BRUDNO LAB: A WHIRLWIND TOUR Marc Fiume Department of Computer Science University of Toronto

1. what we do, our tools 2. Savant Genome Browser Outline Savant Genome Browser -

WHAT WE DO Savant Genome Browser -

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 Savant Genome Browser -

HTS Pipeline Savant Genome Browser -

What to do with all these reads? Savant Genome Browser -

1. Assembly Savant Genome Browser - ASSEMBLY: reconstruct the donor’s genome “HapSembler”: specialized for highly polymorphic species

2. Alignment Savant Genome Browser - 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 Savant Genome Browser - 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 Savant Genome Browser -

Our Bioinformatics Tools READ MAPPING (SHRiMP) SNP DETECTION (VARiD) SNP DETECTION (VARiD) INDEL DETECTION (MODiL) INDEL DETECTION (MODiL) CNV DETECTION (CNVer) CNV DETECTION (CNVer) ASSEMBLY (HapSembler) ASSEMBLY (HapSembler) VISUALIZATION (SAVANT) VISUALIZATION (SAVANT) COMPRESSION

SAVANT GENOME BROWSER Savant Genome Browser -

Genome Browsing, the old way Savant Genome Browser -

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 Savant Genome Browser -

Tools for HTS data analysis ToolCostComputationVisualization Read Alignment e.g. Bowtie, BWA FreeYN File Format Conversion e.g. Galaxy, SAMTools FreeYN Other Comand-line Tools e.g. Genetic Variation Discovery, Comparitive Genomics, etc. FreeYN UCSC Genome BrowserFreeNY Integrative Genomics ViewerFreeNY GBrowseFreeNY CLC Genomics Workbench$$$YY Savant Genome Browser - substantial disconnect between the processes of computational analysis and visualization

Tools for Genomic Data Analysis ToolCostComputationVisualization Read Alignment e.g. Bowtie, BWA FreeYN File Format Conversion e.g. Galaxy, SAMTools FreeYN Other Comand-line Tools e.g. Genetic Variation Discovery, Comparitive Genomics, etc. FreeYN UCSC Genome BrowserFreeNY Integrative Genomics ViewerFreeNY GBrowseFreeNY CLC Genomics Workbench$$$YY Savant Genome BrowserFreeYY Savant Genome Browser - substantial disconnect between the processes of computational analysis and visualization

ASIDE: Cytoscape? platform for visual analysis of networks extensive plugin framework Savant Genome Browser - Bader Lab

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

(Very) Short List of Features FASTA, BED, WIG, GFF, tab-delimited, BAM local and remote Data Format Support pack, squish for BED and GFF tracks mismatch, SNP, matepair modes for BAM tracks Alternative Visualization Modes very fast data access (<1s) small memory footprint (<250 MB) Speed and Interactivity sessions, bookmarking of interesting regions, track locking, data selection Extras ~ none, works on all major operating systems System Requirements Savant Genome Browser -

FEATURE DEMONSTRATION Savant Genome Browser - INTERFACE HTS READ ALIGNMENTS EXAMPLE PLUGIN: SNP FINDER

Power of visual analytics task: find the correct parameter for command-line tool Savant Genome Browser -

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.) Savant Genome Browser -

CONCLUSIONS Savant Genome Browser -

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 Savant Genome Browser -

Acknowledgements RecepAndrewVladMike Brudno YueMarc Vanessa Orion JoeNilgun Paul Vera MiskoYoni

Thanks! Savant Genome Browser -