Structured gene annotations are a foundation on which many bioinformatics and statistical analyses are built, however their representation is quite sparse – in comparison to the total knowledge that could be captured. As centralized biocuration efforts struggle to keep up with the rate of biomedical data generation, new models for gene annotation need to be explored. Recently, online games have emerged as an effective way to recruit, engage and organize contributors to help address difficult challenges like online image tagging (ESP Game), protein folding (Foldit), or multiple sequence alignment (Phylo). We present here two online games - Dizeez and GenESP - aimed at identifying novel gene-disease annotations, i.e. gene-disease links well established in the literature, but not yet reflected as structured annotations. Preliminary results are provided from game play online and at scientific confer-ences. These data suggest that even after limited game play, novel gene-disease annotations can be mined from game playing logs. Both games are available at http://genegames.org.

1. Games)for)Human)Gene)AnnotaDon)
Salvatore)Loguercio*,)Benjamin)Good,)Andrew)Su)
Department)of)Molecular)and)Experimental)Medicine)
The)Scripps)Research)InsDtute)
ISMB)
BioEOntologies)SIG)
July)13,)2012)

2. 2
Growth of potential annotations
1000000 PubMed in 2012:
950000 > 21 million articles.
900000
Approaching 1 million
850000 new articles per year
Number of
800000 (>1/minute)
articles
added to 750000
PubMed 700000
650000
600000
550000
500000

3. 3
Number of articlesof humantypical scientist
Average capacity read by scientist
20
10
0
1979 1984 1989 1994 1999 2004 2009

4. GO)
1.5%)of)PubMed*)cited) PubMed)
by)GO)annotaDons)
*311,696)arDcles)(2011)))

5. 5
Sooner or later, the
research community will
need to be involved in the
0
annotation effort to scale
up to the rate of data
generation.

6. How)to)involve)the)community)
in)gene)annotaDon?)

7. Crowdsourcing)Biology)

8. Gene)Wiki:)
Comprehensively)organize)
knowledge)of)all)human)genes)

9. Gene)annotaDon)portal)for)
aggregaDng)geneEcentric)
online)content)
h]p://biogps.org))

10. Biological)games)
Build)scienDfic)knowledge)
through)game)play)

11. Why)games?)

12. It)is)esDmated)that)9)billion)
hours)are)spent)playing)
Solitaire)every)year)

13. 13)
Seven million human hours
h]p://www.flickr.com/photos/archana3k1/4124330493/)

14. 14)
Twenty million human hours
h]p://www.flickr.com/photos/ableman/2171326385/)

15. 15)
150 billion human hours E)
per year
h]p://www.flickr.com/photos/rvpEcw/6243289302/)

16. Can)we)harness)some)of)this)
Dme)and)energy?))

17. Games)with)a)purpose)

18. Label)all)images)on)the)Web)
Devise)protein)folding)algorithms)
Fix)mulDple)sequence)alignments)
Design)RNA)molecules)

19. Annotate)all)human)genes)

20. Record)the)relevant)properDes)of)each)gene)in)a)manner)that)
facilitates)computaDon)
• biological)process)
• molecular)funcDon)
• cellular)localizaDon)
• interacDon)partners)
• disease)relevance)
Gene) • genomic)locaDon)
• geneDc)variaDons)
• post)translaDonal)
modificaDons)
• related)drugs)
• related)publicaDons)
• ...)

21. Dizeez:)geneEdisease)associaDon)quiz)

22. DIZEEZ:)geneEdisease)associaDon)quiz)
hurry!
then on to the next question
If its ‘right’, you get points
Click the related disease
h]p://genegames.org)

23. Gameplay)
• AdverDsed)with)a)blog)post,)a)few)tweets)and)conference)poster)
• Results)since)Dec.)2011:)
– 180)people)have)played)it)
– 713)one)minute)game)rounds)have)been)completed)
– 5,282)disDnct)geneEdisease)associaDons)collected)

24. Quality)through)replicaDon)
DisDnct)geneEdisease)pairs)collected) 5,282)
482)) collected)more)than)once)
PotenDal)new)annotaDons)
(do)not)appear)in)OMIM,)PharmGKB))
223))
example:)ABCB5))Acute)myeloid)leukemia))

25. Novel)annotaDons)E)I)
#&Occurrences& Gene& Disease& Pubmed) OMIM) PharmGKB) Gene&Wiki)
7) GAST% gastrinoma)
7) RBP3% reDnoblastoma)
7) SSX1% synovial)sarcoma)
6) TG% Graves')disease)
6) CRYGC%% Cataract)
6) SOX8% mental)retardaDon)
6) WRN%% Werner)syndrome)
6) ABL1%% leukemia)
6) MLL3%% leukemia)
6) SNAI2%% breast)carcinoma)
2010)or)later)

26. Novel)annotaDons)E)II)
#&Occurrences& Gene& Disease& Pubmed) OMIM) PharmGKB) Gene&Wiki)
2) ABCB5) acute)myeloid)leukemia)
2) HOXB7) leukemia)
2) SULF1) carcinoma)
2) ALPP) reDnoblastoma)
2) FOXM1) Melanoma)
2009)or)later)

27. Current)limitaDons))
• Dizeez)actually)punishes)desired)behavior)(adding)new,)unknown)
associaDons))by)not)awarding)points)
• Does)not)allow)player)to)enter)associaDons)other)than)those)in)
the)provided)list)
• GenESP)fixes)both)problems)

28. GenESP:)gene)E)concept)associaDon)with)a)partner)

29. Gene)–)concept)associaDon)with)a)partner)
(modeled)amer)the)ESP)Game).)See:)Ahn)and)Dabbish)(2004))Labeling)images)with)a)computer)game,)SIGCHI)
h]p://genegames.org)

30. A)reEusable)pa]ern)
Gene) Disease)
Gene) FuncDon)
Gene) Gene)
Gene) relaDonship) Gene)
The Gene Wiki Hairball!

31. )Geong)players))

32. MulDplayer)Online)E)“Farmville) Social)gaming)
for)gene)annotaDon”)
EducaDng)players) Arena)mode)
Building)a)community)) labs)vs.)labs)
Dizeez&
TP53!)
SOX2!)

34. Epilogue)
Crowdsourcing)for)knowledge)acquisiDon)

35. TradiDonal)model) Crowdsourced)model)
Knowledge) Knowledge)
Small)expert)
group) Data) Data)and)contributors)

36. TradiDonal)model) Crowdsourced)model)
ComputaDon)

37. Annotate)all)human)genes)

38. Special)thanks)to:) Su)Lab)@)TSRI)
Erik)Clarke) Ian)Macleod)
Ben)Good) Max)Nanis) Chunlei)Wu)
Andrew)Su)
Crowdsourcing)Biology)@)GSoC)2012!)
Students:)
Clarence)Leung) Interwebs&
Carolina)Lidstrom) h]p://sulab.org)
loguerci@scripps.edu)
@sal999)
+Salvatore)Loguercio)
Funding&and&Support&
(BioGPS:)GM83924,)Gene)Wiki:)GM089820))