crowdsourcing biology: the gene wiki, biogps and genegames.org (sanger)
TRANSCRIPT
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Crowdsourcing Biology: The Gene Wiki, BioGPS and GeneGames.org
Andrew Su, Ph.D.@andrewsu
[email protected]://sulab.org
Sanger/EBI
September 7, 2012
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Few genes are well annotated…2
38%
59%
TP53TNFAPOEMTHFRIL6HLA-DRB1VEGFAEGFRTGFB1ACE
Data: NCBI gene2pubmed, August 2010
23,278 protein-coding genes
Genes, sorted by decreasing counts
Co
un
ts
Gene ontology
PubMed
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200,000
400,000
600,000
800,000
1,000,000
Number of PubMed-indexed articles
… because the literature is sparsely curated?3
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… because the literature is sparsely curated?4
0
1 0
2 0
Average capacity of human scientistNumber of articles read by typical scientist
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5
311,696 articles (1.5% of PubMed)have been cited by GO annotations
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0
Sooner or later, the research community will
need to be involved in the annotation effort to scale
up to the rate of data generation.
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The Long Tail is a prolific source of content7
ShortHead
Long Tail
Content produced
Contributors (sorted)
News :Video:
Product reviews:Food reviews:Talent judging:
NewspapersTV/Hollywood
Consumer reportsFood criticsOlympics
BlogsYouTube
Amazon reviewsYelp
American Idol
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Wikipedia is reasonably accurate8
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Wikipedia has breadth and depth9
http://en.wikipedia.org/wiki/Wikipedia:Size_comparisons, July 2008
Articles
Words(millions)
Words/ article
Wikipedia Britannica Online
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10
We can harness the Long Tail of scientists to directly participate in
the gene annotation process.
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From crowdsourcing to structured data11
The Gene Wiki
Biological Games
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Filtering, extracting, and summarizing PubMed
Documents
Concepts
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Wiki success depends on a positive feedback13
Gene wiki page utility
Number ofusers
Number ofcontributors
1001
2002
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10,000 gene “stubs” within Wikipedia14
Protein structure
Symbols and identifiers
Tissue expression pattern
Gene Ontology annotations
Links to structured databases
Gene summary
Protein interactions
Linked references
Huss, PLoS Biol, 2008
Utility
Users
Contributors
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Gene Wiki has a critical mass of readers15
Total: 5.0 million views / month
Huss, PLoS Biol, 2008; Good, NAR, 2011
Utility
Users
Contributors
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Gene Wiki has a critical mass of editors16
Increase of ~10,000 words / month from >1,000 editsCurrently 1.42 million words
Approximately equal to 230 full-length articles
Good, NAR, 2011
Utility
Users
Contributors
Edi
tor
coun
t Editors
Edits Edi
t co
unt
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A review article for every gene is powerful17
References to the literature
Hyperlinks to related conceptsReelin: 98 editors, 703 edits since July 2002
Heparin: 358 editors, 654 edits since June 2003
AMPK: 109 editors, 203 edits since March 2004
RNAi: 394 editors, 994 edits since October 2002
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Making the Gene Wiki more reliable18
The company name is derived from old Greek, and means
"destroyer of birds".
Novartis is a multinational pharmaceutical company
based in Basel, Switzerland that manufactures drugs such
as clozapine (Clozaril), diclofenac (Voltaren), …
2
2
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Making the Gene Wiki more reliable19
http://www.wikitrust.net/
The company name is derived from old Greek, and means
"destroyer of birds".
Novartis is a multinational pharmaceutical company
based in Basel, Switzerland that manufactures drugs such
as clozapine (Clozaril), diclofenac (Voltaren), …
*
36211 total edits 36 total edits
High-trust author Low-trust author
******
** *
*
*
**
2
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Making the Gene Wiki more computable20
Structured annotationsFree text
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Filling the gaps in gene annotation21
Wikilink
GO exact match
Gene Wiki mapping
NCBI Entrez Gene: 334
Candidate assertion
GO:0006897
6319 novel GO annotations2147 novel DO annotations
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22
TOP 100 GENES
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Gene Wiki content improves enrichment analysis23
GO term
Gene listConcept
recognitionPubMed abstracts
Enrichment analysis
GO:0007411
axon guidance
(GO:0007411)
264 genes
Linked genes through PubMed
P = 1.55 E-20
811 articles
Yes No
Yes 13 2
No 251 12033
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Gene Wiki content improves enrichment analysis24
GO term
Gene listConcept
recognitionPubMed abstracts
Gene Wiki
+
Enrichment analysis
GO:0006936 GO:0006936
muscle contraction
(GO:0006936)
87 genes
Linked genes through PubMed
Linked genes through
PubMed + Gene Wiki
P = 1.0 P = 1.22 E-09
251 articles
87 articles
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Gene Wiki content improves enrichment analysis25
p-value (PubMed only)
p-value (PubMed + GW)
Muscle contraction
More significant
PubMed + GW
More significant
PubMed only
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Gene Wiki+: Crowdsourced semantic database26
Q: What genes are related to hemolytic anemia?
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The Long Tail of scientists is a valuable source of
information on gene function
27
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From crowdsourcing to structured data28
The Gene Wiki
Biological Games
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Gene databases are numerous and overlapping29
… and hundreds more …
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http://biogps.org
Community extensibility and user customizability30
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Utility
UsersContributors
Utility: A simple and universal plugin interface31
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Utility
UsersContributors
Utility: A simple and universal plugin interface32
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Utility
UsersContributors
Utility: A simple and universal plugin interface33
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Utility
UsersContributors
Utility: A simple and universal plugin interface34
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Utility
UsersContributors
Utility: A simple and universal plugin interface35
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Utility: A simple and universal plugin interface36
Utility
UsersContributors
Total of 389 gene-centric online databases registered as BioGPS plugins
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Users: BioGPS has critical mass37
• > 4100 registered users• 4000 unique visitors per week• 40,000 page views per week
1. Harvard2. NIH3. UCSD4. Scripps5. MIT6. Cambridge
7. U Penn8. Stanford9. Wash U10. UNC
Top 10 organizations
Daily pageviewsUtility
UsersContributors
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Contributors: Explicit and implicit knowledge38
389 plugins registered (65% publicly shared)
by over 75 users
spanning 150+ domains
Utility
UsersContributors
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Mining structured content from HTML39
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Defining a data extraction template40
…
TP53 TNF APOE IL6 VEGF …EGFR TGFB1
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The Long Tail of
bioinformaticianscan collaboratively build a gene portal.
42
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From crowdsourcing to structured data43
The Gene Wiki
Biological Games
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44
http://www.flickr.com/photos/archana3k1/4124330493/
Seven million human hours
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45
Twenty million human hours
http://www.flickr.com/photos/ableman/2171326385/
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-46
150 billion human hours
http://www.flickr.com/photos/rvp-cw/6243289302/
per year
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Using games to fold proteins47
Fold.it players have successfully:• Outperformed state of the art protein
folding algorithms (Cooper, Nature, 2010)
• Solved a previously-intractable crystal structure (Khatib, Nat Struct Mol Biol, 2011)
• Designed an improved protein folding algorithm (Khatib, PNAS, 2011)
• Improved enzyme activity of de novo designed enzyme (Eiben, Nat Biotechnol, 2011)
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No good gene-disease annotation database51
Alzheimer's disease (AD)Lipoprotein glomerulopathySea-blue histiocyte disease
Query: Apolipoprotein E
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No good gene-disease annotation database52
Alzheimer's disease (AD)Lipoprotein glomerulopathy Sea-blue histiocyte diseaseHyperlipoproteinemia, type IIIMacular degeneration, age-relatedMyocardial infarction susceptibility
Query: Apolipoprotein E
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No good gene-disease annotation database53
Alzheimer's disease (AD)Lipoprotein glomerulopathy Sea-blue histiocyte diseaseHyperlipoproteinemia, type IIIMacular degeneration, age-relatedMyocardial infarction susceptibilityHIVPsoriasisVascular Diseases
Query: Apolipoprotein E
?
?
?
?
?
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No good gene-disease annotation database54
Alzheimer's disease (AD)Neuropsychological Tests Cognition Disorders Dementia Cognition Disease Progression Cardiovascular Diseases Coronary Disease Diabetes Mellitus, Type 2 Memory Disorders
Query: Apolipoprotein E
Memory Coronary Artery Disease Hypertension Mental Status Schedule Psychiatric Status Rating
Scales Hyperlipidemias Atrophy Dementia, Vascular Parkinson Disease Brain Injuries Myocardial Infarction …
477 diseases!
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Play Dizeez to annotate gene-disease links55
3. If it’s ‘right’, you get points
4. Then on to the next question…
2. Click the related disease (only one is “right”)
5. Hurry!
1. Read the clue (gene)
6. Play to win!
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Dizeez players seem pretty smart…56
In total (since Dec 2011):• 207 unique gamers• 1045 games played• 8525 guesses
# Occurrences Gene Disease
7 GAST gastrinoma
7 RBP3 retinoblastoma
7 SSX1 synovial sarcoma
6 TG Graves' disease
6 CRYGC Cataract
6 SOX8 mental retardation
6 WRN Werner syndrome
6 ABL1 leukemia
6 MLL3 leukemia
6 SNAI2 breast carcinoma
Pubmed OMIM PharmGKB Gene Wiki
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Dizeez players seem pretty smart…57
# Occurrences Gene Disease
5 MECOM sarcoma
4 ATF7 cancer
3 ABCB5 acute myeloid leukemia
3 SART1 glioblastoma
3 NCK1 leukemia
3 NEK1 cancer
Pubmed OMIM PharmGKB Gene Wiki
In total (since Dec 2011):• 207 unique gamers• 1045 games played• 8525 guesses
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Using games to predict phenotype from genotype?58
http://genegames.org
The Cure
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Classification problems in genome biology59
cancer normal
find patterns
Classify new samples
cancer
normalSVM
Neural networks
Naïve Bayes
KNN
…100s samples
100,
000s
fea
ture
s
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Random forests60
Sample subset of cases and
featuresTrain decision
treecancer normal
100s samples
100,
000s
fea
ture
s
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Random forests61
cancer normal
100s samples
100,
000s
fea
ture
s
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Random forests62
Classify new samples
cancer
normal
cancer normal
100s samples
100,
000s
fea
ture
s
How to interject biological
knowledge?
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Network-guided forests63
Dutkowski & Ideker (2011). PLoS Computational Biology
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Network-guided forests64
Sample features by PPI
networkTrain decision
treecancer normal
100s samples
100,
000s
fea
ture
s
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Human-guided forests65
Sample features by
human intelligence
Train decision treecancer normal
100s samples
100,
000s
fea
ture
s
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66
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The Cure: Genomic predictors for disease67
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The Cure: Genomic predictors for disease68
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The Cure: Genomic predictors for disease69
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The Cure: Genomic predictors for disease70
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The Cure: Genomic predictors for disease71
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The Cure: Genomic predictors for disease72
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Human-guided forests73
Classify new samples
cancer
normal
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“Critical Assessment”-style challenge74
Will this work? Check our blog after October 15.
Coming soon to genegames.org
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The Long Tail of gamerscan collaboratively build an accurate disease classifier.
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Doug Howe, ZFINJohn Hogenesch, U PennJon Huss, GNFLuca de Alfaro, UCSCAngel Pizzaro, U PennFaramarz Valafar, SDSUPierre Lindenbaum,
Fondation Jean DaussetMichael Martone, RushKonrad Koehler, Karo BioWarren Kibbe, Simon Lim, NorthwesternMany Wikipedia editors
WP:MCB Project
Collaborators
Ben GoodSalvatore LoguercioIan Macleod
Max NanisChunlei Wu
Group members
Funding and Support
(BioGPS: GM83924, Gene Wiki: GM089820)
Contacthttp://sulab.org
[email protected]@andrewsu+Andrew Su
Recruiting graduate students in quantitative biology! See http://education.scripps.edu/
@genegame