791_my_lecture3

# 791_my_lecture3 - 7.91 Lecture#3 Michael Yaffe More...

This preview shows pages 1–12. Sign up to view the full content.

7.9 1 – Lecture #3 More Multiple Sequence Alignment -and- Motif Scanning, Database Searching Michael Yaffe

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
Outline Multiple Sequence Alignment - Carillo & Lipman, Clustal(W) Position-Specific Scoring Matrices (PSSM) Information content, Shannon entropy Sequence logos Hidden Markov Models …Other approaches: Genetic algorithms, expectation maximization, MEME,Gibbs sampler FASTA, Blast searching, Smith-Waterman Psi-Blast Reading - Mount p. 139-150, 152-157, 161-171, 185-198
Multiple Sequence Alignments Sequences are aligned so as to bring the greatest number of single characters into register. If we include gaps, mismatches, then even dynamic programming becomes limited to ~ 3 sequences unless they are very short….need an alternative approach… Why?

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
Consider the 2 sequence comparison …..an O(mn) problem – order n 2 i =0 1 2 3 4 5 j = Gap V D S C Y 0 0 4 -8 -4 -3 -8 -16 -24 -32 -40 -8 1 -8 4 -12 -20 -28 -1 2 -16 -6 -9 7 -17 2 1 -7 3 -24 -14 3 -6 9 4 -32 -22 -14 -30 3 0 5 -40 -22 -7 1 3 13 6 -48 -38 -30 -15 5 23
For 3 sequences…. ARDFSHGLLENKLLGCDSMRWE .::. .:::. .:::: :::. GRDYKMALLEQWILGCD-MRWD .::. ::.: .. :. .::: SRDW--ALIEDCMV-CNFFRWD An O(mnj) problem ! Consider sequences each 300 amino acids Uh Oh !!! 2 sequences – (300) 2 Our polynomail problem 3 sequences – (300) 3 Just became exponential! but for v sequences – (300) v

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
Consider pairwise alignments between 3 sequences Carillo and Lipman – Sum of Pairs method Sequence B C e c n u q S A-C A-B B-C A-B-C Do we need to Score each node? Sequence A Get the multiple alignment score within the cubic lattice by Adding together the scores of the pairwise alignments…
In practice, doesn’t give optimal alignment…But we’re close! Seems reasonable that the optimal alignment won’t be far from the diagonal we were on…so we just set bounds on the location of the msa within the cube based on each pairwise-alignment. Then just do dynamic programing within the volume defined by the pre-imposed bounds

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
Still takes too long for more than three sequences…need a better way! Progressive Methods of Multiple Sequence Alignment Concept – simple: 1-Use DP to build pairwise alignments of most closely related sequences 2- Then progressively add less related sequences or groups of sequences…

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
ClustalW Higgins and Sharp 1988 •1 - Do pairwise analysis of all the sequences (you choose similarity matrix). 2- Use the alignment scores to make a phylogenetic tree. 3- Align the sequences to each other guided by the phylogenetic relationships in the tree. New features: Clustal ClustalW (allows weights) ClustalX (GUI-based Weighting is important to avoid biasing an alignment by many sequence Members that are closely related to each other evolutionarily!
Pairwise Alignment Steps in Multiple Alignment Multiple alignment following the tree from A S 1 S 1 S 1 6 pairwise comparisons then cluster analysis similarity align most similar pair Gaps to optimize alignment

This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document
This is the end of the preview. Sign up to access the rest of the document.

## This note was uploaded on 11/11/2011 for the course BIO 20.410j taught by Professor Rogerd.kamm during the Spring '03 term at MIT.

### Page1 / 65

791_my_lecture3 - 7.91 Lecture#3 Michael Yaffe More...

This preview shows document pages 1 - 12. Sign up to view the full document.

View Full Document
Ask a homework question - tutors are online