MBB 452a (752a12) Syllabus

MB&B 452a / 752a12, Fall 2002

GENOMICS & BIOINFORMATICS

bioinfo.mbb.yale.edu/mbb452a

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

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:6:00PM-6:50PM Tue@BASS405 Wed@WLH113

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

Jason Ptacek, KBT918, 203 432-3510
e-mail jason.ptacek@yale.edu
Haiyuan Yu, Bass 437, 203 432-5405
e-mail haiyuan.yu@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	04	DS	Genomics: Overview. The Diversity of Life (Life at 110°C, at pH 1, or in 5M KCl)
	09	MG	Bioinfomatics: Overview
	10, 11	PY	Discussion Sections Week of Sept 09 Asai T et al An E. coli strain with all chromosomal rRNA operons inactivated ... Doolittle WF. Phylogenetic classification and the universal tree
	11	DS	Genomics: Overview of Proteins and Nucleic Acids
	16	DS	Genomics and Society (Claire Fraser, The Institute for Genome Research)
	18	DS	Genome Sequencing, Sequences Annotation
	17, 18	PY	Discussion Sections Week of Sept 16 Micheal J. Stanhope et al Phylogenetic analyses do not support horizontal gene ransfers from bacteria to vertebrates Steven L. Salzberg et al Microbial Genes in the Human Genome ... International human Genome Sequencing ConsortiumInitial sequencing and analysis of the human genome
	23	DS	Functional Genomics I (array technologies and uses)
	25	DS	Functional Genomics II (proteomics)
	24, 25	PY	Discussion Sections Week of Sep 23 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.
	30	MS	Functional Genomics III
Oct	01	DS	Structural Genomics
	31, 01	PY	Discussion Sections Week of Sep 30 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.
	07	MS	Functional Genomics IV
	09	MS	Functional Genomics V
	9,10	JS	Discussion Sections Week of Oct 8 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.
	14	DS	Genomic Tools in Plant Breeding (Antoni Rafalski, DuPont)
	16	MG	Analysis of Sequences I(Dynamic Programming)
	16, 17	JP	Discussion Sections Week of Oct 14 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.
	21		MID-TERM EXAM (Covering lectures through October 14)
	23	MG	Analysis of Sequences II (Substitution Matrix)
	29, 30	YU	Discussion Sections Week of Oct 28 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
	28	MG	Analysis of Sequences III (HMM)
	30	MG	Analysis of Sequences IV (P-value and EVD)
	5, 6	YU	Discussion Sections Week of Nov 4 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
Nov	04	MG	Analysis of Sequences V (Secondary Structure)
	06	MG	Analysis of Sequences VI (Secondary Structure)
	12, 13	YU	Discussion Sections Week of Nov 11 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
	11	MG	Structure *Quiz 1*: covering up to and including Nov. 04
	13	MG	Database
	19, 20	YU	Discussion Sections Week of Nov 18 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
	18	MG	Survey
	20	MG	Datamining
	3, 4	YU	Discussion Sections Week of Dec 2 Integrative database analysis in structural genomics M Gerstein Nature Structural Biology 2000 7: 960-963. Simulating Water and the Molecules of Life M Gerstein & M Levitt Scientific American 1998 279: 100-105
Dec	02	MG	Simulation
	04	MG	Simulation II *Quiz 2*: covering up to and including Dec 02.

Work Required and Grading

Examination: One midterm exam (covering lectures from September 05 - October 15)
Project: a take-home final exam/project (covering lectures from October 23 - December 5)
Quizzes: Two very short quizes during bioinformatics section (covering lectures from October 23 - December 5)
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: Jason Ptacek and Haiyuan Yu
Grades 40% Genomics Midterm + 32% Bioinformatics Project + 2 * 4% Bioinformatics Quizzes + 20% Discussion Section

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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