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

Local Alignments

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

After chaining

CS273a Lecture 10, Aut 08, Batzoglou

Chaining local alignments

1. Find local alignments

2. Chain -O(NlogN) L.I.S.

3. Restricted DP

CS273a Lecture 10, Aut 08, Batzoglou

Progressive Alignment

• When evolutionary tree is known:

Align closest first, in the order of the tree In each step, align two sequences x, y, or profiles px, py, to generate a new

alignment with associated profile presult

Weighted version: Tree edges have weights, proportional to the divergence in that edge New profile is a weighted average of two old profiles

x

w

y

z

CS273a Lecture 10, Aut 08, Batzoglou

Progressive Alignment

• When evolutionary tree is known:

Align closest first, in the order of the tree In each step, align two sequences x, y, or profiles px, py, to generate a new

alignment with associated profile presult

Weighted version: Tree edges have weights, proportional to the divergence in that edge New profile is a weighted average of two old profiles

x

w

y

z

Example

Profile: (A, C, G, T, -)px = (0.8, 0.2, 0, 0, 0)py = (0.6, 0, 0, 0, 0.4)

s(px, py) = 0.8*0.6*s(A, A) + 0.2*0.6*s(C, A) + 0.8*0.4*s(A, -) + 0.2*0.4*s(C, -)

Result: pxy = (0.7, 0.1, 0, 0, 0.2)

s(px, -) = 0.8*1.0*s(A, -) + 0.2*1.0*s(C, -)

Result: px- = (0.4, 0.1, 0, 0, 0.5)

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

Threaded Blockset Aligner

Human–Cow

HMR – CDRestricted AreaProfile Alignment

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

Reconstructing the Ancestral Mammalian Genome

Human: C

Baboon: C

Cat: C

Dog: G

C

C or G

G

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

Neutral Substitution Rates