HST.508 | Fall 2002 | Graduate, Undergraduate

Genomics and Computational Biology


LEC # Topics Readings
1 Intro 1: Course overview and introduction to the computational side of computational biology. Why use Perl & Mathematica? Write and run simple scripts. We will also assign sections addressing Biology, computing, and advanced topics. Questionaires due. Mount Chapter 1. Gibas & Jambeck (G&J) Chapters 1, 2, 12 (Those running Unix may find G&J Chaps. 3-5 useful). Students familiar with the above topics should look ahead to next week’s readings.
2 Intro 2: Biological Side of Computational Biology; Central Dogma; Comparative Genomics; Models & Real World Applications
Note: Please take your initial observations about Problem Set#1 to you first section meetings (i.e. check that you actually have access to Perl & Mathematica).
For non-biologists: Primer on molecular biology (PDF) and Molecular Biology for Computer Scientists.
3 DNA 1: Genome Sequencing, Polymorphisms, Populations, Statistics, Pharmacogenomics; Databases.
Note: Problem Set #1 is due at the start of class. (Answers will be posted 48 hrs later.)
Mount Chap. 2 & 7. G&J Chap. 6, 11, pp. 294-303.
Advanced: Pritchard, JK. Are Rare Variants Responsible for Susceptibility to Complex Diseases? Am. J. Hum Gen. 69:124.
4 DNA 2: Dynamic Programming, Blast, Multi-alignment, HiddenMarkovModels. Mount Chap. 3. Durbin Chap. 3-5, G&J Chap. 7, 8 (pp. 191-9). Smith T. F., Waterman M. S. “Identification of Common Molecular Subsequences. J Mol Biol 1981 147:195-7.
5 RNA 1: Microarrays, Library Sequencing and Quantitation Concepts.
Note: Problem Set #2 is due.
Lockhart and Winzeler. Genomics, Gene Expression and DNA Arrays. Mount Chap. 10. G&J pp. 311-317. Nature 2000 405:827-36.
6 RNA 2: Clustering by Gene or Condition and Other Regulon Data Sources Nucleic Acid Motifs; The Nature of Biological “proofs”. Tavazoie et al. Systematic Determination of Genetic Network Architecture. G&J 1999, pp. 205-214. Nature Genetics 22:281-5.
7 Proteins 1: 3D Structural Genomics, Homology, Catalytic and Regulatory Dynamics, Function & Drug Design.
Note: Problem Set #3 is due.
G&J Chap. 9 pp. 215-29 and Chap. 10. Advanced: Thompson J., et al. “Analysis of Mutations at Residues A2451 and G2447 of 23S rRNA in the Peptidyltransferase Active Site of the 50S Ribosomal Subunit.” PNAS 98, 16 (Jul 31 2001): 9002-9007.
8 Proteins 2: Mass Spectrometry, Post-synthetic Modifications, Quantitation of Proteins, Metabolites, & Interactions. Ideker, et al. Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network. Chap. 11 pp. 321-328. G&J. Science 292:929 (2001).
9 Networks 1: Systems Biology, Metabolic Kinetic & Flux Balance Optimization Methods.
Note: Problem Set #4 is due. (#5 will be available but not due until after lecture 13.)
Edwards and Palsson. Metabolic Flux Balance Analysis and the in Silico Analysis of Escherichia Coli K-12 Gene Deletions. BMC Bioinformatics 1, 1 (2000): 1.
Jamshidi, N., et al. Dynamic Simulation of the Human Red Blood Cell Metabolic Network. Bioinformatics 2001 Mar;17(3):286-287.
10 Networks 2: Molecular Computing, Self-assembly, Genetic Algorithms, Neural Networks. Hopfield, J. J. Odor Space and Olfactory Processing: Collective Algorithms and Neural Implementation. PNAS 96, 22 (1999): 12506-12511.
11 Networks 3: The Future of Computational Biology: Cellular, Developmental, Social, Ecological & Commercial Models. Bagowski, C. P., and J. E. Ferrell. Bistability in the JNK Cascade. Curr Biol 2001 Aug 7;11(15):1176-1182.
12 Project Presentations; All written project reports and overhead slides (for presentations) due.  
13 Project Presentations.  
14 Project Presentations; Problem Set #5 due.  

Please note: These “recommended texts” etc. are not required. They are rough order of decreasing relevance. They do not perfectly cover key topics of interest including quantitative functional-genomics, linkage/population genomics, and biosystem modeling. Beginning after the first problem set we will assign readings from primary bioinformatics articles. These will focus on those subjects and help teach the important skills of reading cutting-edge research, but will cover only part of the lecture material.

Tisdall, James. Beginning Perl for Bioinformatics. O’Reilly & Assoc. 2001.

Mount, David. Bioinformatics: Sequence and Genome Analysis. CSHL 2001.

Hunter, L. (ed.) Molecular Biology for Computer Scientists. Recommended for all non-biologists.

Brown, T. A. Genomes. A good biology reference.

Durbin, Richard, S. Eddy, A. Krogh, and G. Mitchison. Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. This book covers basic and advanced models for sequence analysis.

Weiss, Neil A. Introductory Statistics. 5th ed. Addison-Wesley, 1999.

Mathematica 4.2.

Gibas, Cynthia, and Per Jambeck. Developing Bioinformatics Computer Skills. O’Reilly, 2001.

Walsh, Linda. The Perl CD Bookshelf. O’Reilly. This CD contains 6 “books” that might supplement numerous free resources on the web: General Perl documents & download.

Course Info

As Taught In
Fall 2002