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Nathan	A.	Dunn
1
,	Monica	C.	Munoz-Torres
1
,	Deepak	
Unni
2
,	Eric	Yao
3
,	Colin	Diesh
2
,	Ian	Holmes
3
,	Christine	
G.	E...
ge nom e arc hite c t. org
Genome	Annotation
Structural	Annotation	
• exons,	introns,	UTRs	
• repeat	regions	
• transposab...
ge nom e arc hite c t. org
Functional	Annotation	
• metabolic	pathways	/	functions	
• Gene	Ontology	
• molecular	function	...
ge nom e arc hite c t. org
Example	Genome	Analysis	Workflow
4
Experimental design,
sampling
Comparative analyses
Curated
G...
ge nom e arc hite c t. org
Experimental design,
sampling
5
Consensus
Gene Set
Automated
Annotation
Sequencing
Synthesis &
...
ge nom e arc hite c t. org
Integration	into	Workflow	and	Tools
6
• Over	100	organizations	refine	annotation		
• Multiple	g...
ge nom e arc hite c t. org
Automated	Identification	is	not	Perfect
7
Automated
Annotation
Generation	of	Gene	Models	
Find	...
ge nom e arc hite c t. org
Human Analysis
Automated
Annotation
Manual	Annotation	Refines	Genome
8
Experimental Evidence
cD...
ge nom e arc hite c t. org
9
Annotators
Apollo
Google Web Toolkit
(GWT) / Bootstrap
Apollo	is	a	Tool	for	Collaborative	Ann...
ge nom e arc hite c t. org
1	-	Evidence	Viewer		/	Genome	Browser
10
Evidence	
Transcripts	
	(GFF3,	GBK)
BAM	Reads
Transcri...
ge nom e arc hite c t. org
1	-	Evidence	Viewer	(Genome	Browser)
11
Dynamically	Open
Configure	Multiple	Tracks
			addStores...
ge nom e arc hite c t. org
2	-	Genome	Annotation	Editor
12
Transcripts	
	(GFF3,	GBK)
BAM	Reads
Transcripts	
	(GFF3,	GBK)
B...
ge nom e arc hite c t. org
13
Alignments	shown	in	red
Annotate	other	genomic	
types	with	drop-down
Create	Annotation
Add	A...
ge nom e arc hite c t. org
Edit	Annotation	Structure
14
Adjust	exon	by	dragging
ge nom e arc hite c t. org
Editing	Annotations
15
Edit	Additional		
Structural	Data	
(right-click	popup)
Edit	Associations...
ge nom e arc hite c t. org
Edit	Annotation	Structure
16
Revertible	History	of	Structural	Operations
Current	position
Highl...
ge nom e arc hite c t. org
Annotate	Reference	Sequence	Alterations
17
Alteration	Reflected
ge nom e arc hite c t. org
18
Search
View	/	Edit	Details
List	/	Navigate	Vertically
Collapsible
3	-	Annotator	Panel
Link	t...
ge nom e arc hite c t. org
Reference	Sequence	-	Search	and	Export
19
Search
Navigation
Export	Annotations
ge nom e arc hite c t. org
Organism:	Configuration
20
Import	JBrowse	directory
Share	“Public”	organisms
Genome	Res.	2009	S...
ge nom e arc hite c t. org
Admin:	Users	and	Groups
21
Add	/	Search	Users	
Edit	User	
Permission
User	Can	“Admin”	an	Organi...
ge nom e arc hite c t. org
Apollo	Server	-	Grails
Security
Architecture
22
Web	Services	Client
Perl,	Shell,	Groovy,	PHP,	e...
ge nom e arc hite c t. org
Apollo	Server	-	Grails
Security
Architecture
23
Web	Services	Client
Perl,	Shell,	Groovy,	PHP,	e...
ge nom e arc hite c t. org
Apollo	Server	-	Grails
Security
Architecture
24
Web	Services	Client
Perl,	Shell,	Groovy,	PHP,	e...
ge nom e arc hite c t. org
Apollo	Server	-	Grails
Security
Architecture
25
Web	Services	Client
Perl,	Shell,	Groovy,	PHP,	e...
ge nom e arc hite c t. org
Apollo	Server	-	Grails
Security
Architecture
26
Web	Services	Client
Perl,	Shell,	Groovy,	PHP,	e...
ge nom e arc hite c t. org
Summary
Annot
ators
Apollo
Google Web Toolkit
(GWT) / Bootstrap
Apollo
Google Web Toolkit
(GWT)...
ge nom e arc hite c t. org
*	Coordinate	
Transformation
Future	Work:	Coordinate	Transform
28
Mavenize
Web	Apollo
Desktop	A...
ge nom e arc hite c t. org
Combine	Scaffolds
Lock	and	Orient	Combined	Scaffolds
Used	Scaffolds
Set	Orientation
Select	to	
...
ge nom e arc hite c t. org
Combine	Scaffolds
View	Individual	Features
ge nom e arc hite c t. org
Variant	Annotation	and	Visualization
Mavenize
Web	Apollo
Desktop	Apollo
DB	backend,	Sidebar,	
G...
• Berkeley	Bioinformatics	Open-source	Projects	(BBOP),	
Berkeley	Lab:	Apollo	and	Gene	Ontology	teams.	Suzanna	E.	
Lewis	(P...
Extra	Slides
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Apollo — Collaborative and Scalable Manual Genome Annotation

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Manual curation is crucial to improving the quality of the annotations of a genome. It enables curators to refine automated gene predictions using experimental data and aligned predictions from closely related organisms to more accurately represent the underlying biology. Apollo is a web-based genome annotation editor that allows curators to manually revise and edit the structure and function of predicted genomic elements.
Apollo, built on top of the JBrowse genome browser, offers an ‘Annotator Panel’ that allows users to efficiently navigate the genome and its annotations. Changes are reflected in real-time to all users (similar to Google Docs) and aggregated in a revertible, visual history of structural edits. Apollo allows the export of sequences and metadata associated with each annotated genomic element in FASTA, GFF3, or Chado. A single Apollo server can be scaled to support multiple genome projects and curators. Access to genomes is controlled with fine-grained permissions (e.g. administrator, curator, public). To support integration into larger workflows, we expose the suite of web services that drives user-interface functionality. These web- services have been leveraged to integrate with Docker and the Galaxy platform.
Striving to increase Apollo’s repertoire of visual exploration and exploratory analytics tools, two major undertakings are currently under development. First, the ability to visualize variant data and to annotate their predicted effects, primarily on coding regions. New technology trends and scientific paradigms point to new needs in genomic analytic tools to leverage information about variants that impact human health. Driven by a growing need to identify disease causing variants across diverse groups, we are working towards providing full functionality in genomic variant analysis and curation. Second, is the transformation of separate genomic coordinates into a single, synthetic region. This will allow the visualization of two or more genomics regions, from the length of entire chromosomes to just a few exons, within an artificially constructed genomic region. Artificially joining scaffolds facilitates annotation of genomic features split across two or more regions of a fragmented assembly (e.g, scaffolds), likely informing potential improvements to the genome assembly in the process. Additionally, this will allow hiding (visual genome folding) intra- and intergenic regions to provide a more information-rich visualization of the genome. For example, bringing exons closer together will facilitate annotating gene models with long introns, as sequences at the edge of exons separated by thousands of base-pairs will be shown adjacently.
Apollo is currently being used in over one hundred genome annotation projects around the world, ranging from annotation of a single species to lineage-specific efforts supporting the annotation of dozens of species at a time.

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Apollo — Collaborative and Scalable Manual Genome Annotation

  1. 1. Nathan A. Dunn 1 , Monica C. Munoz-Torres 1 , Deepak Unni 2 , Eric Yao 3 , Colin Diesh 2 , Ian Holmes 3 , Christine G. Elsik 2 and Suzanna E. Lewis 1 (1) Lawrence Berkeley National Laboratory, Berkeley, CA, (2) Division of Animal Sciences, University of Missouri, Columbia, MO, (3) Department of Bioengineering, Berkeley, CA Apollo — Collaborative and Scalable Manual Genome Annotation https : //g ithub. org / G M O D /A pollo/ http: //ge nom e arc hite c t. org / @apollo_bbop
  2. 2. ge nom e arc hite c t. org Genome Annotation Structural Annotation • exons, introns, UTRs • repeat regions • transposable elements • tRNA, snRNA, snoRNA, miRNA, ncRNA, rRNA 2 Functional Annotation • metabolic pathways / functions • Gene Ontology • molecular function • biological process • cellular component • expression • gene families http://geneontology.orgPhoto Credit: Alex Wild at http://www.alexanderwild.com/
  3. 3. ge nom e arc hite c t. org Functional Annotation • metabolic pathways / functions • Gene Ontology • molecular function • biological process • cellular component • expression • gene families Genome Annotation Structural Annotation • exons, introns, UTRs • repeat regions • transposable elements • tRNA, snRNA, snoRNA, miRNA, ncRNA, rRNA 3http://geneontology.orgPhoto Credit: Alex Wild at http://www.alexanderwild.com/
  4. 4. ge nom e arc hite c t. org Example Genome Analysis Workflow 4 Experimental design, sampling Comparative analyses Curated Gene Set Manual Annotation Sequencing Synthesis & dissemination Create Assembly FGENESH Automated Annotation
  5. 5. ge nom e arc hite c t. org Experimental design, sampling 5 Consensus Gene Set Automated Annotation Sequencing Synthesis & dissemination FGENESH Example Genome Analysis Workflow Create Assembly Analyses need Quality Data Comparative analyses Annotation Manual Annotation
  6. 6. ge nom e arc hite c t. org Integration into Workflow and Tools 6 • Over 100 organizations refine annotation • Multiple genomes per organization NCBI Ensemble Refined Annotations Distributed to Public
  7. 7. ge nom e arc hite c t. org Automated Identification is not Perfect 7 Automated Annotation Generation of Gene Models Find ORFs, multiple rounds of gene prediction Annotation of Gene Models
 Predicting function, expression patterns, metabolic network memberships • Assembly errors can cause fragmented annotations • Limited coverage makes precise identification difficult Manual Annotation
  8. 8. ge nom e arc hite c t. org Human Analysis Automated Annotation Manual Annotation Refines Genome 8 Experimental Evidence cDNAs, HMM domain searches, RNAseq, genes from other species. • Additional data • Biological knowledge • Curator best represents underlying evidence Manual Annotation
  9. 9. ge nom e arc hite c t. org 9 Annotators Apollo Google Web Toolkit (GWT) / Bootstrap Apollo is a Tool for Collaborative Annotation Annotators Apollo Google Web Toolkit (GWT) / Bootstrap Annotators Apollo Google Web Toolkit (GWT) / Bootstrap • Web-based Editor • Real-time collaborative • Easy to use • genomic browser Photo Credits: i5K; Alex Wild at http://www.alexanderwild.com/: leaf cutter ant, ensign wasp; Leo Bukeboom: Nasonia vitripennis jewel wasp; Wikimedia Commons: Apis mellifera honey bee; Mike MacNeil USDA/ARS Fort Keogh LARRL: Bos taurus cow.
  10. 10. ge nom e arc hite c t. org 1 - Evidence Viewer / Genome Browser 10 Evidence Transcripts (GFF3, GBK) BAM Reads Transcripts (GFF3, GBK) BigWig XY BigWig HeatMap Themes (dark/light) Color CDS Frame Automated Annotation Manual Annotation
  11. 11. ge nom e arc hite c t. org 1 - Evidence Viewer (Genome Browser) 11 Dynamically Open Configure Multiple Tracks addStores={"url":{"type":"JBrowse/Store/SeqFeature/ GFF3","urlTemplate":"http://host/genes.gff"}} &addTracks=[{"label":"genes","type":"JBrowse/View/ Track/CanvasFeatures","store":"url"}] Append via URL Statically Configure • BAM • BigWig • GFF • GTF • GBK • VCF • FASTA • FASTAi • SPARQL • custom types (e.g., REST end- point) https://gmod.github.io/jbrowse-registry/
  12. 12. ge nom e arc hite c t. org 2 - Genome Annotation Editor 12 Transcripts (GFF3, GBK) BAM Reads Transcripts (GFF3, GBK) BigWig XY BigWig HeatMap Automated Annotation Manual Annotation Exported Refined Genomic Elements
  13. 13. ge nom e arc hite c t. org 13 Alignments shown in red Annotate other genomic types with drop-down Create Annotation Add Annotation by Dragging a Genomic Element
  14. 14. ge nom e arc hite c t. org Edit Annotation Structure 14 Adjust exon by dragging
  15. 15. ge nom e arc hite c t. org Editing Annotations 15 Edit Additional Structural Data (right-click popup) Edit Associations • PubMed / dbxref • Gene Ontology • Metadata • key/value • status • comments Change Annotation Type History of Structural Edits
  16. 16. ge nom e arc hite c t. org Edit Annotation Structure 16 Revertible History of Structural Operations Current position Highlighted row shown
  17. 17. ge nom e arc hite c t. org Annotate Reference Sequence Alterations 17 Alteration Reflected
  18. 18. ge nom e arc hite c t. org 18 Search View / Edit Details List / Navigate Vertically Collapsible 3 - Annotator Panel Link to Location Alternate Annotations View
  19. 19. ge nom e arc hite c t. org Reference Sequence - Search and Export 19 Search Navigation Export Annotations
  20. 20. ge nom e arc hite c t. org Organism: Configuration 20 Import JBrowse directory Share “Public” organisms Genome Res. 2009 Sep;19(9):1630-8. doi: 10.1101/gr.094607.109 Create JBrowse tracks from FASTA / GFF3 / BAM / BigWig
  21. 21. ge nom e arc hite c t. org Admin: Users and Groups 21 Add / Search Users Edit User Permission User Can “Admin” an Organism Use Groups to Manage Bulk Permissions
  22. 22. ge nom e arc hite c t. org Apollo Server - Grails Security Architecture 22 Web Services Client Perl, Shell, Groovy, PHP, etc. Annotators Apollo Google Web Toolkit (GWT) / BootstrapJBrowse DOJO / jQuery WebSocket JDBC File System Apollo Client(s) Server REST
  23. 23. ge nom e arc hite c t. org Apollo Server - Grails Security Architecture 23 Web Services Client Perl, Shell, Groovy, PHP, etc. Annotators Apollo Google Web Toolkit (GWT) / BootstrapJBrowse DOJO / jQuery WebSocket JDBC File System Apollo Client(s) Server REST
  24. 24. ge nom e arc hite c t. org Apollo Server - Grails Security Architecture 24 Web Services Client Perl, Shell, Groovy, PHP, etc. Annotators Apollo Google Web Toolkit (GWT) / BootstrapJBrowse DOJO / jQuery WebSocket JDBC File System Apollo Server Client(s) REST
  25. 25. ge nom e arc hite c t. org Apollo Server - Grails Security Architecture 25 Web Services Client Perl, Shell, Groovy, PHP, etc. Annotators Apollo Google Web Toolkit (GWT) / BootstrapJBrowse DOJO / jQuery WebSocket JDBC File System Apollo Server Client(s) REST
  26. 26. ge nom e arc hite c t. org Apollo Server - Grails Security Architecture 26 Web Services Client Perl, Shell, Groovy, PHP, etc. Annotators Apollo Google Web Toolkit (GWT) / BootstrapJBrowse DOJO / jQuery WebSocket JDBC File System Apollo Client(s) Server REST
  27. 27. ge nom e arc hite c t. org Summary Annot ators Apollo Google Web Toolkit (GWT) / Bootstrap Apollo Google Web Toolkit (GWT) / Bootstrap Apollo Google Web Toolkit (GWT) / Bootstrap Real-time collaborative Curators refine genome annotations Integrates within workflow Visual evidence and feedback
  28. 28. ge nom e arc hite c t. org * Coordinate Transformation Future Work: Coordinate Transform 28 Mavenize Web Apollo Desktop Apollo DB backend, Sidebar, Grails, Multi- organism, WS 1.0 2.0 2.1 2.2 * Variant annotation and visualization 2.3 Genome Folding Phenotype annotation Assembly Composition Group 20 Group 31
  29. 29. ge nom e arc hite c t. org Combine Scaffolds Lock and Orient Combined Scaffolds Used Scaffolds Set Orientation Select to Combine Drag to Rearrange
  30. 30. ge nom e arc hite c t. org Combine Scaffolds View Individual Features
  31. 31. ge nom e arc hite c t. org Variant Annotation and Visualization Mavenize Web Apollo Desktop Apollo DB backend, Sidebar, Grails, Multi- organism, WS 1.0 2.0 2.1 2.2 2.3 Annotate Variants Phenotype annotation Visual Predictions * Coordinate Transformation * Variant annotation and visualization Create from Evidence (e.g., VCF)
  32. 32. • Berkeley Bioinformatics Open-source Projects (BBOP), Berkeley Lab: Apollo and Gene Ontology teams. Suzanna E. Lewis (PI). • § Christine G. Elsik (PI). University of Missouri. • * Ian Holmes (PI). University of California Berkeley. • Stephen Ficklin, GenSAS, Washington State University • Apollo is supported by NIH grants 5R01GM080203 from NIGMS, and 5R01HG004483 from NHGRI. Also supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231 • Alex Wild at http://www.alexanderwild.com/: leaf cutter ant, ensign wasp; Leo Bukeboom: Nasonia vitripennis jewel wasp; Wikimedia Commons: Apis mellifera honey bee; Mike MacNeil USDA/ARS • Thanks to you and the Apollo / GMOD Communities Apollo *Nathan Dunn Monica Munoz-Torres Deepak Unni § Colin Diesh § JBrowse Eric Yao Texas A&M University Eric Rasche Gene Ontology Chris Mungall Seth Carbon Jeremy Nguyen BBOP Apollo: http://genomearchitect.org https://github.org/GMOD/Apollo/ Questions? NAL at USDA Christopher Childers Monica Poelchau Yu-Yu “Fish” Lin @apollo_bbop
  33. 33. Extra Slides

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