Computational Molecular Biology and Genomics Syllabus - Fall 2005


CLASS
DATE
TOPICS
ASSIGNED READING
ADDITIONAL TOPICS
1.  Aug. 30
  • Introduction to computational biology and genomics I

       
    		•   Review biology and algorithms background  
    2.  Sept. 1
  • Introduction to computational biology and genomics I I

       
    		•        
    3.  Sept. 6  Global pairwise sequence alignment
    Lecture outline
    Alignment examples
  • Global sequence alignment notes,
      courtesy Dr. M. Singh, Princeton University
  • Setubal and Meidanis, 47-55, 89-92, 96-98; (electronic reserve)
  • Durbin, pp. 17-22 (electronic reserves)
    		•
  • Saving space: Setubal and Meidanis, 58-60; (physical reserve)
  • General gap penalty functions: Setubal and Meidanis, 60-64 (physical reserve)
    • 4.  Sept. 8  PS0 due.
    Guest lecturer: Rose Hoberman
    Local pairwise sequence alignment.   Semiglobal alignment.
    Alignment examples Lecture outline
  • Local sequence alignment notes,
      courtesy Dr. M. Singh, Princeton University
  • Setubal and Meidanis, 55-57, 64-66; (electronic reserve)
  • Durbin, pp. 23-24, 29-30 (electronic reserves)
    		•   
    5.   Sept. 13   Pairwise alignment summary
    Global Multiple Sequence Alignment
  • Setubal and Meidanis, 69-72 (electronic reserve)
  • Multiple seq. alignment notes I
  • Durbin, 6.1 -- 6.4(electronic reserves)
    		•
  • On the Design of Optimization Criteria for MSA, Durand and Farach-Colton, In Biological Evolution and Statistical Physics, M. Laessig and A. Valleriani
    • 6.   Sept. 15 Global MSA summary, Intro to phylogeny reconstruction
  • Multiple sequence alignment notes, II,
      courtesy Dr. M. Singh, Princeton University
    		•
  • Strategies for multiple sequence alignment, Nicholas HB Jr, Ropelewski AJ, Deerfield DW 2nd, Biotechniques 2002 Mar;32(3):572-4 (electronic reserve)
    • 7.  Sept. 20
  • Introduction to sequencing,  [Slides]  D. Durand
  • Genome Assemblies and Interval Graphs  [Slides]  M. Farach-Colton, Rutgers Univ.

    These presentations will be screened in class.    You can also view these lectures online in Quicktime format.

    		•  

    		 

    8.   Sept. 22   Phylogeny reconstruction, continued.
    Maximum Parsimony
    Durbin, et al: (electronic reserves)
    7.1, 7.2:  Background on trees
    7.4:  Parsimony
    Distance-based methods:
    Durbin, et al: 7.3(electronic reserves)
    Phylogeny notes,
      Dr. M. Singh, Princeton University
    		 Parsimony, nice examples
  • Mount, pp 248-254(physical reserve)

    		•
    9.   Sept. 27   Phylogeny reconstruction cont'd
     Distance-based methods.
    Introduction to class projects

    PS1 due.     		  Distance-based methods
  • Durbin, et al: 7.3(electronic reserves)
  • Phylogeny notes,
      courtesy Dr. M. Singh, Princeton University
    		•   
    10. Sept. 29   Phylogeny reconstruction cont'd
     Distance-based methods.
    Lecture outline
     UPGMA algorithm
     NJ algorithm

    PS2 due.

    		    
    11. Oct. 4   Probabilistic models of evolution (Jukes-Cantor);  Correcting for multiple substitutions.
    Lecture outline
    Markov Chain background
    Ewens and Grant, 4.4-4.8
    Durbin et al., 3.1 (electronic reserves)
    Probabilistic models of evolution
    Durbin, et al: 8.1, 8.2 (electronic reserves)
    Phylogeny notes,  courtesy Dr. M. Singh, Princeton University
    		 
    12. Oct. 6   Jukes-Cantor model continued. Lecture outline
    Durbin, et al: (electronic reserves)
    8.3, 8.4:  Maximum Likelihood
    		 Complexity results:
  • On the Approximability of Numerical Taxonomy: (Fitting Distances by Tree Metrics), Agarwala et al. , (SODA '96) (electronic reserve)
  • Efficient Algorithms for Inverting Evolution, Farach and Kannan, (STOC '96)
    • 13. Oct. 11 Phylogeny Reconstruction
     Maximum Likelihood;  
    Lecture outline

    PS3 due     		   
    14. Oct. 13 Comparison of tree reconstruction methods,   Local Multiple Sequence Alignment.
    Lecture notes
    A PSSM for the WEIRD motif
    A PSSM with pseudocounts

    Project topic statement due
  • Motifs and Profile Analysis,
      courtesy Dr. M. Singh, Princeton University
  • Durbin, et al: p. 102 (electronic reserves)
    		•   Pseudocounts:
  • Durbin, et al: 5.6(electronic reserves)
    • 15. Oct. 18 Midterm Exam
    This exam is closed book. You may bring two pages (or one page, front and back) of your own notes.     		   
    16. Oct. 20 Local MSA continued. Gibbs Sampler.
    Gibb's Sampler lecture notes
    Gibbs sampler
    Ewens and Grant, pp. 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.

    Other motif discovery methods
    17. Oct. 25 Hidden Markov Models I
    Lecture notes
    Citing the literature
    Introduction to Markov models
    Durbin, pp 46-55.
    Ewens and Grant, pp. 327-329 Electronic reserves.
    Viterbi, Forward, Backward algorithms
    Durbin, pp 55 - 61.
    Ewens and Grant, pp. 329-332 Electronic reserves.
    		Hidden Markov Models in Computational Biology: Applications to Protein Modeling,
    Krogh et al., JMB 235, pp 1501--1531,(1994).
    Available through electronic reserves.
    18. Oct. 27 Hidden Markov Models II
      Lecture notes
    Viterbi algorithm example
    Project proposal due     		 

    		 
    19. Nov. 1 Hidden Markov Models III
      Lecture notes
    Forward algorithm example

    		 
    20. Nov. 3 Hidden Markov Models IV
      Lecture notes
    Profile HMMs
    Durbin, pp 100 - 113.
    Ewens andGrant, pp. 335-337 Electronic reserves.
    HMM topology: Durbin, pp 61-71 Electronic reserves.
    Parameter estimation, Baum-Welsh algorithm
    Durbin, pp 61-71
    Ewens and Grant, pp. 329-332 Electronic reserves.
    Multiple alignment using HMMs
    Ewens and Grant, pp. 337 - 339 Electronic reserves.
    		 
    21. Nov. 8 Substitution Matrices
      PAM matrices

     Lecture notes
    Substitution matrices:
    Setubal and Meidanis, 80-84; (electronic reserve)
    Mount, pp 76-89; (electronic reserve)
    Durbin et al, pp 14-16 (electronic reserves)
    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 (electronic reserve)
    		  
    22. Nov. 10 Substitution matrices cont'd
     Lecture notes
    		    
    23. Nov. 15 Database searching; BLAST
    Lecture notes

      BLAST home page

      BLAST Tutorial page  Recommended for students unfamiliar with BLAST
    Data Base Searching
    Mount, pp. 282-291 (electronic reserve)

    BLAST
    Setubal and Meidanis, 84-87 (electronic reserve)
    Basic local alignment search tool, Altschul et al. , J. Mol. Bio., 1990 (electronic reserve)
    		 
    24. Nov. 17 PS 4 due in class

    BLAST; statistics of local, ungapped alignments.
      Lecture notes     		The statistics of sequence similarity scores S. F. Altschul  

    Strategies for searching sequence databases, Nicholas HB Jr, Ropelewski AJ, Deerfield DW 2nd, Biotechniques 2002 Jun;28(6):1174-8 (electronic reserve)
    Blast statistics:
    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)
    Statistical Methods in Bioinformatics, W. Ewens and G. Grant (Physical reserves)

    Other BLAST references
    25. Nov. 22 Gapped BLAST, Lecture notes


    PAM 30,   PAM 250     		Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Altschul et al., Nucleic Acids Research, 1997, pp. 3389 - 3394 (electronic reserve)

    		 
      Nov. 24  No class (Thanksgiving Holiday)    
    26. Nov. 29 Prokaryotic Gene Finding,   Lecture notes
    FCE's  
  • Defining genes in the genomics era.
    Snyder and Gerstein, Science (2003) 300(5617):258-60.
  • Gene Discovery in DNA Sequences
    S. Salzberg, IEEE 1999 (electronic reserve)
  • A hidden Markov model that finds genes in E. coli DNA A. Krogh et al., NAR 1994 (electronic reserve)
    		•
  • Assessment of protein coding measures
    J.W. Fickett and C.S. Tung, NAR 1992 (electronic reserve)
  • Distinctive sequence features in protein coding genic non-coding, and intergenic human DNA R. Guigo and J.W. Fickett, JMB 1995 (electronic reserve)
    • 27. Dec. 1 Eukaryotic Gene Finding Lecture notes

    		 Yeast rises again.
    S. Salzberg, Nature ( 2003) 423, 233-234
  • Prediction of Complete Gene Structures in Human Genomic DNA C. Burge and S. Karlin, JMB 1997 (electronic reserve)
  • Ewens and Grant, pp. 340-346.

  • Evaluation of Gene Structure Prediction Programs M. Burset and R. Guigo, Genomics 1996 (electronic reserve)
    • 28. Dec. 6 Project presentations

       PS5 due in class.
    		    
    29. Dec. 8 Project presentations

       Project final papers due.     		       
      Dec. 19 Final Exam:
      1pm - 4pm; Room HH B131
    This exam is closed book. You may use two 8.5x11 pages of your own notes. Bring a calculator.

    Study questions

    		   
    To view online lectures in Quicktime format, you will need to have within your browser the QuickTime plug-in, and select it as the player for all media files. You can download the QuickTime Movie player for a PC or Mac free of charge at: http://www.apple.com/quicktime/download/index.html.



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    Last modified: November 28th, 2005.
    Maintained by Dannie Durand (durand@cs.cmu.edu).