03511/03711 - Syllabus

Computational Molecular Biology and Genomics - Syllabus, Fall 2024


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.

Access to full Lecture Notes Lecture Notes


   
CLASS
DATE
TOPICS
ASSIGNED READING
ADDITIONAL TOPICS
1.   Aug. 27 Introduction
Pairwise sequence alignment (lecture notes, pp. 1 - 13)

Review biology and algorithms background
2.  Aug. 29 Global pairwise sequence alignment
(lecture notes, Section 1.1)

Global alignment examples
similarity scoring.
distance scoring.
Global pairwise alignment
- Setubal and Meidanis, 47-57, 89-92, 96-98;
- Durbin, 17-24


  • 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
  • Semi-global alignment
    - Setubal and Meidanis, 56-57,
  • 3.  Sep. 3 Local pairwise alignment
    (lecture notes, Section 1.2)

          Local alignment examples.


    PS0 DUE 9:30am via Canvas  

    Local pairwise alignment
    - Setubal and Meidanis, p. 55,
    - Durbin, 23-24
    4.  Sep. 5 Introduction to Markov chains.



    Markov Chain background
    - Ewens and Grant, 4.4-4.8
    - Durbin et al., 48-51 (Section 3.1)
    5.  Sep. 10 Markov chains, Lecture Notes Sections 2.1, 2.2



     
    6.  Sep. 12 Markov models of sequence evolution, applications of DNA substitution models (lecture notes, Sections 2.3)
    Today's slides

    Models of nucleotide substitution
    - Durbin et al., 8.2, pp. 193 - 197 only
     
    7.  Sep. 17 Markov models of sequence evolution, applications of DNA substitution models (lecture notes, Sections 2.3, 2.4)
    Today's slides

     
    8.  Sep. 19 Markov models of sequence evolution, applications of DNA substitution models (lecture notes, Section 2.4)

    Log-odds scoring
    (lecture notes, Section 3.1)

     
    9.  Sep. 24 Amino acid substitution matrices: PAM matrices (lecture notes, Section 3.2)

    Today's slides

    Substitution matrices:
    - Setubal and Meidanis, 80-84;
    - Mount, pp. 76-89;
    - Durbin et al, pp. 14-16
     
    10.  Sep. 26 Amino acid substitution matrices: PAM matrices (lecture notes, Section 3.2)     Today's slides

         PAM30,   PAM250

     
    11.  Oct. 1 In-class EXAM 1
      - This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.
      - The exam covers material covered in Lectures 1 through 8.

    Study Guide

     
    12.  Oct. 3 Substitution matrices, continued.
        Today's slides

      BLOSUM62



    BLOSUM Matrices:
    - Ewens and Grant, 6.5.2.
    - Amino acid substitution matrices from protein blocks, Henikoff S, Henikoff JG., PNAS 89(22):10915-9, 1992
    13.  Oct. 8 Motifs, local multiple sequence alignment, PSSMs
    PSSM class notes: Section 4.1
    PSSM examples
    pseudocount: b=1
    pseudocount: b=0.1


    Today's slides

    Gibbs sampler
    Ewens and Grant, 211-215.
    14.  Oct. 10 Motif discovery: The Gibbs Sampler

    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
      Oct. 15 & Oct. 17
    Mid semester break, NO CLASS.
       
    15.  Oct. 22 Review: in-class exam, PSSMs, Gibbs sampler.

    16.  Oct. 24
    Hidden Markov models (HMMs)     Today's slides

         Introduction, Lecture Notes 5.1-5.3


    Tutorial on Hidden Markov Models, L.R. Rabiner, Proc. IEEE, 1989  
    17.  Oct. 29 Designing HMMs: topology and parameter estimation with labeled sequences
        Today's slides

    HMM Design
    - Durbin et al, Durbin et al, HMM model structure: Section 3.4, pp. 68 - 71
    - Lecture notes, Section 5.6, pp. 108-112

     
    18.  Oct. 31 HMMs: Recognition algorithms Today's slides
         
    Viterbi example,
    Forward example.
    Viterbi, Forward, Backward algorithms
    - Durbin et al, 55 - 61
    - Ewens and Grant, 329-332
     
      Nov. 5 Election Day; No class

     
    19.  Nov. 7 Parameter estimation, Baum Welch

     
    20.  Nov. 12 In-class EXAM 2

    Study Guide
      - This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.
      - The exam covers material covered in Lectures 9 through 17.



     
    21.  Nov. 14 Profile HMMs Lecture notes, section 5.7


     
    22.  Nov. 19 Multiple alignment using Profile HMMs. Lecture notes, section 5.7
    Profile HMM alignment example

    Exam statistics

    Profile HMMs
    Durbin et al, 100-110
    Multiple alignment using HMMs
    Ewens & Grant, 335 - 339
    23.  Nov. 21 Searching sequence databases
    The Basic Local Alignment Search Tool (Blast). Lecture notes, section 6.1


    Blast 1990
    - Setubal and Meidanis, 84-87
    - Basic local alignment search tool, Altschul et al. , J. Mol. Bio., 1990
     
    24.  Nov. 26 Blast Statistics
      Today's slides
    Blast statistics and data base searching:
    - The statistics of sequence similarity scores S. F. Altschul
      Nov. 28 Thanksgiving Holiday: No class

     
    25.  Dec. 3
    The statistics of database searching
    • Information content of substitution matrices
    • Information content of alignments


    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.
    - A protein alignment scoring system sensitive at all evolutionary distances, S. F. Altschul, J. Mol. Evol., 36:290-300, 1993.
    26.  Dec. 5
    The statistics of database searching
    • Which substitution matrix will maximize precision and recall?


    Final exam
    Monday, Dec 9th
    1pm-4pm

    Location: TBD
    Final exam
    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: Aug 26, 2024.