1. Tools in Bioinformatics Genome Browsers

2. Retrieving genomic information Previous lesson(s): annotation-based perspective of search/data Today: genomic-based perspective: look at all the data from the prism of a specific chromosome location Next: sequence-based searches

3. Genome browsers NCBI Map Viewer http://www.ncbi.nih.gov/mapview Ensembl http://www.ensembl.org/ UCSC Genome Browser http://genome.ucsc.edu/

4. Copyright OpenHelix. No use or reproduction without express written consent4

5. 5 Important note to slide users: To maintain the color schemes/cues and the animations, if you import these slides into other slide sets please click the checkbox in the PowerPoint Insert window that maintains slide format. Otherwise important information may be lost. Mac usersPC users

6. Version16a_0209 Copyright OpenHelix. No use or reproduction without express written consent 6 The UCSC Genome Browser Introduction Materials prepared by Mary Mangan, Ph.D. www.openhelix.com Updated: Q1 2009

7. Copyright OpenHelix. No use or reproduction without express written consent7 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises Introduction and Credits

8. Copyright OpenHelix. No use or reproduction without express written consent8 Organization of Genomic Data Genome backbone: base position number sequence Annotation Tracks chromosome band known genes predicted genes evolutionary conservation SNPs sts sites gap locations repeated regions microarray/expression data more… Links out to more data

9. Copyright OpenHelix. No use or reproduction without express written consent9 A Sample of the UCSC Genome Browser gene details Annotation Tracks official sequence comparisons SNPs

10. Copyright OpenHelix. No use or reproduction without express written consent10 UCSC Genome Browser Credits Led by David Haussler and Jim Kent Dozens of staff and students bring you this software and data Development team: http://genome.ucsc.edu/staff.html http://genome.ucsc.edu/goldenPath/credits.html Funding, data sources, external contributors

11. Copyright OpenHelix. No use or reproduction without express written consent11 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

12. Copyright OpenHelix. No use or reproduction without express written consent12 The UCSC Homepage: http://genome.ucsc.edu navigate General information Specific information— new features, current status, etc.

13. Copyright OpenHelix. No use or reproduction without express written consent13 Genome Browser Gateway: start page, basic search text/ID searches Helpful search examples samples provided Use this Gateway to search by: Gene names, symbols, IDs Chromosome number: chr7, or region: chr11:1038475-1075482 Keywords: kinase, receptor See lower part of page for help with format

14. Copyright OpenHelix. No use or reproduction without express written consent14 The Genome Browser Gateway Make your Gateway choices: 1. Select Clade 2. Select genome = species: search 1 species at a time 3. Assembly: the official backbone DNA sequence 4. Position: location in the genome to examine 5. Image width: how many pixels in display window; 5000 max 6. Configure: make fonts bigger + other choices 45 1 3 2 assembly 6

15. Copyright OpenHelix. No use or reproduction without express written consent15 The Genome Browser Gateway sample search for Human TP53 Sample search: human, March 2006 assembly, tp53 select Select from results list ID search may go right to a viewer page, if unique

16. Copyright OpenHelix. No use or reproduction without express written consent16 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

17. Copyright OpenHelix. No use or reproduction without express written consent17 Overview of the Whole Genome Browser Page (mature release) } Genome viewer section mRNA and EST Tracks Expression (such as microarray) Comparative Genomics As a group Individual species Variation and Repeats (including SNPs, copy number variation) Groups of data (Tracks) Mapping and Sequencing Tracks Genes and Gene Prediction Tracks (including sno/miRNA data) ENCODE Tracks Phenotype and Disease Tracks Regulation (including TFBS)

18. Copyright OpenHelix. No use or reproduction without express written consent18 Different Species, Different Tracks, Same Software Species may have different data tracks Layout, software, functions the same

19. Copyright OpenHelix. No use or reproduction without express written consent19 Sample Genome Viewer Image, TP53 Region base position UCSC genes RefSeq genes mRNAs & ESTs repeats many species compared SNPs single species compared MGC clones

20. Copyright OpenHelix. No use or reproduction without express written consent20 Visual Cues on the Genome Browser Track colors may have meaning—for example, UCSC Gene track: If there is a corresponding PDB entry = black If there is a corresponding reviewed/validated seq = dark blue If there is a non-RefSeq seq = lightest blue Tick marks; a single location (STS, SNP) For some tracks, the height of a bar is increased likelihood of an evolutionary relationship (conservation track) Intron and direction of transcription >> < exon < < << < ex 5' UTR3' UTR Alignment indications (Conservation pairs: “chain” or “net” style) Alignments = boxes, Gaps = lines

21. Copyright OpenHelix. No use or reproduction without express written consent21 Options for Changing Images: Upper Section Change your view or location with controls at the top Use “base” to get right down to the nucleotides Configure: to change font, window size, more… Next item, next exon navigation assistance can be turned on Specify a position Fonts, window, next item, more Walk left or right Zoom in Zoom out Click to zoom 3x and re-center

22. Copyright OpenHelix. No use or reproduction without express written consent22 Annotation Track Display Options Some data is ON or OFF by default Menu links to info about the tracks: content, methods You change the view with pulldown menus After making changes, REFRESH to enforce the change enforce changes Enforce changes Change track view Links to info and/or filters

23. Copyright OpenHelix. No use or reproduction without express written consent23 Annotation Track Options Defined Hide: removes a track from view Dense: all items collapsed into a single line Squish: each item = separate line, but 50% height + packed Pack: each item separate, but efficiently stacked (full height) Full: each item on separate line

24. Copyright OpenHelix. No use or reproduction without express written consent24 Mid-page Options to Change Settings You control the views Use pulldown menus Configure options page Reset, back to defaults Start from scratch Enforce any changes (hide, full, squish…) Flip display to Genomic 3’  5’

25. Copyright OpenHelix. No use or reproduction without express written consent25 Cookies and Sessions Your browser remembers where you were (cookies) To clear your “cart” or parameters, click default tracks or reset OR Save your setup as “sessions” and store/share them

26. Copyright OpenHelix. No use or reproduction without express written consent26 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

27. Copyright OpenHelix. No use or reproduction without express written consent27 Click Any Viewer Object for Details Example: click your mouse anywhere on the TP53 line Click the item New description web page opens Many details and links to more data about TP53

28. Copyright OpenHelix. No use or reproduction without express written consent28 Click Annotation Track Item for Details Pages Not all genes have this much detail. Different annotation tracks carry different data. informative description other resource links microarray data mRNA secondary structure links to sequences protein domains/structure orthologs in other species Gene Ontology™ descriptions mRNA descriptions pathways genetic association studies comparative toxicology gene model

29. Copyright OpenHelix. No use or reproduction without express written consent29 Get DNA, with Extended Case/Color Options Use the DNA link at the top Plain or Extended options Change colors, fonts, etc.

30. Copyright OpenHelix. No use or reproduction without express written consent30 Get Sequence from Details Pages Click a track, go to Sequence section of details page Click the item sequence section on detail page

31. Copyright OpenHelix. No use or reproduction without express written consent31 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

32. Copyright OpenHelix. No use or reproduction without express written consent32 Accessing the BLAT Tool Rapid searches by INDEXING the entire genome Works best with high similarity matches See documentation and publication for details Kent, WJ. Genome Res. 2002. 12:656 BLAT = BLAST-like Alignment Tool

33. Copyright OpenHelix. No use or reproduction without express written consent33 BLAT Tool Overview: www.openhelix.com/sampleseqs.html Make choices DNA limit 25000 bases Protein limit 10000 aa 25 total sequences Paste one or more sequences Or upload submit

34. Copyright OpenHelix. No use or reproduction without express written consent34 BLAT Results with Hyperlinks Results with demo sequences, settings default; sort = Query, Score Score is a count of matches—higher number, better match Click browser to go to Genome Browser image location (next slide) Click details to see the alignment to genomic sequence (2 nd slide) sorting go to browser/viewergo to alignment detail

35. Copyright OpenHelix. No use or reproduction without express written consent35 BLAT Results: Browser From browser click in BLAT results A new line with Your Sequence from BLAT Search appears! Base position = “full” menu and zoomed in enough to see amino acids in 3 frame translation query

36. Copyright OpenHelix. No use or reproduction without express written consent36 BLAT Results, Alignment Details Your query Genomic match, color cues Side by Side Alignment yours genomic

37. Copyright OpenHelix. No use or reproduction without express written consent37 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

38. Copyright OpenHelix. No use or reproduction without express written consent38 Introduction Summary UCSC Genome Browser Visual cues and genomic context Many ways to alter your views Access to deeper data Access and use sequence data

39. Copyright OpenHelix. No use or reproduction without express written consent39 UCSC Genome Browser Agenda UCSC Genome Browser: http://genome.ucsc.edu Introduction and Credits Basic Searches Understanding Displays Get Details or Sequences Sequence Searches (BLAT) Summary Exercises

40. Copyright OpenHelix. No use or reproduction without express written consent40 Hands-on Session for Introduction Exercises provided as document We will walk through them together 2 styles: questions only, and step-by-step When we are finished the formal exercises, we can help you to investigate issues that you want to understand for your research

41. Copyright OpenHelix. No use or reproduction without express written consent41 Notice: The materials and slides offered are for non-commercial use only. Reproduction, distribution and/or use for commercial purposes is strictly prohibited. Copyright 2009, OpenHelix, LLC http://www.openhelix.com/ucsc