1. Protein multiple sequence alignment by hybrid bio-inspired algorithms Vincenzo Cutello, Giuseppe Nicosia*, Mario Pavone and Igor Prizzi Nucleic Acids Research, 2011 D00922025 黃任鋒 R00922102 張庭耀 R00922156 陳子筠 R99922158 蘇宏麒 1

2. Outline Introduction & background IMSA Cloning and hypermutation operators Results Conclusion

3. Introduction and Background D00922025 黃任鋒 3

4. About this paper 4

5. Problem of MSA 5

6. Methods for MSA 6

7. Progressive alignments 7

8. Exact algorithms 8

9. Survey of MSA 9

10. Outline Introduction & background IMSA Cloning and hypermutation operators Results Conclusion

11. Immunological Multiple Sequence Alignment(IMSA) R00922102 張庭耀 11

12. IMSA Two different strategies to create the initial population New hypermutation operators - solving protein MSA that insert or remove gaps Gap columns, which have been matched, are moved to the end of the sequence The remaining elements(i.e. amino acids) and existing gaps are shifted into the freed space 12

13. IMSA Considers antigens (Ags) and B cells - Ag is a given MSA instance, i.e. the protein sequences to align - B cells are a population of alignments that have solved(or approximated) the initial problem 13

14. 14

15. 15

16. Initial population strategies 16

17. Random_initialization 17

18. Random_initialization 18

19. CLUSTALW-seeding 19

20. Outline Introduction & background IMSA Cloning and hypermutation operators Results Conclusion

21. IMSA-Cloning and hypermutation operators R00922156 陳子筠 21

22. Cloning and hypermutation operators 22 Represented by “Static cloning operators” Clones B cells dup times P (clo) of N c = d * dup B cells, d is population size

23. Cloning and hypermutation operators 23

24. InsGap 24

25. 25 InsGap P (gap)

26. 26 RemGap P (gap)

27. BlockShuffling operator Select randomly start point in a sequence BlockMove BlockSplitHor BlockSplitVer 27

28. 28 BlockMove P (block)

29. 29 BlockSplitHor P (block)

30. 30 BlockSplitVer P (block)

31. STRIP_GAPS 31

32. Aging operator 32 Eliminates old B cells in populations P (t), P (gap) and P (block) The generation number of B cell is τ B New population P (t+1) of d B cells selected best survivors by (μ+λ) - selection

33. 33

34. Outline Introduction & background IMSA Cloning and hypermutation operators Results Conclusion

35. Results R99922158 蘇宏麒 35

36. Classical Benchmark BAliBASE version 1.0, 2.0 and 3.0 - A benchmark alignment database. - The evaluation of multiple sequence alignment. 36

37. BAliBASE version 1.0 141 reference alignments 5 reference sets 37

38. BAliBASE version 1.0, cont. Reference 1: equi-distant sequences with various levels of conservation Reference 2: family aligned with a highly divergent “orphan” sequence Reference 3: subgroups with < 25% residue identity between groups Reference 4: sequences with N/C-terminal extensions Reference 5: internal insertion 38

39. BAliBASE version 2.0 Include all alignments in version 1.0 Alignments are verified and corrected 39

40. BAliBASE version 3.0 same as version 2.0 contains 218 alignments 40

41. IMSA - reference 1 lad2 41

42. IMSA - reference 1 laym3 42

43. IMSA - reference 1 1hfh 43

44. IMSA - reference 1 2mhr 44

45. IMSA - Reference 3 luky 45

46. IMSA - Reference 5 1qpg 46

47. IMSA - BAliBASE 1.0 47

48. IMSA vs CLUSTALW-seeding - BAliBASE 1.0 48

49. IMSA - BAliBASE 2.0 49

50. IMSA vs CLUSTALW-seeding - BAliBASE 2.0 50

51. IMSA vs AIS - BAliBASE 2.0 51

52. IMSA vs ClonAlign - BAliBASE 2.0 52

53. IMSA vs COBALT, PROBCONS, PCMA, MUSCLE, CLUSTALW - BAliBASE 3.0 53

54. IMSA - BAliBASE 3.0 - SP 54

55. IMSA - BAliBASE 3.0 - CS 55

56. Running time - BAliBASE 3.0 56

57. Outline Introduction & background IMSA Cloning and hypermutation operators Results Conclusion

58. Final Remarks Clonal Selection Algorithm IMSA CLUSTALW-seeding Two specific ad-hoc mutation operators Generating more than a single suboptimal alignment, for every MSA instance. 58

59. Final Remarks, cont. BAliBASE 1.0 IMSA is superior to PRRP, CLUSTALX, SAGA, DIALIGN, PIMA, MULTIALIGN and PILEUP 8. 59

60. Final Remarks, cont. BAliBASE 2.0 high SP, low CS future work - improvement of the CS score 60

61. Final Remarks, cont. BAliBASE 2.0 IMSA shows best performance, and hence best alignments, than both ClonAlign and AIS. 61

62. Final Remarks, cont. BAliBASE 3.0 - new testbed compare with state-of-the-art alignment algorithms, IMSA also shows good alignments. 62

63. Reference http://bips.u- strasbg.fr/fr/Products/Databases/BAliBA SE2/ http://bips.u- strasbg.fr/fr/Products/Databases/BAliBA SE2/ 63

64. Thank you. D00922025 黃任鋒 R00922102 張庭耀 R00922156 陳子筠 R99922158 蘇宏麒 64