Methodologies for motif finding using Comparative Genomics : Strengths and Limitations

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Comparative Genomics in Vertebrates

• Amol Prakash, Martin Tompa
• Computer Science Engineering

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Talk Outline

• Introduction to gene regulation
• Comparative Genomics the big picture
• Analysis
• Our contribution
• Future Work

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Introduction
1. DNA
Gene
Upstream Sequence
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Introduction
1. DNA
Gene
Upstream Sequence

• Goal To identify all regulatory elements.
• Motifs putative regulatory regions

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Comparative Genomics

• geneA.human geneB.frog
• They have evolved from a common ancestor
• (geneA.fruman)

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Whole GenomeComparative Genomics

• Used in yeast
• Cliften et al. (2003), Kellis et al. (2003)
• Vertebrates ?
• Human/Chimp/Mouse/Rat
• Human/Chimp/Mouse/Rat/Chicken
• Human/Chimp/Mouse/Rat/Chicken/Fugu

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The BIG Picture

• Motif Finding Using Comparative Genomics
• Module 1 Module 2 Module
  3

Assemble homologous promoter sequences
Find conserved regions i.e. motifs
Validate motifs for their biological significance
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Module 1 Homologous promoter sequences

• Hazards
• Most annotations, homology predictions are highly
  error prone, especially distant species
• Current tools cannot differentiate wrong
  dataset from correct one.
• Methods
• Dataset filters to avoid the above problems

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Module 2 Search for motifs

• Hazards
• Most tools were not intended for this purpose
• Sensitivity/Specificity issues
• Method
• Likelihood based method
• to evaluate performance of the various tools
• to evaluate significance of a motif

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Module 3 Motif treasure

• Method
• A statistical clustering of similar motifs
• Result
• A high quality list of motifs, many of which are
  novel

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Future Work

• Short term goal publishing
• Long term goals
• Analyze not-so-highly conserved regions.
• Very long term goals
• Analyze more species
• Dog,cow should be available soon
• Increase datasize more homologous regions

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Acknowledgements

• Mathieu Blanchette
• Saurabh Sinha
• Larry Ruzzo
• Zasha Weinberg
• Zizhen Yao
• Nan Li

• Ensembl Helpdesk
• GS support staff