Sequence comparison Dynamic programming by ert554898

VIEWS: 5 PAGES: 21

									 Sequence comparison:
    Local alignment
Genome 559: Introduction to Statistical
   and Computational Genomics
    Prof. William Stafford Noble
           One-minute responses
• It would be helpful to somehow get the solutions for the sample
  problems in our lecture printouts.
    – You can see the solutions by visiting the class web page and opening
      the slides there.
• I am still a little confused about the difference between strings and
  lists.
    – A string is like a tuple of characters. Unlike a string a list is (1) mutable
      and (2) may contain other objects besides characters.
• The Biotechniques paper went into a lot of detail -- how much of this
  should we understand?
    – I intend the paper to provide background for those who are interested.
      You should be sure you understand just what I go over in lecture.
• I am slightly worried because I never seem to do things in the most
  straightforward way.
    – This just takes practice. Often, there is no single best way.
             One-minute responses
•   There was perhaps a bit too much         •   I had somewhat more difficulty
    programming in this class.                   with today's exercises. I think it
•   There was more class time for                was due to the inherent
    Python, which was nice.                      complexity of adding new types to
•   I really liked the sample problem            the repertoire.
    times.                                   •   Class moved at a good speed
•   Problem set is very reasonable.              today.
•   The examples and practice are            •   I enjoyed the pace today.
    most useful teaching methods for         •   Today's pace was good.
    me at least. I am getting                •   The pace was good -- it was
    comfortable with the code through            helpful for me to have more time
    practice.                                    for problems.
•   I like the sample problems. In the       •   Good pace.
    last few classes I felt rushed to        •   Programming problems were a
    finish them, but this time I was             good speed today.
    able to do all 3. It's very satisfying   •   The biostats portion was a little
    when they work.                              fast but manageable.
        One-minute responses
• The cheat sheet really • Reviewing the DP
  helped.                      matrix was very
• I really liked the list of   helpful.
  operations and             • I'm glad we reviewed
  methods on the back          the Needleman-
  of the lecture notes.        Wunsch algorithm.
• Lists of commands in • The traceback review
  slides were helpful.         helped me realize I'd
                               forgotten how to do it.
            Local alignment




• A single-domain protein may be homologous to
  a region within a multi-domain protein.
• Usually, an alignment that spans the complete
  length of both sequences is not required.
BLAST allows local alignments




   Global
 alignment
                       Local
                    alignment
         Global alignment DP
• Align sequence x and y.
• F is the DP matrix; s is the substitution
  matrix; d is the linear gap penalty.
  F 0,0  0
                 F i  1, j  1  sxi , y j 
                 
  F i, j   maxF i  1, j   d
                 F i, j  1  d
                 
          Local alignment DP
• Align sequence x and y.
• F is the DP matrix; s is the substitution
  matrix; d is the linear gap penalty.
  F 0,0   0
                 
                  F i  1, j  1  s xi , y j 
                 
  F i, j   max F i  1, j   d
                  F i, j  1  d
                 
                 0
Local DP in equation form

                       0
F i  1, j  1                   F i, j  1

                   s xi , y j        d

F i  1, j           d             F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2


                                                           A
                         0
                                        F i, j  1
                                                           G
F i  1, j  1

                       s xi , y j           d            C

F i  1, j               d                F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2
                                                                    0        0         0        0
                                                           A        0
                         0
                                        F i, j  1
                                                           G        0
F i  1, j  1

                       s xi , y j           d            C        0

F i  1, j               d                F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A           A      G
  T      -7        -5        -7        2
                                                                    0        0           0      0
                                       0
                                                           A        0          2
                                                                               -5
                                                                                    -5
                                                                                     0

                         0
                                        F i, j  1
                                                           G        0
F i  1, j  1

                       s xi , y j           d            C        0

F i  1, j               d                F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2
                                                                    0        0         0        0
                                                           A        0        2
                         0
                                        F i, j  1
                                                           G        0        ?
F i  1, j  1

                       s xi , y j           d            C        0        ?

F i  1, j               d                F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2
                                                                    0        0         0        0
                                                           A        0        2         ?        ?
                         0
                                        F i, j  1
                                                           G        0        0         ?        ?
F i  1, j  1

                       s xi , y j           d            C        0        0         ?        ?

F i  1, j               d                F i, j 
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2
                                                                    0        0         0        0
                                                           A        0        2         2        0
                         0
                                        F i, j  1
                                                           G        0        0         0        4
F i  1, j  1

                       s xi , y j           d            C        0        0         0        0

F i  1, j               d                F i, j 
            Local alignment
• Two differences with respect to global
  alignment:
  – No score is negative.
  – Traceback begins at the highest score in the
    matrix and continues until you reach 0.
• Global alignment algorithm: Needleman-
  Wunsch.
• Local alignment algorithm: Smith-
  Waterman.
                                       A simple example
                                                        Find the optimal local alignment of AAG and AGC.
         A         C         G         T                Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                    A         A        G
  T      -7        -5        -7        2
                                                                    0        0         0        0
                                                           A        0        2         2        0
                         0
                                        F i, j  1
                                                           G        0        0         0        4
F i  1, j  1

                       s xi , y j           d            C        0        0         0        0
                                                                                   AG
F i  1, j               d                F i, j 
                                                                                   AG
                                            Local alignment
                                                   Find the optimal local alignment of AAG and GAAGGC.
         A         C         G         T           Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                   A        A        G
  T      -7        -5        -7        2                           0        0        0        0
                                                         G         0
                                                         A         0
                         0
F i  1, j  1                        F i, j  1     A         0
                       s xi , y j           d          G         0
                                                         G         0
F i  1, j               d                F i, j 
                                                         C         0
                                            Local alignment
                                                   Find the optimal local alignment of AAG and GAAGGC.
         A         C         G         T           Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                   A        A        G
  T      -7        -5        -7        2                           0        0        0        0
                                                         G         0        0        0        2
                                                         A         0        2        2        0
                         0
F i  1, j  1                        F i, j  1     A         0        2        4        0
                       s xi , y j           d          G         0        0        0        6
                                                         G         0        0        0        2
F i  1, j               d                F i, j 
                                                         C         0        0        0        0
                                            Local alignment
                                                   Find the optimal local alignment of AAG and GAAGGC.
         A         C         G         T           Use a gap penalty of d=-5.
  A      2         -7        -5        -7
  C      -7        2         -7        -5
  G      -5        -7        2         -7                                   A        A        G
  T      -7        -5        -7        2                           0        0        0        0
                                            AAG          G         0        0        0        2

                         0
                                            AAG          A         0        2        2        0
F i  1, j  1                        F i, j  1     A         0        2        4        0
                       s xi , y j           d          G         0        0        0        6
                                                         G         0        0        0        2
F i  1, j               d                F i, j 
                                                         C         0        0        0        0
                 Summary
• Local alignment finds the best match
  between subsequences.
• Smith-Waterman local alignment
  algorithm:
  – No score is negative.
  – Trace back from the largest score in the
    matrix.

								
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