a centralized model organism database (cmod) for the long tail of sequenced genomes andrew su, ph.d....

A Centralized Model Organism Database (CMOD) for the Long Tail of Sequenced

Genomes

Andrew Su, Ph.D.@andrewsu

asu@scripps.eduhttp://sulab.org

January 16, 2014

GMOD 2014

OK

OK

Why am I giving this keynote?

2

3

http://www.flickr.com/photos/portland_mike/6140660504/

Harnessing the crowd…

4

… to organize information

http://www.flickr.com/photos/45697441@N00/6629580443

My simplified history of MODs5

My simplified history of MODs6

GMOD is widely used7

199 (!) organizations listed as GMOD users

Does the current model scale?8

Does the current model scale?9

1997

1998

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2018

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2025

1

10

100

1000

10000

100000

1000000

Bacteria

Eukaryotes

Archaea

Does the current model scale?10

# sequenced genomes

Year

Does the current model scale?11

The Long Tail of genomic data is being lost12

Identified 517 operons and 103 small regulatory RNAs...

The Long Tail of genomic data is being lost13

Identified 517 operons and 103 small regulatory RNAs...

At least you can download structured data…14

Centralized Model Organism Database concept15

CMOD

16

http://www.flickr.com/photos/aigle_dore/5626312363/

GMOD as a Service (GaaS)

17

http://www.flickr.com/photos/shannonmary/187131727/

Few genes are well annotated…18

Data: NCBI, February 2013

41%

65%

CTNNB1VEGFASIRT1FGFR2TGFB1TP53MEF2CBMP4LEF1WNT5ATNF

20,473 protein-coding genes

Genes, sorted by decreasing counts

GO

An

no

tati

on

C

ou

nts

1979

1980

1981

1982

1983

1984

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1986

1987

1988

1989

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1991

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0

200,000

400,000

600,000

800,000

1,000,000

Number of PubMed-indexed articles

… because the literature is sparsely curated?19

… because the literature is sparsely curated?20

0

1 0

2 0

Average capacity of human scientistNumber of articles read by typical scientist

21

311,696 articles (1.5% of PubMed)have been cited by GO annotations

22

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.

The Long Tail is a prolific source of content23

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

Wikipedia is reasonably accurate24

Wikipedia has breadth and depth25

http://en.wikipedia.org/wiki/Wikipedia:Size_comparisons, July 2008

Articles

Words(millions)

Wikipedia Britannica Online

26

We can harness the Long Tail of scientists to directly participate in

the gene annotation process.

Filtering, extracting, and summarizing PubMed

Documents

Concepts Review article

Filtering, extracting, and summarizing PubMed

Documents

Concepts

Wiki success depends on a positive feedback29

Gene wiki page utility

Number ofusers

Number ofcontributors

1001

2002

10,000 gene “stubs” within Wikipedia30

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

Gene Wiki has a critical mass of readers31

Total: 4.0 million views / month

Huss, PLoS Biol, 2008; Good, NAR, 2011

Utility

Users

Contributors

Gene Wiki has a critical mass of editors32

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

A review article for every gene is powerful33

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

Making the Gene Wiki more computable34

Structured annotationsFree text

Filling the gaps in gene annotation35

Wikilink

GO exact match

Gene Wiki mapping

NCBI Entrez Gene: 334

Candidate assertion

GO:0006897

6319 novel GO annotations2147 novel DO annotations

Gene Wiki content improves enrichment analysis36

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

Gene Wiki content improves enrichment analysis37

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

Gene Wiki content improves enrichment analysis38

p-value (PubMed only)

p-value (PubMed + GW)

Muscle contraction

More significant

PubMed + GW

More significant

PubMed only

The Long Tail of scientists is a valuable source of

information on gene function

39

http://fiehnlab.ucdavis.edu/projects/rice_metabolome/

Can we skip text mining?

Wikidata41

Provide a database of the world’s knowledge that

anyone can edit

- Denny Vrandečić

Wikidata understands scale42

Wikidata understands scale43

14 million Wikidata items…

…13 million total genes in Entrez Gene

Wikidata understands scale44

27 million Wikidata statements…

…150k total GO annotations

Wikidata for biology45

is a

regulates

Interacts with

Protein

Glycoprotein

Neural development

VLDL receptor

Amyloid precursor protein

Property:P31

Property:P128

Property:P129

Q8054

Q187126

Q1345738

Q1979313

Q423510

Q414043

Reelin

http://www.wikidata.org/wiki/Q414043

Wikidata for biology46

Property:P31

Property:P128

Property:P129

Q8054

Q187126

Q1345738

Q1979313

Q423510

Q414043

http://wikidata.org/w/api.php?action=wbgetentities&ids=Q414043&languages=en

Increasing biological data in Wikidata47

http://www.wikidata.org/wiki/Wikidata:Molecular_Biology_task_force

Loading genomic data into Wikidata48

Entrez Gene

Ensembl

UniProt

UCSC

PDB

RefSeq

Wikidata gene model49

Added ~1000 human genes so far….

Wikidata as CMOD?50

CMOD

Wikidata as CMOD?51

CMODPowered by:

CMOD

The Long Tail of

bioinformaticianscan collaboratively build a Centralized Model Organism

Database (CMOD).

52

53

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 LimMany Wikipedia editors

WP:MCB Project

Gene Wiki Collaborators

Katie FischBen GoodSalvatore Loguercio

Tobias MeissnerMax NanisChunlei Wu

Group members

Funding and Support

(BioGPS: GM83924, Gene Wiki: GM089820)

Contacthttp://sulab.org

asu@scripps.edu@andrewsu+Andrew Su

Adriel CarolinoErik ClarkeJon HussMarc LegliseMaximilian LudvigssonIan MacLeodCamilo Orozco

Key group alumni

Recruiting for student,

postdoc, outreach, and/or

staff positions!