MBB 452a (752a12) Syllabus

MB&B 452a / 752a12, Fall 2001

GENOMICS & BIOINFORMATICS

bioinfo.mbb.yale.edu/mbb452a

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

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: Tuesdays 6 pm & Wednesdays 7:30 pm

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

Jeff Sabina Bass 235
e-mail sabina@trna.chem.yale.edu
Dov Greenbaum Bass 437
e-mail dov.greenbaum@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

Discussion of Topics for Final Project

Genomics Section
Sep	05	DS	Genomics: Overview. The Diversity of Life (Life at 110°C, at pH 1, or in %M KCl)
	10	DS	Genomics: Overview of Proteins and Nucleic Acids
	12	DS	Physical and Genetic Maps, Whole Genome Sequences, Annotation
	18, 19	JS	Discussion Sections Week of Sept 17 Doolittle WF. Uprooting the tree of life Sci Am. 2000 Feb;282(2):90-5. (not available on-line) Asai T et al An E. coli strain with all chromosomal rRNA operons inactivated ... Doolittle WF. Phylogenetic classification and the universal tree
	17	DS	Functional Genomics I (array technologies and uses)
	19	MS	Functional Genomics II (gene disruptions, fusions, ect.)
	25,26	JS & DG	Discussion Sections Week of Sept 24 DNA polymorphisms amplified by arbitrary primers are useful as genetic markers Williams JG, Kubelik AR, Livak KJ, Rafalski JA, Tingey SV Nucleic Acids Res. 1990 Nov 25;18(22):6531-5 Happy mapping: a proposal for linkage mapping the human genome Dear PH, Cook PR Nucleic Acids Res. 1989 Sep 12;17(17):6795-807 A high-resolution metric HAPPY map of human chromosome 14 Dear PH, Bankier AT, Piper MB Genomics. 1998 Mar 1;48(2):232-41
	24	MS	Functional Genomics III
	26	MS	Proteomics
Oct	2,3	JS	Discussion Sections Week of Oct 1 Leptin-specific patterns of gene expression in white adipose tissue. Soukas 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.
	01	DS	Structural Genomics
	03	DS	Whole Genome Comparisons
Bioinformatics Section (also includes updated READING LIST) Good Review to Read: What is Bioinformatics
	08	MG	Bioinformatics: Overview
	10	DS	Agricultural Genomics (Robert Last, Cereon )
	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 Proteomics based on selecting and quantifying cysteine containing peptides by covalent chromatography Wang S, Regnier FE J Chromatogr A. 2001 Jul 27;924(1-2):345-57.
	15	MG	Sequence Alignment I (Via Dynamic Programming)
	17	MG	Sequence Alignment II
	16, 17	JS & DG	Discussion Sections Week of Oct 15 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. A comprehensive two-hybrid analysis to explore the yeast protein interactome Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74.
	22	MG	Sequence Alignment III
	23	JS & DG	tentative EXAM REVIEW
	24		MID-TERM EXAM (Covering only the Genomics Section)
	29	MG	Sequence Alignment IV
	31	MG	Databases
	30, 31	DG	Discussion Sections Week of Oct 29 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
Nov	05	MG	Structures
	7	MG	Surveys Quiz Covering up to and including Oct 31 -- databases
	6, 7	JS & DG	Discussion Sections Week of Nov 5 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. 1971 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
	12		Genomics and Society (Claire Fraser)
	14		SNPs & Drug Development (Peter Rae, Bayer Corporation)
	13, 14	JS & DG	Discussion Sections Week of Nov 12 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
	26	MG	Datamining
	28	MG	Simulation Submission of Paper topic DUE by end of the week PLEASE email in a brief note stating your project.
	27, 28	JS & DG	Discussion Sections Week of Nov 27 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, 10:574–584 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
Dec	03	MG	Quiz Covering up to and including Nov 28, Structure and Simulation II Tentative Web Review
	05	MG	Summary (Industrial Perspectives) and Discussion of Final Paper
	4, 5	JS & DG	Discussion Sections Week of Dec 3 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
	13		PAPER DUE BY 9 AM at Joann Delvecchio's Office (Gibbs 309C)

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: Jeff Sabina and Dov Greenbaum
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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