CS273a Lecture 10, Aut 08, Batzoglou Multiple Sequence Alignment

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Evolution at the DNA level …ACGGTGCAGTTACCA… …AC----CAGTCCACCA… Mutation SEQUENCE EDITS REARRANGEMENTS Deletion Inversion Translocation Duplication

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Orthology and Paralogy HB Human WB Worm HA1 Human HA2 Human Yeast WA Worm Orthologs: Derived by speciation Paralogs: Everything else Orthologs: Derived by speciation Paralogs: Everything else

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Orthology, Paralogy, Inparalogs, Outparalogs

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

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Genome Evolution – Macro Events Inversions Deletions Duplications

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Synteny maps Comparison of human and mouse

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Synteny maps

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Synteny maps

CS273a Lecture 10, Aut 08, Batzoglou CS273a Lecture 10, Fall 2008 Synteny maps

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

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