Lewis isb 7 april2014

T H E W O R L D O F B I O C U R AT I O N

O P T I M I Z I N G I T S I M PA C T

April 7, 2014—Seventh International Biocuration Conference

S O M E O N E W H O I S R E S P O N S I B L E F O R T H E C A R E A N D S U P E R V I S I O N O F B I O L O G I C A L K N O W L E D G E R E S O U R C E S A N D T H E I R U S E

W H A T I S A B I O C U R A T O R ?

W H AT D O B I O C U R AT O R S D O T O D AY ?

• Credits to Kaveh Bazargan ᔥ

• @kaveh1000

F R U I T I N F O O D P R O C E S S O R

S M O O T H I E

R E S E A R C H

R E S E A R C H I N W O R D P R O C E S S O R

P D F

F R U I T ? ?

R E S E A R C H ? ?

?

R E S E A R C H ? ?

Y O U , T H E B I O C U R AT O R

B I O C U R AT O R S O F T H E W O R L D U N I T E !

• You have nothing to lose but your PDF files

!

! X

O U R R O L E I N T H E R E S E A R C H L I F E C Y C L E

T H E W O R L D O F B I O C U R A T I O N

http://www.nbcnews.com/id/49258816/ns/technology_and_science-science/t/live-concert-microbial-data-turned-song-lab/#.UzSB9ceT4_E

D E S I G N I N G E X P E R I M E N T S





http://www.langdonbiology.org/AP/labs/Notebook/AP_notebook.htm

C O L L E C T I N G D ATA

http://www.langdonbiology.org/AP/labs/Notebook/AP_notebook.htm

Thomas Nast - http://www.victorianweb.org/art/illustration/nast/51.jpg

W R I T I N G U P

R E S U LT S

http://www.victorianweb.org/art/illustration/nast/51.jpg

http://rrresearch.fieldofscience.com/2012_02_01_archive.html

R E V I E W I N G C O N C L U S I O N S

http://rrresearch.fieldofscience.com/2012_02_01_archive.html

C A P T U R I N G K N O W L E D G E

I S B


D E S I G N I N G E X P E R I M E N T S C O L L E C T I N G D ATA


W R I T I N G U P

R E S U LT S

~ 3 0 0 B I O C U R A T O R S

B I O C U R AT I O N I N V E R S I O N


C O L L E C T I N G D ATA

W R I T I N G U P R E S U LT S



http://www.nsf.gov/statistics/nsf13331/pdf/nsf13331.pdf

H U N D R E D S O F T H O U S A N D S O F G R A D S T U D E N T S

P O S T- D O C S

L A B O R AT O R I E S

J O U R N A L S

I N T H E L A B

E A R LY I N T E R V E N T I O N — S U P P O R T I N G S TA N D A R D S

• Promote community-accepted identifiers, ontologies, & formats

S U P P O R T S TA N D A R D S , T H E Y ’ R E O U R F R I E N D• November, 1999

• 45 biologists

• 14 days

• 140 megabases of Drosophila genome

!

• Published in March 2000

G E N E O N T O L O G Y, E T A L .

Q U E S T F O R O R T H O L O G S

questfororthologs.org/ — www.ebi.ac.uk/reference_proteomes

http://questfororthologs.org/

http://www.ebi.ac.uk/reference_proteomes


• 30 phylogenomic databases






• Vary in # of species, taxonomic range, sampling density, and methodology







• Joint benchmarking effort








• Only possible through the use of shared reference proteomes and formats








• Only possible through the use of shared reference proteomes and formats






• Develop and follow guidelines (paper and web-based)

• e.g. Gaudet, P., et al. Towards BioDBcore: a community-defined information specification for biological databases. Database 2011. PMCID: PMC3017395

• Resource Identification Initiative

• www.force11.org/Resource_identification_initiative

• Vasilevsky NA, et al. On the reproducibility of science: unique identification of research resources in the biomedical literature. PeerJ. 2013 Sep 5;1:e148. doi: 10.7717/peerj.148. PubMed PMID: 24032093; PubMed Central PMCID: PMC3771067.

http://www.force11.org/Resource_identification_initiative



• Embed community accepted standards in the lab environment

K N O C K O U T M O U S E P R O J E C T 2

• Broad standardized phenotyping of knockout mice on a standard genetic background

• Data collection from many centres

• www.mousephenotype.org

http://www.mousephenotype.org

K N O C K O U T M O U S E P R O J E C T 2

• Broad standardized phenotyping of knockout mice on a standard genetic background

• Data collection from many centres

• www.mousephenotype.org

Cindy Smith

http://www.mousephenotype.org

P R O T O C O L S A R E S TA N D A R D I Z E D

R E Q U I R E U S E O F PA R T I C U L A R O N T O L O G Y T E R M S T O D E S C R I B E P H E N O T Y P E




• Work with labs to embed standards into their data generation pipeline




• Stealth standards

S TA N D A R D S T H R O U G H U T I L I T Y — A P O L L O

C S I R O V I D E O — D E M O A T G E N O M E A R C H I T E C T. O R G

http://genomearchitect.org

S TA N D A R D S T H R O U G H U T I L I T Y — A P O L L O

C S I R O V I D E O — D E M O A T G E N O M E A R C H I T E C T. O R G

http://genomearchitect.org

T O O L S F O R T H E C O M M U N I T Y


• Web-based so researchers anywhere have access



• Concurrent access supports real-time collaboration




• Built-in support for standards (transparently compliant)





• Automatic generation of ready-made computable data





• Automatic generation of ready-made computable data

• Client-side application relieves server bottleneck and supports privacy




• Stealth standards

• Re-purpose internal curation tools for external users

• Provide on-line documentation, hands-on training and rapid-response user help

• Work with educators to make these tools an integral part of the curriculum

• e.g. CACAO (Critical Assessment of Community Annotation using Ontologies), ecoliwiki.net/colipedia/index.php/CACAO_0.1

• DNA subway (Apollo)

S U B M I S S I O N

• CANTO: curation.pombase.org

• Structured Digital Abstracts

• Identifiers for all named genes, proteins, metabolites or other objects in the article

• Main results described in simple ontology terms

• Experimental evidence types

• Not only a synopsis of the results but computer-readable

• Gerstein, M., et al. Structured digital abstract makes text mining easy. Nature 447, 142 (10 May 2007) | doi:10.1038/447142a.

• Minimal Information reporting guidelines

• http://mibbi.sourceforge.net/portal.shtml

S U B M I T T I N G D ATA — I N A S T R U C T U R E D W AY

http://curation.pombase.org

http://mibbi.sourceforge.net/portal.shtml

P U B L I S H I N G

P U B L I S H I N G

P U B L I S H I N G

• First there were letters

P U B L I S H I N G


• Then Henry Oldenburg created the first scientific journal in 1665

P U B L I S H I N G



• Result: too much to absorb

P U B L I S H I N G



• Result: too much to absorb

Washed away on the sea of information

P E E R A N D E D I T O R I A L R E V I E W B E C A M E A F I LT E R

C O N S E Q U E N T LY …

• Figshare: figshare.org

• iDigBio: www.idigbio.org

• Dryad: datadryad.org

• eLife: www.elifesciences.org

• Unlike journal articles, the scale of web-native publishing may overwhelm attempts at manual curation (using current strategies)

T H E M E D I U M O F P U B L I C AT I O N I S C H A N G I N G

http://figshare.org

http://datadryad.org

http://www.elifesciences.org/

D O W E N E E D T O C U R AT E ?

S C H O L A R S H I P : B E Y O N D T H E PA P E R . J A S O N P R I E M . N AT U R E 4 9 5 , 4 3 7 – 4 4 0 ( 2 8 M A R C H 2 0 1 4 )

“…powerful, online filters will distill communities impact judgements algorithmically”

S O M E S AY N O …


• Resolution of differences

• Clarity, eliminating noise

• Validation & design of automated methods

E V E N A P L A C E L I K E G O O G L E U S E S C U R AT O R S ( * A N D S O F T W A R E )

• Hundreds of operators per country

• Multiple kinds of errors: overlapping jurisdictions, accidental merges, road maps to satellite images mismatch, etc.

• Every road that you see has been hand-massaged

!

!

http://www.theatlantic.com/technology/archive/2012/09/how-google-builds-its-maps-and-what-it-means-for-the-future-of-everything/261913/

http://www.theatlantic.com/technology/archive/2012/09/how-google-builds-its-maps-and-what-it-means-for-the-future-of-everything/261913/





C L A R I T Y

• Answer boxes: Quick answers to concrete questions

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C L A R I T Y


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C L A R I T Y


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C L A R I T Y


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• Much of this information comes from Freebase which is structured in terms of entities and properties

C L A R I T Y


!

!

!

!

• Much of this information comes from Freebase which is structured in terms of entities and properties

Robert West, et al. Knowledge Base Completion via Search-Based Question Answering. http://www.cs.ubc.ca/~murphyk/Papers/www14.pdf WWW’14 April 7–11, 2014, Seoul, Korea. ACM 978-1-4503-2744-2/14/04. DOI:2568032

http://www.cs.ubc.ca/~murphyk/Papers/www14.pdf

http://dx.doi.org/10.1145/2566486.2568032





• PDF is still the dominant form of distribution

• PDF “Annotation”

• UTOPIA, www.utopiadocs.com

• DOMEO, swan.mindinformatics.org

• Textpresso, www.textpresso.org

• All of these are still lacking domain specifics (or need to be taught)

• FORCE11, www.force11.org

• Common goal is advancing scientific communications

• Beyond the PDF

L I T E R AT U R E I S I N F O R M AT I V E B U T I S N O T I N F O R M AT I O N

X

http://www.utopiadocs.com/

http://swan.mindinformatics.org

http://www.textpresso.org

http://www.force11.org

VA L I D AT I O N A N D D E S I G N O F A U T O M AT E D M E T H O D S



Write/modify software


Run the algorithm



Run the algorithm


Evaluate results


• Requires trusted reference datasets!

Run the algorithm


Evaluate results


• Requires trusted reference datasets!

• Biocurators are partners with developers!

Run the algorithm


Evaluate results

S C H O L A R S H I P : B E Y O N D T H E PA P E R . J A S O N P R I E M . N AT U R E 4 9 5 , 4 3 7 – 4 4 0 ( 2 8 M A R C H 2 0 1 4 )

“…powerful, online filters will distill communities impact judgements algorithmically”


T H E PA R A B L E O F G O O G L E F L U : T R A P S I N B I G D ATA A N A LY S I S . D AV I D L A Z E R E T A L . S C I E N C E 1 4 M A R C H 2 0 1 4 :

V O L . 3 4 3 N O . 6 1 7 6 P P. 1 2 0 3 - 1 2 0 5

“‘Big data hubris” is the often implicit assumption that big data are a substitute for, rather than a supplement

to, traditional data collection and analysis.”



• Yes

!

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• Yes

!

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• But…

S Y S T E M AT I C R E V I E W & C R I T I C I S M I S R E Q U I R E D

O U R S T R E N G T H I S I N Q U A L I T Y O F T H E I N F O R M A T I O N W E C A N P R O V I D E

C U S I C K , M . , E T A L . L I T E R AT U R E - C U R AT E D P R O T E I N I N T E R A C T I O N D ATA S E T S

N AT M E T H O D S . J A N 2 0 0 9 ; 6 ( 1 ) : 3 9 – 4 6 . P M C I D : P M C 2 6 8 3 7 4 5

“…literature curated datasets have inherent reliability difficulties…”

H O W C A N B I O C U R AT O R S A D D R E S S C R I T I C I S M S ?

G R E E N B E R G , S . , H O W C I TAT I O N D I S T O R T I O N S C R E AT E U N F O U N D E D A U T H O R I T Y: A N A LY S I S O F A C I TAT I O N N E T W O R K

B M J J U LY 2 0 0 9 ; 3 3 9 D O I : H T T P : / / D X . D O I . O R G / 1 0 . 1 1 3 6 /

T H E R I S K ( B Y A N A L O G Y )

56

http://dx.doi.org/10.1136/

W E ' R E R E S P O N S I B L E F O R T H E Q U A L I T Y

• “Reviewing the quality of the data is an obligation of any entity that assumes responsibility over the data.”

• Limor Peer et al., IDCC 2014

PA I N T A P O P T O S I S - S U M M A R Y

• 52 families annotated: - 8 were par$cipants in execution phase of apoptosis;

• 44 others are either:

A. upstream of apoptosis B. phenotypes C. targets

Example 1: Protein (cytochrome c) upstream of apoptosis execution

Cytochrome c is directly involved in apoptotic DNA fragmentation



➢ [Cells] – [cytochrome c] = No apoptotic DNA fragmentation



➢ [Cells] – [cytochrome c] = No apoptotic DNA fragmentation

➢ [Cells] – [cytochrome c] + [cytochrome c] = apoptotic DNA fragmentation

Example 2: Phenotype of reduced cell survival and increased DNA fragmentation

• E3 ubiquitin-protein ligase TRAF7 was annotated to execution phase of apoptosis

➢ Exogenous expression of TRAF7

➢ No other data in terms of where in apoptosis this may be. !

➢ All we know is altering TRAF7 levels affects apoptosis.

Example 3: TargetDSG2 was annotated to execution phase of apoptosis



DSG2 is a *target* of a protease (caspase), and although its degradation indeed seems to be a part of apoptosis it does not *mediate* apoptosis.

P R O V E T H E N E E D F O R B I O C U R AT I O N

• Publish: Quantitative improvements before/after

• Publish: Curator consistency studies

• Publish: Independent external reviews

R E C O G N I T I O N & C R E D I TO R C I D . O R G

http://orcid.org

E N A B L I N G R E S E A R C H

W H AT I S A B I O C U R AT O R ?




• A highly skilled and trained keeper of our biological heritage of knowledge.



• A content specialist who understands the research and can succinctly distill biological research results into computable data



• A content specialist who understands the research and can succinctly distill biological research results into computable data

• Considers the ease of finding this information, its relatedness to other information, and its research and educational usability

B6.Cg-‐Alms1foz/fox/J

increased weight, adipose tissue volume,

glucose homeostasis altered

ALSM1(NM_015120.4) [c.10775delC] + [-‐]

GENOTYPE

PHENOTYPE

obesity, diabetes mellitus, insulin resistance

increased food intake, hyperglycemia, insulin resistance

kcnj11c14/c14; insrt143/+(AB)

M O D E L S R E C A P I T U L AT E VA R I O U S P H E N O T Y P I C A S P E C T S O F D I S E A S E

B6.Cg-‐Alms1foz/fox/J

increased weight, adipose tissue volume,

glucose homeostasis altered

GENOTYPE

PHENOTYPE

obesity, diabetes mellitus, insulin resistance

increased food intake, hyperglycemia, insulin resistance

kcnj11c14/c14; insrt143/+(AB)

M O D E L S R E C A P I T U L AT E VA R I O U S P H E N O T Y P I C A S P E C T S O F D I S E A S E

?

R E S E A R C H R E S O U R C E SDoelken S C et al. Dis. Model. Mech. 2013;6:358-372

Smedley D et al. Database. 2013; bat025 Mungall CJ et al. Genome Biol. 2010; 11(1):R2 Washington N et al. Plos Biol 2009; e1000247

C R O S S - S P E C I E S P H E N O T Y P E C O M PA R I S O N S B Y S E M A N T I C S I M I L A R I T Y

CANDIDATE GENE PRIORITIZATION

PHENOTYPIC INTERPRETATION OF VARIANTS IN EXOMES (PHIVE)

Whole exome

Remove off-target and common variants

Variant score from allele freq and pathogenicity

Phenotype score from phenotypic similarity

PhenIX/PhIVE score to give final candidates

http://monarchinitiative.org

http://monarchinitiative.org

C O N F I R M E D D I A G N O S E S

• Infantile Parkinsonism-dystonia

• Wiedemann Steiner syndrome

• de novo SYNGAP1 mutation leading autosomal dominant mental retardation

• Frank-ter Haar syndrome

• Infantile hypophosphatasia

• … (~28%)

R E L AT E D N E S S A C R O S S B I O L O G Y


• Bio-Curator, not bio-Archivist

• Actively trying to represent current best understanding




• Support interoperability





• Support research and educational usability






• Support inference






• Support inference

• Not just for supporting searches, not just for finding PDF/online papers!

W H AT C A N B E D O N E ?





B I O D I V E R S I T Y D ATA J O U R N A L

B I O D I V E R S I T Y D ATA J O U R N A L

B I O D I V E R S I T Y D ATA J O U R N A LF R O M W R I T I N G , S U B M I S S I O N , P E E R - R E V I E W, E D I T I N G , P U B L I C AT I O N T O D I S S E M I N AT I O N !

W H AT C A N I S B D O ?


• Tangible support of standards efforts

• QfO, RII, MI, publish guidelines, validators …




• Create a curation mindset across the entire life cycle

• Support embedded/repurposed software, education, actively engage with text-miners, provide on-line support …






• Prove the necessity for curation

• Publish studies, greater emphasis on review and quality (assessment)






• Prove the necessity for curation

• Publish studies, greater emphasis on review and quality (assessment)

• Work with traditional publishers

• FORCE11, structured submissions

W H AT C A N Y O U D O ?

• Consider

• The ease of finding information

• Its relatedness to other information

• Its research and educational usability

R E S E A R C H ? ?

Y O U , T H E B I O C U R AT O R

I S B

A C K N O W L E D G E M E N T S A N D T H A N K SY O U A R E N O T A L O N E

Lewis isb 7 april2014

Data & Analytics

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r o n t o

g e n e o n t o

e i n t h e r e s e

o o t h i e

o r s d o t o d

p r o t o c o

o r i e s j o u r n