1. CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Local Alignments

2. CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 After chaining

3. CS273a Lecture 10, Aut 08, Batzoglou Chaining local alignments 1.Find local alignments 2.Chain -O(NlogN) L.I.S. 3.Restricted DP

4. 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 p x, p y, to generate a new alignment with associated profile p result 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

5. 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 p x, p y, to generate a new alignment with associated profile p result 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, -) p x = (0.8, 0.2, 0, 0, 0) p y = (0.6, 0, 0, 0, 0.4) s(p x, p y ) = 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: p xy = (0.7, 0.1, 0, 0, 0.2) s(p x, -) = 0.8*1.0*s(A, -) + 0.2*1.0*s(C, -) Result: p x- = (0.4, 0.1, 0, 0, 0.5)

6. CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Threaded Blockset Aligner Human–Cow HMR – CD Restricted Area Profile Alignment

7. CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Reconstructing the Ancestral Mammalian Genome Human: C Baboon: C Cat: C Dog: G C C or G G

8. CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Neutral Substitution Rates