neutral substitution rates

10
273a Lecture 10, Aut 08, Batzoglou 273a Lecture 10, Fall 2008 Neutral Substitution Rates

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Neutral Substitution Rates. Finding Conserved Elements (1). Binomial method 25-bp window in the human genome Binomial distribution of k matches in N bases given the neutral probability of substitution. Finding Conserved Elements (2). A. C. Parsimony Method - PowerPoint PPT Presentation

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Page 1: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Neutral Substitution Rates

Page 2: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Finding Conserved Elements (1)

• Binomial method 25-bp window in the human genome Binomial distribution of k matches in N bases given the neutral

probability of substitution

Page 3: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Finding Conserved Elements (2)

• Parsimony Method Count minimum # of mutations explaining each column Assign a probability to this parsimony score given neutral model Multiply probabilities across 25-bp window of human genome

A

CAAG

Page 4: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Finding Conserved Elements

Page 5: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Finding Conserved Elements (3)

GERP

Page 6: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Phylo HMMs

HMM

Phylogenetic Tree Model

Phylo HMM

Page 7: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Finding Conserved Elements (3)

Page 8: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

How do the methods agree/disagree?

Page 9: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Statistical Power to Detect Constraint

L

N

C: cutoff # mutationsD: neutral mutation rate: constraint mutation rate relative to neutral

Page 10: Neutral Substitution Rates

CS273a Lecture 10, Aut 08, BatzoglouCS273a Lecture 10, Fall 2008

Statistical Power to Detect Constraint

L

N

C: cutoff # mutationsD: neutral mutation rate: constraint mutation rate relative to neutral