5. Gene prediction is
challenging
Some examples:
• missing exon
• truncated or overextended exon
• gene split into several gene predictions (e.g. if
introns are very large)
• merged genes (two adjacent gene models are
predicted to be a single “megagene”)
6. Incorrect Gene Prediction is
Problematic
• studying gene family evolution
• RNAseq analyses
• molecular evolution analyses
7. Manual curation
• yields the best gene models
• is time consuming
• plausible for large communities (e.g. Human, C.
elegans)
• but what if a small lab sequenced their favorite bug’s
genome?
16. Foldit players contribute to
real science!
• Christopher B Eiben et al (2012) Increase Diels-Alderase
activity through backbone remodelling guided by Foldit
players. Nature Biotechnology.
• Firas Khatib et al (2011) Crystal structure of a monomeric
retroviral protease solved by protein folding game players.
Nature Structural and Molecular Biology.
• Firas Khatib et al (2011) Algorithm discovery by protein
folding game players. Proceeding of the National Academy of
Sciences.
17. Crowdsourcing works
• GalaxyZoo volunteers have discovered real
galaxies.
• Foldit players have guided real scientific
questions.
20. Lower the entry barrier to
contribution
• contributors refine one gene model at a time
• present gene model based on user’s experience –
beginners see easy to curate models
• tutorial or learning tasks
• assisting UI
21. Social network
• Passive recruitment: post curation activities of
contributors to social network.
• Cathy contributed to cancer research by refining three
gene models. Can you help too?
• Mike helped researchers understand how ant societies
are organised by refining two gene models.
• Amos earned the “expert gene curator badge” by curating
1000 gene models.
• Active recruitment of friends on social network.
23. Retaining contributors
Learning experience
Helping science
Prestige & pride:
• points and badges.
• being featured on our leaderboard.
• acknowledgement or coauthorship in publication
• responsibility: “senior” contributors are
• asked to arbitrate between conflicting submissions of junior
contributors.
• asked to curate a specific set of genes (developing expertise)
25. Begin
Create initia t asks
Needs curatio
n l
Curate Curate Curate
Being curated Being curated Being curated
Submit Submit Submit
te
t: crea
isten task
ons iew”
Inc rev
“
Auto-check
Consistent:
create next required task
Done
26. Ensure quality gene
models
• make tasks small & simple
• beginners are trained
• redundant curation
• review of conflicts by experienced users.
28. Summary
• many emerging model organsims are being studied
• gene prediction hasn’t caught up yet
• manual curation requires huge amount of time
• crowdsourcing exists
• crowdsourcing works – even in science
• there are many challenges
• work in progress
32. Summing up
• 180+ eukaryotic genomes and more coming
• gene prediction hasn’t caught up
• best gene models are manually curated
• manual curation can take hours to days
• curating a full genome can take years
Editor's Notes
In the last 10 years the cost of sequencing a genome has gone down from 100M USD to 10K USD.
Sequencing genomes is now inexpensive. 10K USD – roughly 4 months of a PhD student’s salary – anyone can sequence an organism and start studying it.
Deriving a set of genes from the genome, gene prediction, can be done ab-initio or by looking
Studying gene family evolution -> to determine if gene duplication occurred.RNAseq analyses -> because you can only compare the expression of genes you knowFor analyses, gene models must be inspected and refined.
Problems of this scale, difficult for computers but easily approachable with human intelligence, have been successfully crowdsourced.
Where the combined time, and effort, and intelligence of people – real people – has been successfully utilized to solve “hard” problems.
Hanny’sVoorwerp, discovered in 2007, by Dutch school teacher Hanny van Arkel, while she was participating as an amateur volunteer in the GalaxyZoo project.
http://fold.it/portal/info/about#folditpub.At least four publications, in high impact factor journal, leading to the discovery of ….
Perhaps. What would the challenges be?
We understand it might not be possible to lower the entry barrier so that anybody can start contributing, so we start by “inviting” undergrad Biologists as beta-testers. Biology undergrads would know the underlying Biology, but uninitiated to sequence curation.If somebody asks: one professor can give a few sequence curation tasks as homework assignment.A b
Instill a sense of contribution to greater good.Instill curiosity in the scientific oriented kids.Thereby bringing in more contribution.Active recruitement of peers on social network
Dr. YannickWurm and I, back at Queen Mary, University of London are trying to build a system to crowdsource manual curation. We have setup a home page at afra.sbcs.qmul.ac.uk to explain what we are doing and will continue to post updates there as we make progress.
