1. SRI International Bioinformatics 1 SmartTables & Enrichment Analysis Peter Karp SRI Bioinformatics Research Group September 2015

2. SRI International Bioinformatics 2 SmartTables (formerly Web Groups) Collect lists of database objects Genes, metabolites, pathways, sequence regions, … Transform them into related objects (eg: transform list of genes → list of pathways) Filter and combine Share with public or specific collaborators, publish Export to spreadsheet Omics analyses

3. SRI International Bioinformatics 3 SmartTables Location BioCyc.org, HumanCyc.org, EcoCyc.org… To create saved SmartTables, create a (free) BioCyc account for yourself From the web menu: SmartTables->My SmartTables

4. SRI International Bioinformatics 4 Three Types of SmartTables Created by you Public Special Most SmartTables associated with a single PGDB

5. SRI International Bioinformatics 5 Creating SmartTables: User-Defined SmartTables Create a SmartTable Type in metabolite names From search results Upload a tab- delimited text file

6. 6 SRI International Bioinformatics Creating SmartTables: User-Defined SmartTables Create a SmartTable by typing in names Operations -> New -> SmartTable of Objects from Text Entry Names will be converted to rows of objects

7. 7 SRI International Bioinformatics Creating SmartTables from Search Results Turn into a SmartTable button appears on all search results

8. 8 SRI International Bioinformatics Using SmartTables: Browsing Attributes

9. 9 SRI International Bioinformatics SmartTable Columns Object ID Sort Hide Set display mode First column: object ID vs common-name Sequences Delete

10. 10 SRI International Bioinformatics SmartTable Transformations Create new columns that are computed from existing columns Those columns can be converted to new SmartTables via "+"

11. 11 SRI International Bioinformatics Using SmartTables: SmartTable Transformations Use Case: Find all genes that are regulated by a transcriptional regulator. Step 1: Create a SmartTable that contains the transcription factor. Step 2: In the “Transforms” menu, select “Regulation – genes regulated by polypeptide, complex, or RNA”. A new column containing all genes regulated by the transcription factor is generated. This SmartTable can be further transformed, e.g. into metabolic pathways. The resulting lists can be exported.

12. 12 SRI International Bioinformatics Using SmartTables: Attributes Use Case: Find the chromosome positions of all genes encoding enzymes of a pathway, sort by position. Find regulators of those genes. Step 1: Create a group that contains the pathway. Step 2: In the “Transforms” menu, select “Genes of pathway”. Step 3: Select gene column and select Operations > New > Group from column OR Click “+” at top of gene column Step 4: Select “left-end-position” from “Add Property Column” menu and add. Sort by position by clicking on arrow in column header. Step 5: Select “Direct regulators of gene” from “Add Transform Column” menu.

13. 13 SRI International Bioinformatics Genes of Aspartate Superpathway

14. 14 SRI International Bioinformatics Transforms

15. 15 SRI International Bioinformatics Other Operations on SmartTables Set union, intersection, difference among two SmartTables Filter SmartTable rows to keep/reject all rows containing specified value or substring or regular expression Share SmartTable with public or specified users Freeze SmartTable for publication

16. 16 SRI International Bioinformatics Genes, Sequences, Regions….

17. 17 SRI International Bioinformatics Set Operations on SmartTables

18. 18 SRI International Bioinformatics Alignment Viewer

19. 19 SRI International Bioinformatics Frozen SmartTables

20. 20 SRI International Bioinformatics Collapsible Columns, Select Rows By Number

21. 21 SRI International Bioinformatics Enrichment Analysis * Statistical method to find classes of objects that have more or less objects than would be expected by chance * Based on the Hypergeometric Distribution * Can perform enrichment, depletion, or both * Multiple ontologies can be used in Pathway Tools * Multiple testing correction optional

22. 22 SRI International Bioinformatics Enrichment Dialog

23. 23 SRI International Bioinformatics Lab Exercise 1.Search for compounds that have 'glucose' in their name 2.Turn into SmartTable 3.Enrichment Analysis → Compounds Enriched for Pathways 4.Use defaults in Enrichment pop-up, click 'OK’ 5.Select ten most enriched pathways 6.Operations → New → From checked rows 7.Reactions of pathway 8.New SmartTable of reactions (green button on column) 9.Operations → Paint Data → On cellular overview

24. 24 SRI International Bioinformatics Lab Exercise 1.Create a SmartTable containing all E. coli enzymes with a molecular weight greater than 500; determine the map positions of the genes encoding those enzymes 2.Determine which enzymes in E. coli are heteromultimers 3. Create a SmartTable of metabolites and determine what metabolic pathways those metabolites are involved in 4.Export a SmartTable to a file 5.Share a SmartTable with the person next to you