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Introduction To Bioinformatics Tutorial 2. Local Alignment Tutorial 2.

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Presentation on theme: "Introduction To Bioinformatics Tutorial 2. Local Alignment Tutorial 2."— Presentation transcript:

1 Introduction To Bioinformatics Tutorial 2

2 Local Alignment Tutorial 2

3 Usage: Spelling,.. Different Types: –Hamming –Levenshtein Algorithm –Naïve solution –Dynamic programming Edit Distance

4 Richard Bellman (1940) “Program” –Computer program? –Optimal Schedule Dynamic Programming

5 Conditions –Division to sub-problems possible –(Optimal) Sub-problem solution usable (many times?) –“Bottom-up” approach Dynamic Programming

6 Examples –Shortest path –Fibonacci Dynamic Programming

7 Usage: Spelling, Biology,… Compare sequences Similar sequence  Ancestral origin Function … Edit Distance

8 Dynamic Programming algorithm for finding local matches between two sequences. What is a local match?: –It is a best-matching, highest-scoring region between two sequences. –It is a well conserved region between two sequences. Local Alignment

9 Alignment NnNn N1N1 M1M1 MmMm

10 NnNn N1N1 M1M1 MmMm [I,J] Best alignment M 1..I, N 1..J

11 Alignment All possible alignments encoded as path in matrix

12 The differences: 1.We can start a new match instead of extending a previous alignment. 2.Instead of looking only at the far corner, we look anywhere in the table for the best score Global vs Local Global Local Scoring System Match : +1 Mismatch: -2 Indel : -1

13 Local Alignment Scoring System –Match : +1N i =M j –Mismatch: -1N i =M j –Indel : -2 NnNn N1N1 M1M1 MmMm

14 Local Alignment Scoring System –Match : +1N i =M j –Mismatch : -1N i =M j –Indel : -2 NnNn N1N1 M1M1 MmMm

15 Local Alignment Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 NnNn N1N1 M1M1 MmMm

16 Local Alignment Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 NnNn N1N1 M1M1 MmMm N1-N1-

17 Local Alignment Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 NnNn N1N1 M1M1 MmMm -M1-M1

18 Local Alignment Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 NnNn N2N2 N1N1 M1M1 M2M2 MmMm N1 -.. M1M2..

19 Local Alignment Fill: 1.We fill the table like in global alignment, but we don’t allow negative numbers (turn every negative number to 0) 2.No arrows coming out from cells with a 0. Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 +1 if M 2 =N 2 ; -1 if M 2 =N 2 -2 NnNn N2N2 N1N1 M1M1 M2M2 MmMm N 1 N 2.. M 1 M 2.. N 1 -.. M 1 M 2.. N 1 N 2.. M 1 -..

20 Local Alignment Trace: We trace back from the highest scoring cells. +1 if M 2 =N 2 ; -1 if M 2 =N 2 -2 NnNn N2N2 N1N1 M1M1 M2M2 MmMm N 1 N 2.. M 1 M 2.. N 1 -.. M 1 M 2.. N 1 N 2.. M 1 -..

21 Local Alignment Question: Will there be gaps at the start/end? NnNn N2N2 N1N1 M1M1 M2M2 MmMm

22 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0 T 1 A 2 A 3 T 4 A 5

23 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 A 2 A 3 T 4 A 5

24 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 0 A 2 0 A 3 0 T 4 0 A 5 0

25 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 0 A 2 0 A 3 0 T 4 0 A 5 0 -T-T

26 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 0 A 2 0 A 3 0 T 4 0 A 5 0 T-T-

27 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 0? A 2 0 A 3 0 T 4 0 A 5 0

28 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 0? A 2 0 A 3 0 T 4 0 A 5 0 -T T- -T T- -T +1 -2

29 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 01 A 2 0 A 3 0 T 4 0 A 5 0

30 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 0000000 T 1 010 A 2 0 A 3 0 T 4 0 A 5 0

31 0 0T 4 0A 3 0A 2 0010010T 1 00000000 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

32 0A 5 0T 4 0A 3 1200200A 2 0010010T 1 00000000 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

33 0A 5 0T 4 3101100A 3 1200200A 2 0010010T 1 00000000 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

34 0A 5 1020010T 4 3101100A 3 1200200A 2 0010010T 1 00000000 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

35 1300200A 5 1020010T 4 3101100A 3 1200200A 2 0010010T 1 00000000 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

36 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 000000 010010 A 2 0020021 A 3 001101 3 T 4 0100201 A 5 00200 3 1

37 0 T1T1 A2A2 C3C3 T4T4 A5A5 A6A6 0 000000 T 1 010010 A 2 0020021 A 3 0011013 T 4 0100201 A 5 0020031 Leave only paths from highest score

38 TAA TACTA TAATA

39 And Now… Global Alignment 1.We keep negative numbers. 2.Arrows coming out from any cell. 3.We trace back from right-bottom to left-top of the table. Scoring System –Match : +1 –Mismatch: -1 –Indel : -2 +1 if M 2 =N 2 ; -1 if M 2 =N 2 -2 NnNn N2N2 N1N1 M1M1 M2M2 MmMm N 1 N 2.. M 1 M 2.. N 1 -.. M 1 M 2.. N 1 N 2.. M 1 -..

40 A 5 T 4 A 3 A 2 T 1 0 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10 Match: +1 Mismatch:-1 Indel: -2 -12-10-8-6-4-2 -10 -8 -6 -4 -2 0 -9-7-5-31 130-3-4-7 -202-2-5 -3 10-3 -6-4-202

41 A 5 T 4 A 3 A 2 T 1 0 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10 Match: +1 Mismatch:-1 Indel: -2 -12-10-8-6-4-2 -10 -8 -6 -4 -2 0 -9-7-5-31 130-3-4-7 -202-2-5 -3 10-3 -6-4-202

42 130-3-4-5A 5 02 -2 -4T 4 1 10-3 A 3 -20 02-2A 2 -6-4-2-31 T 1 -6-5-4-3-200 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10

43 TACTAA TAATA- TACTAA TAAT-A

44 A 5 T 4 A 3 A 2 T 1 0 A6A6 A5A5 T4T4 C3C3 A2A2 T1T10


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