CS273a Lecture 14, Fall 08, Batzoglou CS273a Lecture 14, Fall 2008 Finding Conserved Elements (1) Binomial method 25-bp window in the human genome

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, 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

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, 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

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Finding Conserved Elements

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Finding Conserved Elements (3)

GERP

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Phylo HMMs

HMM

Phylogenetic Tree Model

Phylo HMM

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Finding Conserved Elements (3)

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

How do the methods agree/disagree?

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Statistical Power to Detect Constraint

L

N

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

CS273a Lecture 14, Fall 08, BatzoglouCS273a Lecture 14, Fall 2008

Statistical Power to Detect Constraint

L

N

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