CS273a Lecture 10, Aut 08, Batzoglou Multiple Sequence Alignment.

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273a Lecture 10, Aut 08, Batzoglou Multiple Sequence Alignment
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Transcript of CS273a Lecture 10, Aut 08, Batzoglou Multiple Sequence Alignment.

CS273a Lecture 10, Aut 08, Batzoglou

Multiple Sequence Alignment

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

Evolution at the DNA level

…ACGGTGCAGTTACCA…

…AC----CAGTCCACCA…

Mutation

SEQUENCE EDITS

REARRANGEMENTS

Deletion

InversionTranslocationDuplication

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

Orthology and Paralogy

HB HumanHB Human

WB WormWB Worm

HA1 HumanHA1 Human

HA2 HumanHA2 Human

YeastYeast

WA WormWA Worm

Orthologs:Derived by speciation

Paralogs:Everything else

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

Orthology, Paralogy, Inparalogs, Outparalogs

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

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

Genome Evolution – Macro Events

• Inversions• Deletions• Duplications

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

Synteny maps

Comparison of human and mouse

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

Synteny maps

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

Synteny maps

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

Synteny maps

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

Building synteny maps

Recommended local aligners• BLASTZ

Most accurate, especially for genes Chains local alignments

• WU-BLAST Good tradeoff of efficiency/sensitivity Best command-line options

• BLAT Fast, less sensitive Good for

• comparing very similar sequences • finding rough homology map

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

Index-based local alignment

Dictionary:

All words of length k (~10)

Alignment initiated between words of alignment score T

(typically T = k)

Alignment:

Ungapped extensions until score

below statistical threshold

Output:

All local alignments with score

> statistical threshold

……

……

query

DB

query

scan

Question: Using an idea from overlap detection, better way to find all local alignments between two genomes?

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

Local Alignments

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

After chaining