Genome Browser
Deepak Purushotham
Hamid Reza Hassanzadeh
Haozheng Tian
Juliette Zerick
The Plot
Lavanya Rishishwar
Piyush Ranjan
Lu Wang

The Outline
• The Need & The Requirement
• The Options
• The Chosen One
• The New Age

Why one should develop a Genome Browser
THE NEED

Why A Genome Browser?
I want to analyze this organism

Why A Genome Browser?
I want to analyze this organism
Metabolic
Pathways

What is expected out of a Genome Browser
THE REQUIREMENT

A Genome Browser?
I want something manageable

A Genome Browser!

The Genome Browser
“Genome browsers facilitate genomic analysis by presenting alignment, experimental and annotation data in the context of genomic
DNA sequences.”
Melissa S Cline & James W Kent, 2009
Genome browsers aggregate data
Taken From Andy Conley’s slides without permission

A Short Survey of the available Genome Browsers Modules
THE OPTIONS

A Brief Time Travel
• FlyBase, SGD, MGD, and WormBase
• Setting up an MOD is expensive and time-consuming.
• The four MODs agreed in the fall of 2000 to pool their resources and to make reusable components available to the community free of charge under an open source license.
• The goal of this NIH-funded project, christened GMOD, is
“…to generate a model organism database construction set that would allow a new model organism to be assembled by mixing and matching
various components.”

GMOD

Who uses GMOD?

GMOD Components

Visualization - GBrowse

Visualization

JBrowse

GBrowse Synteny

CMAP

DATA MANAGEMENT

Chado

Tripal
( http://www.cacaogenomedb.org/ )

TableEdit

BioMart

InterMine

ANNOTATION

MAKER

DIYA

Galaxy

Ergatis

Apollo

REALLY EXCITING OPTION!

JBrowse
• Smooth, fast navigation
(think Google Maps for genomes  )

JBrowse
• Smooth, fast navigation
(think Google Maps for genomes  )
• Supports BED, GFF, Bio::DB::*, Chado, WIG, BAM, UCSC
(intron/exon structure, name lookups, quantitative plots)
• Relies on pre-indexing to minimize security exposure and runtime bandwidth/CPU load on the server (future versions more likely to do some server work at runtime)
• Has an API for customized track/glyph extensions
• Is stably funded by NHGRI, with many interesting innovations implemented & pending integration

Smoother UI

Most Genome browsers

How is JBrowse different?

First look: Live Demo
A couple of JBrowses around the web
• http://intron.ccam.uchc.edu/JBrowse/Dmel/
• http://jbrowse.org/ucsc/hg19/

Types of Tracks

Pros
• Fast and smooth!
• User Friendly
• Works nicely on an iPad/iPhone too

Cons
• No user-uploaded data support
• Slow for big numbers of reference seqs (e.g.
5,000 annotated contigs)
• Few glyph options, feature tracks are limited by the facts of <div>

What to pick?

Fancy concept
?
Tried and tested

Gbrowse and its Features
THE CHOSEN ONE

GBrowse
• Most popular web based genome browser
• Visualize genome features along a reference sequence
• Open Source
• Highly customizable
• Excellent usability
• Rich set of “glyphs”
– Genome features
– Quantitative Data
– Sequence Alignments

Header
GBrowse
Main Browser Window
Track Menu

Under The Hood
• Client-Server
Architecture
• GBrowse Architecture
• Installation Issues
• Input Data
• Configuration File
• Customization

Client Server Architecture
1. The user types in the URL: browser2012.biology.gatech.edu

Client Server Architecture
2. Browser interprets and sends the request to HTTP Server

Client Server Architecture
3. Web Server receives the request and
“serves” the client i.e., starts Gbrowse

Client Server Architecture
4. In case of success, relevant hypertexts and multimedia is generated by accessing the database

Client Server Architecture
5. The output traverses the same path back

Client Server Architecture
5. The output traverses the same path back

Client Server Architecture
6. The whole process repeats again when the user interacts with the browser

How you see what you see
Juxtaposed Images

How are so many images generated?

How you see what you see
+ Hyper Text files

How you see what you see
Multimedia files + Hyper Text

GBrowse Architecture
Stein L D et al. Genome Res. 2002;12:1599-1610
©2002 by Cold Spring Harbor Laboratory Press

The Bio::DB::SeqFeature database Schema

Name
Attribute n n
1
Attribute List
1
1
Parent2Child n n
1
Feature
1
Type List n n
Location List
1

Data file (.gff3)
Reference
Sequence
(Chr/Clone
/Contig)
Source
Eg:
Prodigal/
Glimmer
Type
(sequence ontology
(SO) terms)
Strand Attributes
Format: tag=value
Start
End
Score
Eg: Evalue
Phase
(0/1/2)

Attributes (Data file)
Different tags have predefined meanings:
• ID: Gives the feature a unique identifier. Useful when grouping features together (such as all the exons in a transcript).
• Name: Display name for the feature. This is the name to be displayed to the user.
• Alias: A secondary name for the feature. It is suggested that this tag be used whenever a secondary identifier for the feature is needed, such as locus names and accession numbers.
• Note: A descriptive note to be attached to the feature. This will be displayed as the feature's description.
Alias and Note fields can have multiple values separated by commas. For example : Alias=M19211,gna-12,GAMMA-GLOBULIN
• Other good stuff can go into the attributes field.

Gbrowse Configuration File
• Global Website Settings
• Additional HTML Pages
• JavaScript
• Jquery
• Global Database
Settings
• Data Source Definitions

Customizations

Configuration file (.conf)

Making a new Track
### TRACK CONFIGURATION ###
[ExampleFeatures] feature = remark glyph = generic stranded = 1 bgcolor = orange height = 10 key = Example Features

Data:
Adding Multiple Tracks
Configuration:
Searchable
Links
Result UI:
Popup balloons with links

Searching for Features click
Gene symbols
Gene IDs
Sequence IDs
Genetic markers
Relative nucleotide coordinates
Absolute nucleotide coordinates etc...

Viewing Multiple Tracks
Low Magnification

Viewing Multiple Tracks
High Magnification

In short…
• Main features (Determination of protein coding and non-coding,…)
• Quantitative data (E-value, Identity percentage)
• Other evidences (Interpro, CoGs, etc.)
• GC content and other useful measurements
• Protein and DNA sequences

Value-Added Additions
THE NEW AGE

What’s New
RICHER ANNOTATION

Richer Annotation
INCREASED ANNOTATION INFO

3000
2500
2000
1500
Total Genes
Pangenome Hits
UniProt
1000
500
0
M19107 M19501 M21127 M21621 M21639 M21709

Richer Annotation
INTEGRATED QUALITY SCORE

Origin of Database Matches
Color code was used for matches originated from different databases

Quality Value Integration
It distinguishes between different databases…
However, for matches from the same database…

Quality Scores
Color code will also be used for matches with different quality…

Different E-values shown with different shades of colors

What’s New
MORE LINK-OUTS

COGs
KEGG ID

What’s New
PATHWAYS

KEGG
Genes
KEGG ID
KEGG
Compound
KEGG
Pathway

Synthesis!
ORGANISM SPECIFIC PAGES

Organism Summary Page
• At this point of the course, we have gathered a lot of information for the strains we are dealing with
• Not all of this information could be represented inside the genome browser
• We propose a separate section in the browser containing strain-wise summarized information

Organism Summary Page
• Conceptually, the page could contain:
– Biological information
– Assembly information:
Genome Size, Number of contigs, N50, Sequencing platform
– Gene Prediction information:
Number of protein coding and non-protein coding genes, links to 16s rRNA gene
– Annotation information:
Percent annotation, function distribution pie
– Comparative information:
Unique protein clusters, etc.

Organism Summary Page

Adding more values
OPERONS

Operons
• Operon
“…is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter”
• ~70% of the genes have been assigned a unique
OperonID
• OperonID will provide an additional browsing mechanism for biologist connecting co-
transcribed and co-regulated genes.

Operons

Incorporating Operon Information

More with Comparison
BRIG PATTERN

BRIG Patterns
• Concept:
To either generate BRIG images at run time or load static images when the user requests for BRIG Pattern between two species

BRIG Patterns

• Questions?
• Comments?
• Concerns?
That’s All Folks!
• If you have any suggestions, we would love to hear from you! (There is a page on Wiki for it!)