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GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

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Page 1: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GMOD/GBrowse_syn

Sheldon McKayReactomeOntario Institute for Cancer Research

Page 2: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

A few words on whole genome alignment

A brief survey of synteny browsers

A few challenges of rendering comparative data

Comparative genome browsing with GBrowse_syn

Outline

Page 3: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Hierarchical Genome Alignment Strategy

Mask repeats (RepeatMasker, Tandem Repeats Finder, nmerge, etc

Identify orthologous regions (ENREDO, MERCATOR, orthocluster, etc)

Nucleotide-level alignment (PECAN, MAVID, etc)

Further processing

GBrowse_syn

GBrowse_syn

GBrowse

Raw genomic sequences

Page 4: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research
Page 5: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research
Page 6: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research
Page 7: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

A Few Use Cases

Multiple sequence alignment data from whole genomes

Synteny or co-linearity data without alignments

Gene orthology assignments based on proteins

Self vs. Self comparison of duplications, homeologous regions, etc

Others

Page 8: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

What is a Synteny Browser?

- Has display elements in common with genome browsers

- Uses sequence alignments, orthology or co-linearity data to highlight different genomes, strains, etc.

- Usually displays co-linearity relative to a reference genome.

Page 9: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GBrowse_syn

• Does not rely on perfect co-linearity across the entire displayed region (no orphan alignments)

• Offers “on the fly” alignment chaining• No upward limit on the number of species• Used grid lines to trace fine-scale indels (sequence

insertion/deletions)• Integration with GBrowse data sources• Ongoing support and development

Page 10: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GBrowse-like interface

Page 11: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GBrowse Databases*

*.synor

*.conf

*.synconf

GBrowse_synalignment database

GBrowse_syn

Species config. Master config.

Page 12: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

GBrowse_syn Architecture[GBrowse]

[GBrowse] [GBrowse]

[GBrowse]

Page 13: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Getting Data into GBrowse_syn

CLUSTALW PECANMSF ad hoc tab-delimitedFASTA STOCKHOLM GFF3 etc…

Loading scripts

Page 14: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research
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Optional “All in one” view

Page 18: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Adding markup to the annotations

Page 19: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Problem : How to use Insertions/Deletion data

Page 20: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Tracking Indels with grid lines

Page 21: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Evolution of Gene Structure

Page 22: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Putative gene or loss

Page 23: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Comparing gene models

Page 24: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Comparing assemblies

Not bad

Needs work

Page 25: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Example Mercator Alignment

Page 26: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Getting the most out of small aligned regions or orthology-only data

Page 27: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Gene Orthology

Chained Orthologs

Page 28: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

2 panels mergedInversion + translocation?

Page 29: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Pecan alignments

Protein orthology based Synteny blocks

Page 30: GMOD/GBrowse_syn Sheldon McKay Reactome Ontario Institute for Cancer Research

Duplications