Gene annotation games

GAMES FOR HUMAN GENE ANNOTATION Benjamin Good*, Salvatore Loguercio, Andrew Su The Scripps Research Institute http://genegames.org April 20, 2012 7 th Annual Systems to Synthesis Symposium at the Salk Institute

WHY GAMES? It is estimated that 9 billion hours are spent playing Solitaire every yearVon Ahn L. : Google Tech Talk: Human Computation 2006.

Seven million hours of human labor ONE YEAR SOLITAIRE = 1,285 EMPIRE STATE BUILDINGS Empire State BuildingVon Ahn L. : Google Tech Talk: Human Computation 2006.

150 billion hours 1.6E+11 1.4E+11 1.2E+11 1E+11 8E+10 6E+10 4E+10 2E+10 0 empire state one year of one year of building solitaire games 7M 9B 150BMcGonigal J. Reality is broken : why games make us better and how they can change the world.New York: Penguin Press; 2011.

GAMES WITH A PURPOSELabel all images on the Web Devise protein folding algorithms Fix multiple sequence alignments Design RNA molecules

Annotate all human genes

ANNOTATE ALL HUMAN GENESRecord the relevant properties of each gene in a manner that facilitates computation • biological process • molecular function • cellular localization • interaction partners • disease relevance Gene • genomic location • genetic variations • post translational modifications • related drugs • related publications • ...

BUILDING AN ANNOTATION 1. do science 2. publish it 3. curate the knowledge Gene Biological process, disease etc.image credits:phillipmartin.infowikipedia.org/wiki/Manuscriptbeyondcomputingmag.com/

WHY DOES HE LOOK SO TIRED?

MANY SCIENTISTS, POWERFUL TOOLS

GROWTH OF POTENTIAL ANNOTATIONS 1000000 950000 900000 112 publications/hour 850000 (37 more by the end of this talk) Number 800000 articles 750000 added to PubMed 700000 650000 600000 550000 500000

HOW DO WE INVOLVE THE COMMUNITY IN GENEANNOTATION?

HOW DO WE INVOLVE THE COMMUNITY IN GENEANNOTATION? Make it fun!

LINK GENES TO DISEASES WITH DIZEEZ hurry! then on to the next question If its ‘right’, you get points Click the related disease

DIZEEZ IS FUN.. TO SOME PEOPLE• Advertised 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 • 4,585 distinct gene-disease associations collected

QUALITY THROUGH REPLICATION Distinct gene-disease pairs collected 4,585 482 collected more than once Potential new annotations (do not appear in OMIM, PharmGKB 224 example: ABCB5  Acute myeloid leukemia

ABCB5 IS RELATED TO ACUTE MYELOID LEUKEMIA

PROBLEMS WITH DIZEEZ• Dizeez actually punishes desired behavior (adding new, unknown associations) by not awarding points• Does not allow player to enter associations other than those in the provided list• GenESP fixes both problems

(modeled after the ESP Game). See: Ahn and Dabbish (2004) Labeling images with a computer game, SIGCHI

NO DATA YET, PLAY NOW!http://genegames.org

A RE-USABLE PATTERN Gene Disease Gene Function Gene Gene Gene relationship Gene

GENOMIC PREDICTORScancer normal make predictions on new samples find patterns cancer normal

THE TRICK IS TO FIND THE RIGHT COMBINATION Out of the 25,000+ genes, which work together the best? Purely computational approaches have they always find patterns, hard to trouble generalizing know when they are real

NETWORK GUIDED FOREST (NGF) Use network to find good gene combinationsDutkowski & Ideker (2011) Protein Networks as Logic Functions in Development in Development and Cancer. PLoS Computational Biology

THE TRICK IS TO FIND THE RIGHT COMBINATION

‘COMBO’: FIND THE RIGHT COMBINATION OFGENES TO BUILD A PHENOTYPE PREDICTOR

HUMAN GUIDED FOREST (HGF) Let COMBO players build decision moduleshttp://i9606.blogspot.com/2012/04/human-guided-forests-hgf.html

150 billion hours... 1.6E+11 1.4E+11 1.2E+11 1E+11 8E+10 6E+10 4E+10 2E+10 0 empire state one year of one year of building solitaire games 7M 9B 150BMcGonigal J. Reality is broken : why games make us better and how they can change the world.New York: Penguin Press; 2011.

THE ENDThanks to: More information at: http://genegames.orgAndrew SuSalvatore Loguercio http://sulab.org/ bgood@scripps.edu our poster!

GO IS NOT KEEPING UP 1200000 1000000 112 publications/hour (37 more by the end of this talk) 800000 >21 million 600000 articles indexed in pubmed total GO annotations created 400000 200000 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

ANOTHER MAJOR ANNOTATION PROBLEMAnnotate all the images on the web dog firehose drinking sprinkler

A SUCCESSFUL MODEL

ESP GAME RESULTSfirst 3 months (2003) • 13,630 players added 1,271,451 labels to 293,760 images • became http://images.google.com/imagelabeler/since scaled up to hundred thousand+ players and 10’s of millionsof images labeled. Ahn and Dabbish (2004) Labeling images with a computer game, SIGCHI

Gene annotation games

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