MBB 452a (752a12) Syllabus

MB&B 452a / 752a12, Fall 2003

GENOMICS & BIOINFORMATICS

bioinfo.mbb.yale.edu/mbb452a

Previous Year's Course Pages (all links still work)

Fall 2002, Fall 2001, Fall 2000, Fall 1999, Spring 1999, Spring 1998

Timing and Location

Meeting from 1:00-2:15 PM on Mondays and Wednesday, in Bass 305.

Discussion Section Times:6:30PM-7:30PM Mondays @ BASS405

The papers for the discussion are only available from a Yale University Domain

Instructors

Genomics Section

Dieter Söll
Bass 238, Phone 203 432-6200, e-mail dieter.soll@yale.edu
Handouts and readings with Ava Artaiz <ava.artaiz@yale.edu> Bass 238, 203 432-6203.

Michael Snyder
KBT 926, Phone 203 432-6139, e-mail michael.snyder@yale.edu

Bioinformatics Section

Mark Gerstein
Bass 432A, Phone 203 432-6105, e-mail Mark.Gerstein@yale.edu
Handouts and readings with Joann Delvecchio <joann.delvecchio@yale.edu> J W Gibbs 309C, 203 432-5566.

Teaching Fellows

John Rinn, KBT944, 203 432-5730
e-mail john.rinn@yale.edu
Michael Seringhaus, Bass 437, 203 432-5405
e-mail michael.seringhaus@yale.edu

Brief Description

Genomics describes the determination of the nucleotide sequence as well as many further analyses used to discover functional and structural gene information on all the genes of an organism. Topics include the methods and results of analysis on a genome-wide scale as well as a discussion of the implications of this research. Bioinformatics describes the computational analysis of gene sequences and protein structures on a large scale. Topics include sequence alignment, biological database design, geometric analysis of protein structure, and macromolecular simulation. [Blue Book Entry]

Rough Outline of Topics

Genomics Section
Sep	03	DS	Genomics: Overview. The Diversity of Life (Life at 110°C, at pH 1, or in 5M KCl)
	08	DS	Genomics: Overview of Proteins and Nucleic Acids
	08	JLR/MRS	Discussion Sections Week of Sept 08 Asai T et al An E. coli strain with all chromosomal rRNA operons inactivated ... Doolittle WF. Phylogenetic classification and the universal tree
	10	DS	Genome Sequencing, Sequence Annotation and Bioinformatics tools for Genomics
	15	DS	Functional Genomics I (array technologies and uses)
	15	JLR/MRS	Discussion Sections Week of Sept 15 Jason W. Chin et al An expanded eukaryotic genetic code
	17	DS	Functional Genomics II (proteomics)
	22	DS	Structural Genomics
	22	JLR/MRS	Discussion Sections Week of Sep 22 Leptin-specific patterns of gene expression in white adipose tissue. S oukas A, Cohen P, Socci ND, Friedman JM. Genes Dev. 2000 Apr 15;14(8):963-80. DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide. Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G. J Bacteriol. 2001 Aug;183(15):4562-70.
	24	MS	Functional Genomics III
	29	MS	Functional Genomics IV
	29	JLR/MRS	Discussion Sections Week of Sep 29 Biomedical Discovery with DNA arrays Young, R. Cell. 2000 July 7;102:9-15. Gene expression profiling predicts clinical outcome of breast cancer. Veer et al. Nature. 2002 Jan 31;415:530-535.
Oct	01	MS	Functional Genomics V
	06	JLR/MRS	Yom Kippur (Genomics Assignment)
	6?	JLR/MRS	Discussion Sections Week of Oct 6 Integrated genomic and proteomic analyses of a systematically perturbed metabolic network Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L. Science. 2001 May 4;292(5518):929-34 *Functional Characterization of the S. cerevisiae* genome ...** Winzeler et al Science. 1999 Aug 6;285:901-906.
	08	KC	Web Resources for Genomics I (Kei-Hoi Cheung)
	13	JLR	Microarrays: How to do it! (John Rinn)
	13	JLR/MRS	Discussion Sections Week of Oct 13 Global analysis of protein activities using proteome chips Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R,Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M. Science. 2001 Sep 14;293(5537):2101-5. Functional organization of the yeast proteome by systematic analysis of protein complexes Gavin et al. Nature. 2002 Jan 10;415:141-147. Genome-wide mutant collections: toolboxes for functional genomics Coelho P, Kumar A, Snyder M. Curr Opin Microbiol. 2000 Jun;3(3):309-15.
	15	DS	Whole Genome Comparisons
	20		Midterm Exam (covering lectures through October 15)
	20	JLR/MRS	Discussion Sections Week of Oct 20 No discussion -- midterm today!
	22	MG	Bioinfomatics: Overview
	27	MG	Analysis of Sequences I
	27	JLR/MRS	Discussion Sections Week of Oct 27 Interrelating Different Types of Whole-genome Data, from Proteome to Secretome: 'Oming in on Function D Greenbaum, N M Luscombe, R Jansen, J Qian, M Gerstein. Genome Res. 2001 Sep;11(9):1463-8 What is bioinformatics? A proposed definition and overview of the field N Luscombe, D Greenbaum, M Gerstein Methods Inf Med. 2001;40(4):346-58
	29	MG	Analysis of Sequences II (Substitution Matrix)
Nov	03	MG	Analysis of Sequences III (HMM)
	5, 6	JLR/MRS	Discussion Sections Week of Nov 3 A general method applicable to the search for similarities in the amino acid sequence of two proteins Needleman, S. B. & Wunsch, C. D. J. Mol. Biol. 1970 48: 443-453. Issues in searching molecular sequence databases. Altschul, S. F., Boguski, M. S., Gish, W. and Wootton, J. C. Nature Genetics. 1994 6(2): 119-29. A Unified Statistical Framework for Sequence Comparison and Structure Comparison. M Levitt & M Gerstein PNAS 1998 95: 5913-5920
	05	MG	Analysis of Sequences IV (P-value and EVD)
	10	MG	Database
	10	JLR/MRS	Discussion Sections Week of Nov 10 Hidden Markov models Eddy, S. R. Curr. Opin. Struc. Biol. 1996 6, 361-365. Protein Structure Comparison by Alignment of Distance Matrices Holm, L. and Sander J. Mol. Biol. 1993 233: 123-128 Identification and application of the concepts important for accurate and reliable protein secondary structure prediction King, R. D. & Sternberg, M. J. E. Prot. Sci. 1996 5, 2298-2310
	12	MG	Structure
	17	DS	Genomics: New Frontiers for Nutrition and Foods (Beat Mollet, Nestle)
	17	JLR/MRS	Discussion Sections Week of Nov 17 The current excitement in bioinformatics, analysis of whole-genome expression data: How does it relate to protein structure and function? M Gerstein & R Jansen Current Opinion in Structural Biology 2000, 10:574~V584 Cluster analysis and display of genome-wide expression patterns Eisen MB, Spellman PT, Brown PO, & Botstein D Proc Natl Acad Sci U S A 1998 95: 14863-8
	19	MG	Surveys I
Dec	01	MG	Datamining
	01	JLR/MRS	Discussion Sections Week of Dec 1 A Bayesian Networks Approach for Predicting Protein-Protein Interactions from Genomic Data R Jansen, H Yu, D Greenbaum, Y Kluger, N Krogan, S Chung, A Emili, M Snyder, J Greenblatt and M Gerstein Science 2003 302: 449-453 Simulating Water and the Molecules of Life M Gerstein & M Levitt Scientific American 1998 279: 100-105
	03	MG	Simulation

Work Required and Grading

Examination: One midterm exam (covering lectures from September 03 - October 15)
Project: a take-home final exam/project (covering lectures from October 22 - December 3)
Quizzes: Two very short quizes during bioinformatics section (covering lectures from October 22 - December 3)
Literature Discussion Section One session of 60 minutes per week. Student Presentations of recent research papers relevant to the topics of the course.
Led by TAs: John Rinn, Michael Seringhaus
Grades 40% Genomics Midterm + 32% Bioinformatics Project + 2 * 4% Bioinformatics Quizzes + 20% Discussion Section (includes Oct 6 genomics assignment)

Prerequisites

The course is keyed towards advanced MB&B undergraduates and graduate students wishing to learn about types of large-scale quantitative analyses that whole-genome sequencing will make possible. It would also be suitable for students from other fields such as computer science or physics wanting to learn about an important new biological application for computation.
Students should have :
1. A basic knowledge of biochemistry and molecular biology.
2. A knowledge of basic quantitative concepts, such as single variable calculus, some probability and statistics, and basic programming skills.
These can be fulfilled by the following prerequisites statement: "Prerequisites: MB&B 200 and Mathematics 115 or permission of the instructor."

Research Jobs in Bioinformatics

If you're really motivated, take a look at http://bioinfo.mbb.yale.edu/jobs.

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