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129_Lecture5_2014

129_Lecture5_2014 - Sequence Analysis Sequence Analysis...

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1/28/14 1 Sequence Analysis Sequence Analysis: Outline 1. Why do we compare sequences? 2. Sequence comparison: from qualitative to quantitative methods 3. Deterministic methods: Dynamic programming 4. Heuristic methods: BLAST 5. Multiple Sequence Alignment Sequence Analysis 1. Why do we compare sequences? 1. Biological sequences 2. Homology vs analogy 3. Homology: orthology and paralogy 4. Applications 2. Sequence comparison: from qualitative to quantitative methods 3. Deterministic methods: Dynamic programming 4. Heuristic methods: BLAST 5. Multiple Sequence Alignment
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1/28/14 2 Similarity: Homology vs Analogy Homology: Similarity in characteris3cs resul3ng from shared ancestry. Analogy: The similarity of characteris3cs between two species that are not closely related; a>ributable to convergent evolu3on. Two sisters: homologs Two Elvis : analogs http://evolution.berkeley.edu/evolibrary/search/topicbrowse2.php?topic_id=55 Useful link: Similarity: Homology vs Analogy Classical example of homology: Legs and Limbs Koonin EV (2005). Orthologs, paralogs, and evolutionary genomics . Annu. Rev. Genet. 39:309-338. Further reading: Homologous sequences are orthologous if they were separated by a specia<on event Orthology: Homologous sequences are paralogous if they were separated by a gene duplica<on event Paralogy: Similarity in characteris<cs resul<ng from shared ancestry. Homology: Homology: Orthologs and Paralogs
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1/28/14 3 Homology: Orthologs and Paralogs Sequencing projects, assembly of sequence data Evolu<onary history Iden<fica<on of func<onal elements in sequences gene predic<on Classifica<on of proteins Compara<ve genomics RNA structure predic<on Protein structure predic<on Health Informa<cs Applica<ons of Sequence Analysis Sequence Analysis 1. Why do we compare sequences? 2. Sequence comparison: from qualitative to quantitative methods 1. Sequence composition 2. Sequence comparison: DotPlot 3. Sequence alignment 3. Deterministic methods: Dynamic programming 4. Heuristic methods: BLAST 5. Multiple Sequence Alignment
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1/28/14 4 DNA sequence: Chargaff s rules Rule 1: In double stranded DNA, the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine (basis of Watson Crick base pairing) Rule 2: the composition of DNA varies from one species to another; in particular in the relative amounts of A, G, T, and C bases DNA sequence: Chargaff s rules Comparing sequences based on their tri-peptide content Proteins: Structure, Function and Genetics 54 , 20-40 (2004)
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1/28/14 5 DotPlot: Overview of Sequence Similarity Build a table S: - rows: Sequence 1 - columns: Sequence 2 Assign a score S(i,j) to each entry in the table: - select a window size WS WS WS i j - Compare window around i with window around j -> Score(i,j) Display table of scores S - show a dot at position (i,j) if Score(i,j) > Threshold The Scoring Scheme Scores are usually stored in a weight matrix also called subs6tu6on matrix or matching matrix.
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