Journal club

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• Journal club
• 06/27/08

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Phylogenetic footprinting

• A technique used to identify TFBS within a
  non-coding region of DNA of interest by comparing
  it to the orthologous sequences in different
  species (1988 by Tagle)
• The function and DNA binding preferences of
  transcription factors are well-conserved between
  diverse species
• Important non-coding DNA sequences that are
  essential for regulating gene expression will
  show differential selective pressure. (A slower
  rate of change occurs in TFBS than in other parts
  of the non-coding genome)

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Phylogenetic footprinting
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Phylogenetic footprinting

• Not all conserved sequences are under selection
  pressure
• To eliminate false positives, statistical
  analysis must be performed that the motifs
  reported have a mutation rate meaningfully less
  than that of the surrounding nonfunctional
  sequence.

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Mixture selective pressure

• Maintain the function of the protein encoded by
  the gene (AA selecvtive pressure)
• Maintain their regulatory role (CRUNCS) ex
  regulatory factors binding sites

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Methods

• Sequence conservation
• Entropy score
• Parsimony score
• Conservation p-value (mixture models)
• Posterior distributions of conservation scores
• Conditional p-values

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Parsimony V.S. Entropy Score
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Fitchs algorithm
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How surprising?
1. Conditional model
Aligned codons illustrating to what extent the
conservation of each column is surprising, given
the amino acids encoded
L CUN, UUA, UUG W UUG V GUN AGCN GGGN
D GAU, GAC
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1. Conditional model
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2. Mixture model
50 functional classes
Hydrophobic favor
Glycine favor
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2. Mixture model
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Non-coding model HKY model
represents the transition/transversion rate ratio
for
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How to compute
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