Brudno lab: A WHIRLWIND TOUR

BRUDNO LAB: A WHIRLWIND TOUR

Marc FiumeDepartment of Computer ScienceUniversity of Toronto

Savant Genome Browser - http://compbio.cs.toronto.edu/savant/

1. what we do, our tools2. Savant Genome Browser

Outline

WHAT WE DO



• main focus: genomic analysis using output from high-throughput sequencing (HTS) machines

• high throughput: sequence billions of nucleotides per week• poor data quality: “reads” are shorter; error profiles are poorly understood

What we do


HTS Pipeline


What to do with all these reads?


1. Assembly

• ASSEMBLY: • reconstruct the donor’s genome• “HapSembler”: specialized for highly polymorphic species


2. Alignment

ALIGNMENT• find region in a “reference” genome that matches closely with each read; suggests similar origin from “donor”

• “SHRiMP”: Short Read Mapping Package


3. Genetic Variation Discovery

GENETIC VARIATION DISCOVERY• find differences between two genomes• between donor and reference• between two samples (e.g. tumour vs. normal)

• “VARiD”, “MODiL”, and “CNVer”


Genetic Variation• Single Nucleotide Polymorphism (SNP): genomes have different nucleotides at corresponding positions• VARiD – VARiation IDentification

• Insertions and Deletions (Indels): genomes have additional sequence put in or sequence taken out at corresponding locations• MODiL – Mixtures of Distributions Indel Locator

• Copy Number Variation (CNV): genomes have a different number of the same sequence• CNVer

Our Bioinformatics Tools

READ MAPPING (SHRiMP)

SNP DETECTION(VARiD)

INDEL DETECTION(MODiL)

CNV DETECTION(CNVer)

ASSEMBLY(HapSembler)

VISUALIZATION(SAVANT)

COMPRESSION

SAVANT GENOME BROWSER



Genome Browsing, the old way


Challenge presented by HTS datasets• genomic data is generated in high volumes• HTS machines generate billions of bases per run

• interpretation and analysis challenge• typical pipeline employs many separate tools for computation and visualization


Tools for HTS data analysisTool Cost Computation Visualization

Read Alignment e.g. Bowtie, BWA

Free Y N

File Format Conversion e.g. Galaxy, SAMTools

Free Y N

Other Comand-line Toolse.g. Genetic Variation Discovery, Comparitive Genomics, etc.

Free Y N

UCSC Genome Browser Free N Y

Integrative Genomics Viewer Free N Y

GBrowse Free N Y

CLC Genomics Workbench $$$ Y Y

• substantial disconnect between the processes of computational analysis and visualization


Tools for Genomic Data AnalysisTool Cost Computation Visualization

Read Alignment e.g. Bowtie, BWA

Free Y N

File Format Conversion e.g. Galaxy, SAMTools

Free Y N

Other Comand-line Toolse.g. Genetic Variation Discovery, Comparitive Genomics, etc.

Free Y N

UCSC Genome Browser Free N Y

Integrative Genomics Viewer Free N Y

GBrowse Free N Y

CLC Genomics Workbench $$$ Y Y

Savant Genome Browser Free Y Y

• substantial disconnect between the processes of computational analysis and visualization


ASIDE: Cytoscape?

• platform for visual analysis of networks• extensive plugin framework

Bader Lab


Savant Genome Browser• platform for integrated visual analysis of genomic data• feature-rich genome browser• computationally extensible via plugin framework

FEATURE DEMONSTRATION


INTERFACEHTS READ ALIGNMENTSEXAMPLE PLUGIN: SNP FINDER


Power of visual analytics• task: find the correct parameter for command-line tool


Plugin Framework• unlocks the potential for performing visual analytics

• beneficial for both users and tool developers

• tool developers: simple platform for development and dissemination of work• plugin development is easy• API contains over a hundred prebuilt functions (e.g. get

track data, add bookmarks, draw custom graphics, etc.)

CONCLUSIONS



Conclusions• Savant is a platform for integrated visualization and analysis of genomic data

• stand-alone genome browser• novel features: e.g. table view, visualization modes,

data selection, etc.

• computationally extensible through plugin framework

• makes interpretation and analysis of genomic data easier and more efficient

Acknowledgements

Recep Andrew Vlad MikeBrudno

Yue Marc

Vanessa OrionJoe Nilgun

Paul

Vera

Misko Yoni


Thanks!

Brudno lab: A WHIRLWIND TOUR

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