BMS 516: Molecular Genetics and Genomics
Course Instructors:  Stephanie Ruby, Susan Atlas,
Scott Ness, and Mary Ann Osley

Teaching Assistant:  Erik Barry Erhardt

Molecular Genetics and Genomics
Spring Semester 2005
Course Call Number 15280
Time TR 2:45pm--4:15pm
Location Dept Room/HSC Lib 226
Website http://www.stat.unm.edu/~erike/courses/bms516/
Syllabus doc

textbook cover image
Textbook Johnathon Pevsner (2003), Bioinformatics and functional genomics. Wiley-Liss Press.
Other course materials on reserve in the HSC library and/or at the class website:
        research articles
        supplementary text "The Cell Cycle by A.W. Murray and T. Hunt, Freeman and Co., 1993
Other suggested materials You may want to bring in a CD or flashdrive for each lab if you wish to back up your work.

Course Director
Stephanie Ruby e-mail, 272-5830, CRTC 330
Instructors
Susan Atlas e-mail web, 277-1509, Physics 1105
Scott Ness e-mail web, 272-9883, CRF 125
Mary Ann Osley e-mail, 272-4839, CRF 123.
Marianne Berwick (Guest lecturer) e-mail, 272- , RIB
Teaching Assistant
Erik Barry Erhardt e-mail web, 272-4813, Humanities 346
Students
Jennifer Buntz e-mail
Leyma Deharo e-mail
Rafael Medina e-mail (audit)
(David Davis e-mail) (drop 3/26/05)

Grading

3 lab projects: 15% each (45%)
3 lab problems: 5% each (15%)
2 exams: 10% each (20%)
2 paper presentations: 10% each (20%)
credit/nocredit for some labs

Catalog Description
Genetic and genomic approaches in model organisms and humans to study biological processes at the molecular, cellular, tissue, organism population and evolutionary levels. It also provided an introduction to bioinformatics and computational methods used in such studies.

Prerequisites
BMS507 and BMS 508, or equivalent courses and consent of the course director Stephanie Ruby e-mail.

Detailed Course Description
Modern biology requires a knowledge of genetics and gene function as well as a familiarity with the bioinformatic methods necessary to tackle difficult problems. This course is an introduction for biologists who need to become familiar with basic computational and computer methods required for pursuing modern genetic and genomic problems. The course will build on a basic understanding of genetics and genomics by focusing on an important but highly relevant topic regulation of the cell cycle in yeast and mammalian cells. It will combine lectures with laboratory exercises and instruction on computer-based methods. Special emphasis will be placed on sequence analysis, transcription profiling, gene and protein regulatory networks, signal transduction and regulation. The goal is for students to develop both an understanding of the cell cycle and the ability to access and manipulate genetic and genomic information using currently available computer programs and web-based tools.
Announcements

1/20/05
Reading:
  1. Chapters 1-4; 6, 8 of "The Cell Cycle, an Introduction"
1/27/05
Reading:
  1. Chapter 6 in the textbook, "Bioinformatics and functional genomics".
  2. Paper_1-27-05_Breeden_2003.pdf
  3. Paper_1-27-05_Cho_1998.pdf
  4. Paper_1-27-05_Simon_2001.pdf
  5. Paper_1-27-05_Spellman_1998.pdf
2/1/05
Reading:
From textbook (Bioinformatics and Functional Genomics):
  1. Chapter 7, Gene Expression: Microarray Data Analysis
Background for in-class/take-home lab (Feb 8):
  1. EisenCluster.pdf - Eisen et al., “Cluster analysis and display of genome-wide expression patterns," PNAS 95:14863-14868 (1998).
  2. Bittner2000.pdf (supplemental) - Bittner et al., "Molecular classification of cutaneous melanoma by gene expression profiling," Nature 406:536-540 (2000).
On mathematics and computation in biology:
  1. Bialek_Botstein04.pdf - Bialek and Botstein, Science 303:788-790 (2004).
2/15/05
Reading assignment (February 15 and 17 lectures; * = required)
  1. Paper_2-15-05_SimonBJC.pdf - R. Simon, Diagnostic and prognostic prediction using gene expression profiles in high-dimensional microarray data.  Br. J. Cancer 89:1599-1604 (2003).  [Review]
  2. *Paper_2-15-05_Simon_JNCI_1999.pdf - R. Simon et al., Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification.  J. National Cancer Inst. 95:14-18 (2003).
  3. Paper_2-15-05_Guyon2002.pdf - I. Guyon et al. Gene selection for cancer classification using support vector machines.  Machine Learning 46:389422 (2002).  [SVM]
  4. *Paper_2-15-05_Khan2001.pdf - J. Khan et al. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nature Medicine 7:673 (2001). [Neural networks]
  5. Paper_2-15-05_Dudoit_TR576.pdf - S. Dudoit et al. Comparison of discrimination methods for the classification of tumors using gene expression data. Technical Report #576, June, 2000, Dept. Statistics, UC Berkeley (Berkeley, CA). [Discriminant analysis]
  6. *Paper_2-15-05_Dudoit_JASA_2002.pdf - S. Dudoit et al. Comparison of discrimination methods for the classification of tumors using gene expression data.  J. Am. Stat. Assoc. 97:77-87 (2002) (short/edited version of above technical report).
  7. Paper_2-15-05_Multiclass_PNAS_2001.pdf - S. Ramaswamy et al. Multiclass cancer diagnosis using tumor gene expression signatures.  Proc. Natl. Acad. Sci. USA 98:15149-15154 (2001).
  8. Paper_2-15-05_Friedman_2000.pdf - A. Ben-Dor et al. Tissue classification with gene expression profiles. J. Comp. Biol. 7(3,4):559-584 (2000).  [Highly technical, but important paper; ROC, TNoM]
  9. Paper_2-15-05_Helman_etal_JCompBiol2004.pdf - P. Helman et al. Bayesian networks for classification of gene expression data.  J. Comp. Biol 2004. [Highly technical, but gives a sense of the application of Bayesian networks to microarray classification problem].
Background References and Further Reading (optional)
Pattern Recognition, general
  1. C. M. Bishop. Neural Networks for Pattern Recognition. (Oxford, New York, 1995).
  2. R. O. Duda, P. E. Hart, and D. G. Stork.  Pattern Classification, Second Edition. (Wiley, New York, 2000).
  3. Paper_2-15-05_Jain_1999.pdf - A. K. Jain, R. P. W. Duin, and J. Mao. Statistical Pattern Recognition: A Review.  Preprint, November, 1999.   (posted on website)
Statistical Analysis and Learning (with varied emphasis on microarray data)
  1. T. Hastie, R. Tibshirani, and J. Friedman.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction.  (Springer, New York, 2001).
  2. T. Speed, ed. Statistical Analysis of Gene Expression Microarray Data.  (Chapman and Hall/CRC, 2003). 
  3. S. Draghici. Data Analysis Tools for DNA Microarrays. (Chapman and Hall/CRC, 2003).

2/17/05
Reading:
  1. Quackenbush.pdf - J. Quackenbush, Computational analysis of microarray data.  Nature Rev. 2: 418-427 (2001)  [Review]
2/22/05
Reading assignment (February 22 lecture and 24  lab; * = required)
  1. *Khan et al. - (previously posted)
  2. *Ramaswamy et al. - (previously posted)
  3. *GAKNN.pdf - L. Li et al, Bioinformatics 17:1131-1142 (2001)
  4. MIT-leukemia.pdf - T. R. Golub et al., Science 286:531-537 (1999)
  5. Alizadeh2000.pdf - Alizadeh et al., Nature 403:503-511 (2000)
  6. AlonPNAS.pdf - Alon et al., PNAS 96:6745-6750 (1999)
3/1/05
Suggested Reading
  1. AKT_regul_p27_NatMed02.pdf
  2. AKTphosphoryl_p27_NatMed02.pdf
  3. estrogens_p27_JBC03.pdf
  4. LongLiveFKHDs.pdf
  5. LymphomaCellCycle.pdf
  6. p27Haploinsuff.pdf
  7. p27Review_Science.pdf
  8. p27Review_Trends.pdf
  9. p57_SCF_PNAS03.pdf
3/8/05
Reading:
  1. Textbook, chapter 18, pages 647-696.
Additional Resources:
On-line glossaries:
  1. See page 734 of your textbook
Book:
  1. “Bioinformatics for Geneticists” by Michael R. Barnes and Ian C. Gray, 2003, John Wiley & Sons, Inc., Hoboken, NJ, 408 pp.
Exam on March 10.
Papers for presentations on March 24 will be available on March 10.

3/10/05
Papers for selection for presentations (part 1).
Please email to sruby@unm.edu (by Monday, March 14, 5 pm) your first and second choice of the article that you wish to present for the week of March 21, 2005.
  1. Bond_et_al_04.pdf - Bond, G.L., et al.  A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. 2004. Cell 119, pp. 591–602.
  2. Sweet-Cordaro_et_al_04.pdf - A. Sweet-Cordero et al An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis.  Nature Genetics  37, 48 - 55 (2004).
  3. Roepman_et_al_05.pdf - Roepman et al.  An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nature Genetics  37, 182 - 186 (2005)
  4. Lee_et_al_04.pdf - Lee et al.  Evidence for nucleosome depletion at active regulatory regions genome-wide.  Nature Genetics 36, 900 (2004)
  5. Rustici_et_al_04.pdf - Rustici et al.  Periodic gene expression program of the fission yeast cell cycle.  Nature Genetics 36, 810 (2004)
  6. Shyamsundar_et_al_05.pdf - Shyamsundar at al.  A DNA microarray survey of gene expression in normal human tissues.  Genome Biology 2005 6:R22
3/22/05
Reading:
  1. Chapter 2 (pp 15-39)
3/29/05
Reading:
  1. Chapters 4 and 5 of textbook
Lab problem will be handed out this Thursday and due Thursday, April 7.
YFG/P sequence handed out on Thursday, March 31.

3/31/05
Lab problem 3: Ruby_lab_problem_3.doc
YFG/P sequences: 05_YFG_Sequences_assign.doc
YFG problem: YFG_problem_05.rtf

4/7/04
Reading for labs on 04-07-05 and 04-14-05:
  1. Chapters 8 and 9
4/12/05
Required reading:
  1. Chapter 6 from Bioformatics and Functional Genomics
  2. Proteomics_rev.pdf - Zhu et al. (2003) Annu. Rev. Biochem. 72:783-812
  3. Functional_genomics_pro_1A00A.pdf - Bader et al. (2003) Trends Cell Biol. 13: 344-355
  4. Mass_spec_review.pdf - Aebersol and Mann (2003) Nature 422: 198-207 (rev.)
Highly recommended reading:
  1. Uetz_et_al_2-hybrid.pdf - Uetz et al. (2000) Nature 403: 623-627
  2. Ito_et_al_2-hybrid.pdf - Ito et al. (2001) Proc. Natl. Acad. Sci USA 98: 4569-4574
  3. Gavin_protein_interactions.pdf - Gavin et al. (2002) Nature 415:141-147
  4. Ho_protein_interactions.pdf - Ho et al. (2002) Nature 415:180-183
  5. SGA_analysis_Science.pdf - Tong et al. (2001) Science 294: 2364-2368
http://binddb.org: stores full descriptions of interactions, molecular complexes, and pathways



BMS516 Class Schedule
Week Day Date Instructor Lecture Lab Assignment Due
1 Tues 1/18/05 Ruby/Osley Intro to course/Intro to Genetics
Lecture_1_Osley_handouts.ppt
   
  Thur 1/20/05 Osley Intro to cell cycle
BMS516_1-20-05_handouts.ppt
BMS516_1-20-05_refs.ppt
Useful link:
(See reading assignment in announcements).
   
2 Tues 1/25/05 Osley/Atlas Genetic Approach- cell cycle regulatory genes
BMS516_1-25-05_Osley__7B653.ppt
BMS516_1-25-05_Osley_refs.ppt
Unix Tutorial
Matlab getstart.pdf
 
  Thur 1/27/05 Osley Genomic Approach -- cell cycle regulated genes
BMS516_1-27-05.ppt
BMS516_1-27-05_refs.ppt
(See reading assignment in announcements).
   
3 Tues 2/1/05 Atlas Clustering
BMS516_Lecture_020105.ppt
   
  Thur 2/3/05 Ness   Exper. Design (Gene Spring)
DataAnalysisLab.pdf
http://www.ncbi.nlm.nih.gov/projects/geo/
http://www.affymetrix.com/
 
4 Tues 2/08/05 Atlas Clustering
BMS516_Lecture_020105.ppt (cont.)
Clustering Lab
Lab3-PartI.pdf
accession.txt
cutaneous.txt
BittnerMelanoma.xls
(not necessary for lab:
 
  Thur 2/10/05 Atlas

Clustering Lab (cont.)
Lab3-PartII.pdf
Ness Lab Problem 1
5 Tues 2/15/05 Atlas Similarity measures/metrics and matrices
BMS516_Lecture_021505.ppt
   
  Thur 2/17/05 Atlas Classification
BMS516_lecture_021705.ppt
  Atlas Project 1
6 Tues 2/22/05 Atlas Algorithms/Genetic
BMS516_lecture_022205.ppt
   
  Thur 2/24/05

Run a genetic algorithm
Lab4.pdf
Lab4Worksheet.pdf
Lab4.zip (also in H:\Libclass\BMS516)
 
7 Tues 3/1/05 Ness   
Mammalian cdk's/ human genetic defects in cell cycle
Ness_CDK-CDKI.ppt

 
  Thur 3/3/05 Berwick Human genetics/epidemiology
Genetic%20Epidemiology_GEM.ppt
   
8 Tues 3/8/05 Ruby  lab_03-08-05_intro.ppt Human genome/diseases
Lab_3-08-05.pdf
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
http://130.192.70.30/huge/
Chi Square Table
Atlas Lab Problem 2
  Thur 3/10/05   Exam    
 --  -- 3/15-17/05   Spring Break    
9 Tues 3/22/05 Ruby Paper presentation
Rafael - Sweet-Cordaro_et_al_04.pdf
Sequence manipulation
lab_03-22-05_intro.ppt
03-22-05_Labv2.doc
Using%20GCG_BMS516_05.doc
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
 
  Thur 3/24/05 Students Paper presentations
David - Lee_et_al_04.pdf
Leyma - Shyamsundar_et_al_05.pdf
Jennifer - Bond_et_al_04.pdf
   
10 Tues 3/29/05 Ruby
Sequence comparison I
lab_03_29_05_intro.ppt
Lab_03-29_05.doc
http://www.ncbi.nlm.nih.gov/BLAST
 
  Thur 3/31/05 Ruby   Sequence comparison II
lab_03-31-05_intro.ppt
Lab_03-31-05_MSA.doc
http://us.expasy.org/tools/blast/
http://www.ebi.ac.uk/clustalw/
 
11 Tues 4/05/05 Ness Protein motifs/modifications
Ness_ProteinMotifs.ppt
 
  Thur 4/07/05 Ruby   Motif recognition
lab_04-07-05_intro.ppt
Lab_04-07-05.doc
http://www.expasy.org/tools/scanprosite
http://www.expasy.org/tools
http://www.ebi.ac.uk/interpro/scan.html
http://www.ebi.ac.uk/msd-srv/msdlite/apps/query
Ruby Lab Problem 3
12 Tues 4/12/05 Osley Protein-protein interactions
BMS516_4-12-05.ppt

 
  Thur 4/14/05 Ruby/Ness lab_04-14_05.ppt
Lab_04-14-05.doc
Protein structure
Spcdc2_pdb_structure.dat
view
1b38A.pdb
AAAa0Eaku.pdb
Sp_cdc2_fasta_pep.txt
p53_human_pep.txt
http://www.psipred.net
http://www.sdsc.edu/predictprotein
http://www.ncbi.nlm.nih.gov/BLAST
http://molvis.sdsc.edu/protexpl/frntdoor.htm
http://www.ncbi.nlm.nih.gov/Structure/

13 Tues 4/19/05 Ruby  lab_04-18-05_intro.ppt
Networks and pathways
Lab_04-18-05.doc
Ruby Lab Problem 4: from 4/7 
  Thur 4/21/05 Ruby  lab_04-20-05.ppt Upstream reg. regions
Lab_04-20-05.doc
http://www.ebi.ac.uk/clustalw/
cdc28_seqs_fasta_edit.txt
http://bioweb.pasteur.fr/seqanal/phylogeny/phylip-uk.html
Ruby Lab Problem 5: from 4/14
14 Tues 4/26/05 Ruby
  Open lab to finish YFG
YFG-P_hints.doc
longtine_et_al_98.pdf
Tasto_et_al_01.pdf
Project 2 -- YFG/P
  Thur 4/28/05 Ruby

Open lab to finish YFG
15 Tues 5/3/05 Students Paper presentations
Leyma Deharo
siRNA_mediated_gene_silencing.pdf
   
  Thur 5/5/05 Students Paper presentations
Jennifer Buntz
Allinen_etal_04_C_cell_microenvt_BC.pdf
  (5/6/05)
Project 3 -- YFG/P
    FINALS   NO Exam Entire website as a zip file 75Mb  
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Library 226 classroom schedule.