Yale Pseudogene Analysis as part of GENCODE Project Sanger Center 2009.01.20, 11:20-11:40 Date Given: 01/21/2009

1. Yale Pseudogene Analysis as part of GENCODE Project Sanger Center 2009.01.20, 11:20-11:40 Mark B Gerstein Yale (c) Mark Gerstein, 2002, Yale, bioinfo.mbb.yale.edu Illustration from Gerstein & Zheng (2006). Sci Am.

4. Additional Annotation on Pseudogenes: Consistent Labeling (Ontology)

5. Gene duplicated_from mutated_from retrotranscribed_from Protein family contained_in has_pseudogene_family mRNA Protein transcribed_into translated_into Pseudogene family type_of Sequence Region Segmental Duplication Syntenic Region etc is_a contained_in contained_in has_parent_protein derives_from Domain Ontology Pseudogene Upper Ontology [Lam et al., NAR DB Issue (in press, '09)] Pseudogene Duplicated Unitary Transcribed Regulatory Processed … …

6. Pseudogene Duplicated Unitary Transcribed Regulatory Processed Classified Type Semi Processed Duplicated Processed Polymorphic Feature Evidence Sequence Homology Intra-Genome Homology Cross-Genome Homology Recognition Feature Disablement Premature Stop Codon Regulatory Element Lost Frameshift Pseudo-PolyA Tail Nucleus Mitochondria Origin has a is a Domain Ontology *Unprocessed Proposed HAVANA [Lam et al., NAR DB Issue (in press, '09)]

7. Collections to provide further annotation OTTHUMG00000000445 HAVANA ENSP00000384933.frag.301873 BC067222.1-28 urn:lsid:pseudogene.org:9606.Pseudogene:27570 urn:lsid:pseudogene.org:9606.Pseudogene:27579 urn:lsid:pseudogene.org:9606.Pseudogene:29 Human Pseudogenes Yale UCSC Ribosomal Protein Transcribed

8. Additional Annotation on Pseudogenes: Families & Histories

12. Pseudofam Statistics: Enrichment of pseudogenes within a family ("Living vs Dead") Total (10 Eukaryotes) Human [Lam et al., NAR DB Issue (in press, '09)]

13. Pseudogene Set #2: RP pseudogenes

14. Human Ribosomal Proteins (RP) [Zhang et al . Genome Research , 2002] 79 Functional RP genes Nakao A, Yoshihama M, Kenmochi N: RPG: the Ribosomal Protein Gene database. Nucleic Acids Res 2004, 32:D168-170.

15. Human Ribosomal Proteins (RP) ~ 2000 RP  genes [Zhang et al . Genome Research , 2002] 79 Functional RP genes

16. Number of RP pseudogenes (identified by pipeline) RP pseudogenes constitute the largest family of pseudogenes. Almost all are processed: There are ~90 clearly duplicated ones in the human genome [Balasubramanian et al., Genome Biol. ('09)] Organism Processed Fragments Low confidence Human 1822 218 212 Chimp 1462 219 160 Mouse 2092 326 413 Rat 2848 343 450

17. Number of each type of human ribosomal protein processed pseudogenes appears unrelated to expression level or to number in mouse [Balasubramanian et al., Genome Biol. ('09)]

18. Using Synteny to Improve Annotation of RP pgenes Synteny derived based on local gene orthology [Balasubramanian et al., Genome Biol. ('09)]

19. Syntenic proc pseudogenes [Balasubramanian et al., Genome Biol. ('09)] Species1- Species2 Number of syntenic pgenes Human-chimp 1282 Human-mouse 6 Human-rat 11 Rat-mouse 394

20. A human-mouse syntenic pgene, likely to be coding [Balasubramanian et al., Genome Biol. ('09)] Nakao A, Yoshihama M, Kenmochi N: RPG: the Ribosomal Protein Gene database. Nucleic Acids Res 2004, 32:D168-170.

21. Set #3: Transcribed Pseudogenes Annotated Earlier

23. Set #4: Strong Consensus Pseudogenes

29. High Quality Overlaps?

32. Set #5: SD pseudogenes

37. Extra

39. Pseudofam & Pseudogene.org Integration PseudoPipe svn annotations via shared ID

40. gencode.gersteinlab.org/consensus