelix. No use or reproduction without express written consent28 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

29. Copyright OpenHelix. No use or reproduction without express written consent29 Accessing BioSystems Records Click ID or title to access record Or enter bsid 84109 & click “Go” Record types

30. Copyright OpenHelix. No use or reproduction without express written consent30 Records Lower: folders of genes, proteins, small molecules, related BioSystems, citations, comments Upper: title, ID, type, organism, source, thumbnail of pathway, links to the right Links we examined previously - remember they have dropdown menus also Download ASN.1, XML, JSON

31. Copyright OpenHelix. No use or reproduction without express written consent31 Record Features -Top Section: Taxonomy & Source

32. Copyright OpenHelix. No use or reproduction without express written consent32 Record Features -Top Section: Help & Full Image Click question mark to go to relevant Help section Click here, or on thumbnail, to link to full size source image

33. Copyright OpenHelix. No use or reproduction without express written consent33 Full Size Image of mTOR Signaling Pathway http://www.genome.jp/kegg/ Source features to customize results

34. Copyright OpenHelix. No use or reproduction without express written consent34 Folders Folders of Data

35. Copyright OpenHelix. No use or reproduction without express written consent35 Folders of Components - Associated Genes To Help Folders contain categorized lists of biosystem components & associated data These complement the links to related data menus Many pages of data Link to Entrez Gene Check records & view, save, clear or highlight

36. Copyright OpenHelix. No use or reproduction without express written consent36 Highlighted Pathway Components

37. Copyright OpenHelix. No use or reproduction without express written consent37 Folders of Components - Associated Proteins Protein Identity Group, PIG: same sequence (length & composition) regardless of taxonomy ID Select filter to view all protein sequence records, or subsets like Non-Redundant or Swiss-Prot/UniProt To Entrez Protein Sorting by PIG ID Only Swiss-Prot/UniProt Default; only one representative protein record per PIG All protein sequence records associated with biosystem Similar options

38. Copyright OpenHelix. No use or reproduction without express written consent38 Folders of Components - Small Molecules Associated PubChem Substances & Compounds ↔

39. Copyright OpenHelix. No use or reproduction without express written consent39 Folders of Components - Related BioSystems Includes Conserved, Linked & Similar BioSystems Links are to respective BioSystems records Similar BioSystems: protein with same PIG & TaxID

40. Copyright OpenHelix. No use or reproduction without express written consent40 Folders of Components - Citations & Comments PubMed records whose PMID was cited in source Light gray tab indicates no associated comments Link to PubMed

41. Copyright OpenHelix. No use or reproduction without express written consent41 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

42. http://www.ncbi.nlm.nih.gov/biosystems/ Copyright OpenHelix. No use or reproduction without express written consent42 Many Types of Advanced Searches Advanced methods here Help Table of Contents: BioSystems & Entrez Help

43. Copyright OpenHelix. No use or reproduction without express written consent43 Limiting Your Searches More hints & help Our initial query BioSystem Type

44. Copyright OpenHelix. No use or reproduction without express written consent44 Limited Search Results Remember to uncheck the limits box Use the Details tab to check query Read translated query to learn about complex Boolean queries

45. Copyright OpenHelix. No use or reproduction without express written consent45 Complex Boolean Queries You could do the same search by learning some basic syntax The Details tab translated query Field qualifiers in brackets Terms nested with parentheses The default field qualifier is “All Fields” BioSystems Help lists field qualifiers A complex Boolean query = combine field qualifiers, nest with parentheses, group with quotes, use Boolean operators

46. Copyright OpenHelix. No use or reproduction without express written consent46 Preview/Index Functions Choose Field Click Index Select term Pick Boolean Previous Limits Click to select

47. Copyright OpenHelix. No use or reproduction without express written consent47 Results If only one match to your query then you will be taken directly to the record

48. Copyright OpenHelix. No use or reproduction without express written consent48 History & Clipboard Functions Combine searches by entering their numbers and a Boolean into search box, i.e., #2 AND #7 Save searches in Clipboard temporarily or in “My NCBI” indefinitely

49. Copyright OpenHelix. No use or reproduction without express written consent49 Additional Tools Available Click “TOOLS” on homepage navigation bar to access Click

50. Copyright OpenHelix. No use or reproduction without express written consent50 FLink – Quick Start Guide Sample input file Three easy steps: 1.Input ID list from one database 2.Review and select “destination” database 3.Output ranked list of “destination” hits Note: invalid IDs cause tool error, therefore Batch Entrez check advisable (see help) http:// www.ncbi.nlm.nih.gov/sites/batchentrez

51. Data not yet available for FLink analysis Copyright OpenHelix. No use or reproduction without express written consent51 FLink - Frequency Weighted Links http:// www.ncbi.nlm.nih.gov/sites/batchentrez Databases FLink logos CDD record associated with 229 mTOR hits Frequency weight indicates relevance

52. Click here Copyright OpenHelix. No use or reproduction without express written consent52 FLink Example http://www.ncbi.nlm.nih.gov/Structure/flink/flink.cgi

53. Copyright OpenHelix. No use or reproduction without express written consent53 FLink Results Ranked by Frequency Many pages

54. Copyright OpenHelix. No use or reproduction without express written consent54 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

55. http://www.ncbi.nlm.nih.gov/biosystems/ Copyright OpenHelix. No use or reproduction without express written consent55 BioSystems: A Database of Biological Systems Handy Entrez Tools Many Search Methods: Basic, Advanced, Boolean, Batch

56. Copyright OpenHelix. No use or reproduction without express written consent56 Detailed Folders of Associated Components

57. Copyright OpenHelix. No use or reproduction without express written consent57 Options to Customize Results Highlight pathway components you are interested in!

58. Copyright OpenHelix. No use or reproduction without express written consent58 BioSystems Agenda Introduction and Credits Basic Searches Entrez Review Record Features Advanced Searches Summary Exercises BioSystems: http://www.ncbi.nlm.nih.gov/biosystems/

59. Copyright OpenHelix. No use or reproduction without express written consent59