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Three’s a crowd-source:
Observations on Collaborative
Genome Annotation.
Monica Munoz-Torres, PhD via Suzanna Lewis
Biocurator & Bioinformatics Analyst | @monimunozto
Genomics Division, Lawrence Berkeley National Laboratory
08 April, 2014 | 7th International Biocuration Conference
UNIVERSITY OF
CALIFORNIA
Outline 1. Automated and Manual Annotation in
a genome sequencing project.
2. Distributed, community-based
genome curation using Apollo.
3. What we have learned so far.
Three’s a crowd-
source:
Observations on
Collaborative
Genome Annotation.
Outline 2
Assembly
Manual
annotation
Experimental
validation
Automated
Annotation
In a genome sequencing project…
Automated Genome Annotation
1. Automated and Manual Annotation.
Gene prediction
Identifies elements of the genome using empiric and ab
initio gene finding systems. Uses additional experimental
evidence to identify domains and motifs.
Nucleic Acids 2003 vol. 31 no. 13 3738-3741
Curation [manual genome annotation editing]
1. Automated and Manual Annotation.
- Identify elements that best
represent the underlying
biological truth
- Eliminate elements that reflect
the systemic errors of
automated analyses.
- Determine functional roles
comparing to well-
studied, phylogenetically similar
genome elements via literature
and public databases (and
experience!).
Experimental Evidence:
cDNAs, HMM domain
searches, alignments with
assemblies or genes from other
species.
Computational analyses
Manually-curated Consensus
Gene Structures
Curators strive to achieve precise
biological fidelity.
1. Automated and Manual Annotation. 5
But! A single curator
cannot do it all:
- unmanageable scale.
- colleagues with
expertise in other
domains and gene
families are required.
iStockPhoto.com
Bring scientists together to:
- Distribute problem solving
- Mine collective intelligence
- Access quality
- Process work in parallel
Crowd-sourcing Genome Curation
“The knowledge and talents of a group of people is
leveraged to create and solve problems”
– Josh Catone | ReadWrite.com
Footer 6
(“crowdsourcing”, FreeBase.com)
Dispersed, community-based manual
annotation efforts.
We* have trained geographically dispersed
scientific communities to perform biologically
supported manual annotations: ~80
institutions, 14 countries, hundreds of
scientists using Apollo.
Education through:
– Training workshops and geneborees.
– Tutorials.
– Personalized user support.
2. Community-based curation. 7
*with Elsik Lab. University of Missouri.
What is Apollo?
• Apollo is a genomic annotation editing platform.
To modify and refine the precise location and structure of the
genome elements that predictive algorithms cannot yet
resolve automatically.
82. Community-based curation.
Find more about Web Apollo at
http://GenomeArchitect.org
and
Genome Biol 14:R93. (2013).
Web Apollo improves the
manual annotation environment
• Allows for intuitive annotation creation and editing with
gestures and pull-down menus to create and modify
coding genes and regulatory elements, insert comments
(CV, freeform text), etc.
• Browser-based, plugin for JBrowse.
• Edits in one client are instantly
pushed to all other clients.
• Customizable rules and
appearance.
92. Community-based curation.
Has the collaborative nature of manual
annotation efforts influenced research
productivity and the quality of
downstream analyses?
3. What we have learned. 10
Working together was helpful and
automated annotations were improved.
Scientific community efforts brought
together domain-specific and natural
history expertise that would have
otherwise remain disconnected.
Example:
>100 bovine cattle researchers
~3,600 manual annotations
3. What we have learned. 11
Nature Reviews Genetics 2009 (10), 346-
347
Science. 2009 (324) 5926, 522-528
Example:
Understanding the evolution of sociality.
Compared seven ant genomes for a better
understanding of evolution and organization
of insect societies at the molecular level.
Insights drawn mainly from six core aspects of
ant biology:
1. Alternative morphological castes
2. Division of labor
3. Chemical Communication
4. Alternative social organization
5. Social immunity
6. Mutualism
3. What we have learned. 12
The work of
groups of
communities led
to new insights.
Libbrecht et al. 2012. Genome Biology 2013, 14:212
New sequencing technologies pose
additional challenges.
Lower coverage leads to
– frameshifts and indel errors
– split genes across contigs
– highly repetitive sequences
To face these challenges, we train annotators in
recovering coding sequences in agreement with all
available biological evidence.
3. What we have learned. 13
Other lessons learned
1. You must enforce strict rules and formats; it is
necessary to maintain consistency.
2. Be flexible and adaptable: study and incorporate
new data, and adapt to support new platforms to
keep pace and maintain the interest of scientific
community. Evolve with the data!
3. A little training goes a long way! With the right
tools, wet lab scientists make exceptional curators
who can easily learn to maximize the generation of
accurate, biologically supported gene models.
3. What we have learned. 14
The power behind
community-based
curation of
biological data.
3. What we have learned. 15
Thanks!
• Berkeley Bioinformatics Open-source Projects
(BBOP), Berkeley Lab: Web Apollo and Gene
Ontology teams. Suzanna Lewis (PI).
• The team at Elsik Lab. § University of Missouri.
Christine G. Elsik (PI).
• Ian Holmes (PI). * University of California Berkeley.
• Arthropod genomics community, i5K
http://www.arthropodgenomes.org/wiki/i5K (Org.
Committee, NAL (USDA), HGSC-BCM, BGI), and
1KITE http://www.1kite.org/.
• Web Apollo is supported by NIH grants
5R01GM080203 from NIGMS, and 5R01HG004483
from NHGRI, and by the Director, Office of Science,
Office of Basic Energy Sciences, of the U.S.
Department of Energy under Contract No. DE-AC02-
05CH11231.
• Insect images used with permission:
http://AlexanderWild.com
• For your attention, thank you!
Thank you. 16
Web Apollo
Ed Lee
Gregg Helt
Justin Reese §
Colin Diesh §
Deepak Unni §
Chris Childers §
Rob Buels *
Gene Ontology
Chris Mungall
Seth Carbon
Heiko Dietze
BBOP
Web Apollo: http://GenomeArchitect.org
GO: http://GeneOntology.org
i5K: http://arthropodgenomes.org/wiki/i5K
ISB: http://biocurator.org

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Three's a crowd-source: Observations on Collaborative Genome Annotation

  • 1. Three’s a crowd-source: Observations on Collaborative Genome Annotation. Monica Munoz-Torres, PhD via Suzanna Lewis Biocurator & Bioinformatics Analyst | @monimunozto Genomics Division, Lawrence Berkeley National Laboratory 08 April, 2014 | 7th International Biocuration Conference UNIVERSITY OF CALIFORNIA
  • 2. Outline 1. Automated and Manual Annotation in a genome sequencing project. 2. Distributed, community-based genome curation using Apollo. 3. What we have learned so far. Three’s a crowd- source: Observations on Collaborative Genome Annotation. Outline 2 Assembly Manual annotation Experimental validation Automated Annotation In a genome sequencing project…
  • 3. Automated Genome Annotation 1. Automated and Manual Annotation. Gene prediction Identifies elements of the genome using empiric and ab initio gene finding systems. Uses additional experimental evidence to identify domains and motifs. Nucleic Acids 2003 vol. 31 no. 13 3738-3741
  • 4. Curation [manual genome annotation editing] 1. Automated and Manual Annotation. - Identify elements that best represent the underlying biological truth - Eliminate elements that reflect the systemic errors of automated analyses. - Determine functional roles comparing to well- studied, phylogenetically similar genome elements via literature and public databases (and experience!). Experimental Evidence: cDNAs, HMM domain searches, alignments with assemblies or genes from other species. Computational analyses Manually-curated Consensus Gene Structures
  • 5. Curators strive to achieve precise biological fidelity. 1. Automated and Manual Annotation. 5 But! A single curator cannot do it all: - unmanageable scale. - colleagues with expertise in other domains and gene families are required. iStockPhoto.com
  • 6. Bring scientists together to: - Distribute problem solving - Mine collective intelligence - Access quality - Process work in parallel Crowd-sourcing Genome Curation “The knowledge and talents of a group of people is leveraged to create and solve problems” – Josh Catone | ReadWrite.com Footer 6 (“crowdsourcing”, FreeBase.com)
  • 7. Dispersed, community-based manual annotation efforts. We* have trained geographically dispersed scientific communities to perform biologically supported manual annotations: ~80 institutions, 14 countries, hundreds of scientists using Apollo. Education through: – Training workshops and geneborees. – Tutorials. – Personalized user support. 2. Community-based curation. 7 *with Elsik Lab. University of Missouri.
  • 8. What is Apollo? • Apollo is a genomic annotation editing platform. To modify and refine the precise location and structure of the genome elements that predictive algorithms cannot yet resolve automatically. 82. Community-based curation. Find more about Web Apollo at http://GenomeArchitect.org and Genome Biol 14:R93. (2013).
  • 9. Web Apollo improves the manual annotation environment • Allows for intuitive annotation creation and editing with gestures and pull-down menus to create and modify coding genes and regulatory elements, insert comments (CV, freeform text), etc. • Browser-based, plugin for JBrowse. • Edits in one client are instantly pushed to all other clients. • Customizable rules and appearance. 92. Community-based curation.
  • 10. Has the collaborative nature of manual annotation efforts influenced research productivity and the quality of downstream analyses? 3. What we have learned. 10
  • 11. Working together was helpful and automated annotations were improved. Scientific community efforts brought together domain-specific and natural history expertise that would have otherwise remain disconnected. Example: >100 bovine cattle researchers ~3,600 manual annotations 3. What we have learned. 11 Nature Reviews Genetics 2009 (10), 346- 347 Science. 2009 (324) 5926, 522-528
  • 12. Example: Understanding the evolution of sociality. Compared seven ant genomes for a better understanding of evolution and organization of insect societies at the molecular level. Insights drawn mainly from six core aspects of ant biology: 1. Alternative morphological castes 2. Division of labor 3. Chemical Communication 4. Alternative social organization 5. Social immunity 6. Mutualism 3. What we have learned. 12 The work of groups of communities led to new insights. Libbrecht et al. 2012. Genome Biology 2013, 14:212
  • 13. New sequencing technologies pose additional challenges. Lower coverage leads to – frameshifts and indel errors – split genes across contigs – highly repetitive sequences To face these challenges, we train annotators in recovering coding sequences in agreement with all available biological evidence. 3. What we have learned. 13
  • 14. Other lessons learned 1. You must enforce strict rules and formats; it is necessary to maintain consistency. 2. Be flexible and adaptable: study and incorporate new data, and adapt to support new platforms to keep pace and maintain the interest of scientific community. Evolve with the data! 3. A little training goes a long way! With the right tools, wet lab scientists make exceptional curators who can easily learn to maximize the generation of accurate, biologically supported gene models. 3. What we have learned. 14
  • 15. The power behind community-based curation of biological data. 3. What we have learned. 15
  • 16. Thanks! • Berkeley Bioinformatics Open-source Projects (BBOP), Berkeley Lab: Web Apollo and Gene Ontology teams. Suzanna Lewis (PI). • The team at Elsik Lab. § University of Missouri. Christine G. Elsik (PI). • Ian Holmes (PI). * University of California Berkeley. • Arthropod genomics community, i5K http://www.arthropodgenomes.org/wiki/i5K (Org. Committee, NAL (USDA), HGSC-BCM, BGI), and 1KITE http://www.1kite.org/. • Web Apollo is supported by NIH grants 5R01GM080203 from NIGMS, and 5R01HG004483 from NHGRI, and by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02- 05CH11231. • Insect images used with permission: http://AlexanderWild.com • For your attention, thank you! Thank you. 16 Web Apollo Ed Lee Gregg Helt Justin Reese § Colin Diesh § Deepak Unni § Chris Childers § Rob Buels * Gene Ontology Chris Mungall Seth Carbon Heiko Dietze BBOP Web Apollo: http://GenomeArchitect.org GO: http://GeneOntology.org i5K: http://arthropodgenomes.org/wiki/i5K ISB: http://biocurator.org

Editor's Notes

  1. Outline. The box at the bottom is to give a context of automated and manual annotation as it will be discussed in this talk.
  2. Gene prediction identifies elements of the genome using either empiric or ab initio gene finding systems. Additional experimental evidence is used to identify domains and motifs, both at DNA and amino acid level.
  3. Curation here is understood in the context of manual genome annotation editing. It tries to find the best biological representation of gene models, while eliminating the most systematic errors of the automated analysis. Curation also helps to determine the functional roles of these genetic elements play by comparing them to well-studied, phylogenetically similar elements using literature and public databases, to distinguish orthologs from paralogs, and classifying their membership in families and networks.
  4. Precise biological fidelity in genome annotation editing cannot be achieved by a single individual. There are too many genes, making it an unmanageable scale, and curators need insights from colleagues with other expertise.
  5. SETI@Home tapped the unused processing power of millions of individual computers. Similarly, distributed labor networks are using the internet to exploit the spare processing power of millions of human brains.We are trying to empower genome researchers around the world to harness expertise from dispersed researchers. It could be just 3 researchers working together, that’s already a crowd!
  6. Although Computational analyses and experimental evidence from genomic features were available to build manually-curated consensus gene structures, all existent applications at the time imposed communications constrains on the curators. We created the tools to facilitate real-time interactivity and allow extensive changes without server round trips: Web Apollo.
  7. Apollo is a genomic annotation editing platform, and in its latest inception it is an evolution of a popular desktop version adopted by many research groups (insects, fish, mammals, birds, etc).
  8. Web Apollo improves the manual annotation environment. (then highlight the bulleted ideas).
  9. So, what have we learned so far?
  10. Previously disconnected researchers were more productive when obtaining immediate feedback in dialogs with collaborators.Also, automated annotations were improved as exemplified by discoveries made based on revised annotations, for example, ~3600 manual annotations contributed to a better understanding of immune function, reproduction, lactation, and metabolism in cattle.
  11. This is an example of how the collaborative nature of manual annotation has brought together an enormous group of scientists with very diverse interests, for the purpose of propelling discovery and a better understanding on the evolution and organization of insect societies at the molecular level. ~2800 manually annotated genes from three species of ants granted further insight into the evolution of sociality in this group.
  12. Unlike earlier genome projects, which had the advantage of more highly polished genomes, recent projects usually have lower coverage. Therefore curators now face additional work correcting for more frequent assembly errors and annotating genes that are split across multiple contigs.
  13. Highlight that the distributed nature of these efforts still demands strong, goal-oriented (i.e. publication of findings) leadership and coordination, as these are crucial to the success of each project.
  14. This slide brings together a collection of collaborative efforts, close to the work of many of the members of ISB, and other communities.i5K is the initiative to sequence the genomes of 5,000 arthropods. It currently is collaboratively – and simultaneously! - annotating the genomes of 6 insects using Web Apollo.
  15. Thank you!