03511 - Syllabus

Computational Molecular Biology and Genomics - Syllabus, Fall 2019

The materials in the "Assigned Reading" column are directly related to the topics covered in class. Readings under "Additional Topics" are strictly optional and will not be covered on the exams.

In some cases, the same material is covered in more than one textbook. You have the choice of selecting the text that presents a treatment of the material most to your liking. It is your responsibility to make sure that you understand the material covered in class and you may read as many or as few of these texts needed to achieve that goal.

Go to Google calendar (does not include links to homework or readings).

1.   Aug. 27
  • Introduction to computational biology and genomics
  • Pairwise sequence alignment, Intro and Box1

  • PS0 due Tuesday, Sept. 3rd in class
    Review biology and algorithms background
    2.  Aug. 29 Global pairwise sequence alignment, pp 2-9
    Alignment example - distance scoring.
    Global pairwise alignment
    - Setubal and Meidanis, 47-57, 89-92, 96-98; (electronic reserve)
    - Durbin, 17-24 (electronic reserves)
    3.  Sep. 3 Global and semiglobal alignment, pp 6-11
    Global Alignment example - similarity scoring.

    Semi-global alignment
    - Setubal and Meidanis, 56-57, (electronic reserve)
  • Saving space, Setubal and Meidanis, 58-60; (physical reserve)
  • General and affine gap penalty functions,
    - Setubal and Meidanis, 60-66 (physical reserve)
    - Durbin, 29-30 (electronic reserves)
  • 4.  Sep. 5 Semiglobal and local pairwise alignment, pp 10-13
    Example - Semi-Global Alignment.
    Example - Local Alignment.

    PS1 due 4pm Friday, Sept. 13th Additional alignment template
    Local pairwise alignment
    - Setubal and Meidanis, p. 55, (electronic reserve)
    - Durbin, 23-24 (electronic reserves)
    5.  Sep. 10 Introduction to Markov chains, pp 15-20

    Seven11 assignment 1 due Wednesday, Sept. 18th by 5pm
    Linear alignment template
    Affine gap alignment template
    Markov Chain background
    - Ewens and Grant, 4.4-4.8 (electronic reserves)
    - Durbin et al., 48-51 (Section 3.1) (electronic reserves)
    6.  Sep. 12 Markov models continued, pp 20-27

    PS1 due tomorrow (Friday) at 4pm
    PS2 due 4pm Friday, Sept. 20th
    7.  Sep. 17 Markov models of DNA evolution, pp 27-32

    Seven11 assignment 1 due tomorrow (Wednesday) at 5pm
    Models of nucleotide substitution
    - Durbin et al., 8.2, pp. 193 - 197 only (electronic reserves)
    8.  Sep. 19 Applications of Markov models of DNA evolution pp 32-38

    PS2 due tomorrow (Friday) at 4pm
    PS3 due 4pm Friday, Sept. 27th
    9.  Sep. 24 More complex applications of Markov models of DNA evolution pp 39-45

    Seven11 assignment 2 due Wednesday, Oct. 2nd by 5pm
    10.  Sep. 26 Log-odds scoring

    PS3 due tomorrow (Friday) at 4pm
    PS4 due 4pm Friday, Oct. 4th
    11.  Oct. 1 Amino acid substitution, PAM matrices, pp 50-57

    Seven11 assignment 2 due tomorrow (Wednesday) at 5pm
    Substitution matrices:
    - Setubal and Meidanis, 80-84; (electronic reserve)
    - Mount, pp. 76-89; (electronic reserve)
    - Durbin et al, pp. 14-16 (electronic reserves)
    12.  Oct. 3 Amino acid subst. matrices cont'd pp 58-60

    PS4 due tomorrow (Friday) at 4pm
    In-class EXAM I TUESDAY.
    Study guide  
    13.  Oct. 8 In-class exam I
    This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.

    Seven11 assignment 3 due Thursday, Oct. 17th by 5pm
    Page & Holmes, pp.187-189.
    Study guide  
    14.  Oct. 10 Comparing the PAM and BLOSUM matrices, pp 61-66
      Excel file of PAM and BLOSUM matrices
      PAM250,   BLOSUM62   PAM30

    PS5 due 4pm Monday, Oct. 21st
    BLOSUM Matrices:
    - Ewens and Grant, 6.5.2. (electronic reserves)
    - Amino acid substitution matrices from protein blocks, Henikoff S, Henikoff JG., PNAS 89(22):10915-9, 1992 (electronic reserve)
    15.  Oct. 15 Modeling Motifs: PSSMs, pp 67-70
    PSSM example, with and without pseudocounts.

    Seven11 assignment 3 due Thursday at 5pm
    Gibbs sampler
    Ewens and Grant, 211-215. (electronic reserve).
    Theoretical framework, convergence proofs
    - Ewens and Grant, 10.5.2, (physical reserves).
    - Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment, Lawrence et al., Science. 1993 262(5131):208-14.
    - Explaining the Gibbs sampler, G. Casella & E. I. George, The American Statistician, 46:167-174, 1992
    16.  Oct. 17 The Gibbs Sampler, pp 70-75
    Handout of the algorithm for Gibbs sampling.

    PS5 due MONDAY at 4pm
    17.  Oct. 22 Hidden Markov Models, pp 77-84
    Handout summarizing HMM algorithms.

    Seven11 assignment 4 due Wednesday, Oct. 30th by 5pm
    What is an HMM?
    - Ewens & Grant, 327-329 (electronic reserves)
    - Durbin et al, 53-55 (electronic reserves)
    18.  Oct. 24 HMMs continued, pp 77-84

    PS6 due 4pm Friday, Nov. 1st
    19.  Oct. 29 Hidden Markov Models: Recognition, pp 84-92

    Seven11 assignment 4 due tomorrow (Wednesday) at 5pm
    Viterbi, Forward, Backward algorithms
    - Durbin et al, 55 - 61 (electronic reserves)
    - Ewens and Grant, 329-332
    (electronic reserve).
    20.  Oct. 31 Hidden Markov Models: Recognition, pp 84-92

    PS6 due tomorrow (Friday) at 4pm
    21.  Nov. 5 HMM design: Parameter estimation, topology, pp 92-100

    In-class EXAM II THURSDAY.
    Study guide
    HMM Topology
    Durbin et al, 68-71 (electronic reserves)
    Parameter estimation, Baum-Welch algorithm
    Durbin et al, 61-71 (electronic reserves)
    Ewens & Grant, 329-332 (electronic reserves)
    22.  Nov. 7 In-class exam II
    This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.
    Study guide  
    23.  Nov. 12 Profile HMMs, Hidden Markov Models for global multiple alignment, pp 100-108

    Seven11 assignment 5 due Wednesday, Nov. 20th by 5pm
    Profile HMMs
    Durbin et al, 100-110 (electronic reserves)
    Multiple alignment using HMMs
    Ewens & Grant, 335 - 337 (electronic reserves)
    24.  Nov. 14 Blast heuristics, pp 115-121

    PS7 due 4pm Friday, Nov. 22nd
    Blast 1990
    - Setubal and Meidanis, 84-87 (electronic reserve)
    - Basic local alignment search tool, Altschul et al. , J. Mol. Bio., 1990 (electronic reserve)
    - Strategies for searching sequence databases, Nicholas HB Jr, Ropelewski AJ, Deerfield DW 2nd, Biotechniques 2002 Jun;28(6):1174-8 (electronic reserve)
    Blast statistics and data base searching
    The statistics of sequence similarity scoresS. F. Altschul
    25.  Nov. 19 Gapped BLAST, pp 115-121

    Seven11 assignment 5 due tomorrow (Wednesday) at 5pm
    26.  Nov. 21 BLAST statistics, pp 121-132

    PS7 due tomorrow (Friday) at 4pm
    PS8 due 4pm Wednesday, Dec. 4th due 6pm Friday, Dec. 6th
    Extra copies of the tables
    Excel version of the tables
    Blast statistics and data base searching:
    - The statistics of sequence similarity scores S. F. Altschul
    - Amino acid substitution matrices from an information theoretic perspective, S. F. Altschul, J. Mol. Bio., 219:555-565, 1991 (electronic reserve).
    - A protein alignment scoring system sensitive at all evolutionary distances, S. F. Altschul, J. Mol. Evol., 36:290-300, 1993 (electronic reserve).
    27.  Nov. 26 Class cancelled. Have a wonderful Thanksgiving holiday!  
      Nov. 28 Thanksgiving Holiday: No class
    28.  Dec. 3 Global multiple sequence alignment, pp 133-138

    Seven11 assignment 6 due Friday, Dec. 6th by 5pm due Monday, Dec. 8th by 6pm
    Altschul 05
    Global multiple alignment using dynamic programming
    - Setubal and Meidanis, 69-72 (electronic reserve)
    - Durbin, 6.1 -- 6.3 (electronic reserve)
    29.  Dec. 5 Progressive multiple alignment, pp 138-142

    PS8 due tomorrow (Friday) at 6pm
    Seven11 assignment 6 due Monday at 6pm
    PS9 due 4pm Wednesday, Dec. 11th
    This homework is optional. If you submit on time, I will drop your two lowest Problem Set grades.
    Global MSA with the progressive alignment heuristic
    Durbin, 6.4 (electronic reserve)
    Protein multiple sequence alignment, Do and Katoh, 2008. (electronic reserves)
    Final exam TBA Final Exam
    This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.

    Study guide
    The exam covers the entire semester, but with a strong emphasis on the last third of the course.
    The time and date of the final exam are determined by the registrar's office and are beyond my control. You must take the final exam at the time scheduled.

    Until the date of the final is determined, you should not make plans to leave for winter vacation before the end of the exam period.

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    Last modified: September 12, 2019.
    Maintained by Maureen Stolzer.