129_Lecture5_2014 - Sequence Analysis Sequence Analysis...

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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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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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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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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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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.