BIOSTATISTICS 140.688:   STATISTICS FOR GENE EXPRESSION
CLASS SCHEDULE and READING LIST, SPRING 2002

A detail from Paul Cézanne's "Pommes et biscuits"  1879-1882, from the Musée de l'Orangerie, Paris.
Cézanne was a precursor of expressionism in more ways than it is sometimes realized....


March 25     OVERVIEW OF THE COURSE

Discussion of the logistics of the class, exam policy, software suggestions, overview of the schedule.
Open discussion on additional topics that should be covered.

Gene Expression, Speed T  Wald Lecture 2001 presentation materials

Nature Genetics Special Issue: the Chipping Forecast

Microarray Data Analysis  J Quackenbush  presentation materials

Introduction to genome biology and DNA microarray experiments  Gentlemen R Dudoit S  presentation materials



 

March 27 cDNA ARRAY TECHNOLOGY  (Qin Bin Guo, JHU) 


Overview of the basic biological principles behind gene expression microarray measurements and the steps involved in carrying out a gene expression experiment. 

A Concise Guide to cDNA Microarray Analysis
Hegde P, Qi R, Abernathy R, Gay C, Dharap S, Gaspard R, Earle-Hughes J, Snesrud E, Lee NH, and Quackenbush J 
Biotechniques (2000), 29(3):548-562     Link to PDF and html versions

Expression profiling using cDNA microarrays. 
Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM 
Science 1999 Jan 1;283(5398):83-7     Article(PDF) 



 

April 1 OLIGONUCLEOTIDE ARRAYS MODEL--BASED EXPRESSION INDICES (Rafael Irizarry, JHU) 


Overview of the data structures associated with oligonucleotide arrays, and procedures for normalization and quality control. Comparison of methods for the derivation of expression indices from probe--level data. It includes the Li--Wong method implemented in D-chip, the approaches used in the Affymetrix software and the library affy in R

Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
Cheng Li and Wing Hung Wong
PNAS 98: 31-36dChip Homepage including download info, and PNAS reference

Exploration, Normalization, and Summaries of High Density Oligonucleotide Array Probe Level Data.
Irizarry, RA, et. al.  Manuscript in preparation. [Full text-PDF] 
The affy library in R Homepage including download info

GeneLogic workshop on Low-Level analysis of Affymetrix GeneChip data  Presentation materials



 

April 3 NORMALIZATION 


Overview of methods and software for the normalization of microarray data.

cDNA microarray experiments: preprocessing and experimental design  Gentlemen R Dudoit S  presentation materials

Ratio-based decisions and the quantitative analysis of cDNA micro-array images
Chen Y, Dougherty E, Bittner M
Journal of Biomedical Optics 2:364 (1997)     Article(PDF)

Normalization for cDNA Microarray Data 
Y. H. Yang, S. Dudoit, P. Luu and T. P. Speed. 
UC Berkeley Tech Report December 2000     Abstract, Full text and Powerpoint presentation

SNOMAD  software Standardization and Normalization of Microarray data.

Tutorial on the Loess curve--fitting approach.



 

April 8   MORE ON NORMALIZATION AND THE NEED FOR REPLICATION 


Illustration of sma library for normalization. Discussion of reproducibility of microarray experiments and its implication for the design and interpretation of array experiments.

SMA  R library Normalization of Microarray data, and more. 
Braju version of SMA  R library Normalization of Microarray data, and more. 

R commands used in class

Importance of replication in microarray gene expression studies: Statistical methods and evidence from repetitive cDNA hybridizations
Lee ML, Kuo FC, Whitmore GA, Sklar J.
Proc Natl Acad Sci U S A 2000 Aug 29;97(18):9834-9839    Article(PDF)



 

April 10 IDENTIFYING GENES THAT ARE DIFFERENTIALLY EXPRESSED ACROSS TWO TISSUE TYPES


Discussion of approaches for establishing whether genes that are differentially expressed across two samples or two groups of samples.

Development of a prostate cDNA microarray and statistical gene expression analysis package
Carlisle AJ, Prabhu VV, Elkahloun A, Hudson J, Trent JM, Linehan WM, Williams ED, Emmert-Buck MR, Liotta LA, Munson PJ, Krizman DB
Mol Carcinog 2000 May;28(1):12-22     Article(PDF)

Significance Analysis of Microarrays
Tusher, Tibshirani and Chu (2001) PNAS  [Full text postscript]  SAM Software

Determining Significant Fold Differences in Gene Expression Analysis
Butte AJ, Ye J, Niederfellner G, Rett K, Häring HU, White MF, Kohane IS
Pacific Symposium on Biocomputing 2001; 6:6-17    Article(PDF)



 

April 15 MULTILEVEL MODELING OF MICROARRAY DATA


Introduction to multilevel modeling for describing the variabiilty of gene expression ratios across the genome. 

On differential variability of expression ratios: Improving statistical inference about gene expression changes from microarray data.
Newton, M.A., C.M. Kendziorski, C.S. Richmond, F.R. Blattner, and K.W. Tsui 
Journal of Computational Biology to appear     Article(PDF)

Microarrays, Empirical Bayes Methods, and False Discovery Rates.
Bradley Efron, John Storey, and Robert Tibshirani
Tech report to appear     Article(PDF)

A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inference of gene changes.
Baldi, P and Long AD
Bioinformatics   Article(PDF)

Cyber-T   Bayesian analysis of two-group Microarray data.



 

April 17 SAMPLE SIZE 


Approaches for determining the number of replications in the design of microarray experiments. 


 

April 22 ANALYSIS OF VARIANCE MODELS  FOR MICROARRAYS


Using principles of DOE (design of experiments) to improve microarray analyses.

Design and Analysis of Gene Expression Microarray Experiments 
Kerr K, Churchill, G
Article, Presentation slides and Supplementary materials by Ulrich Mansmann



 

April 24    VISUALIZATION OF MICROARRAY DATA


Approaches to the visualization of gene expression patterns, including basic hierarchical clustering and dendrogram construction.

Cluster analysis and display of genome-wide expression patterns
M.B. Eisen, P.T. Spellman, P.O. Brown, David Botstein
PNAS Vol. 95, Issue 25, 14863-14868, December 8, 1998     Article(PDF)

The transcriptional program in the response of human fibroblasts to serum. 
Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JCF, Trent JM, Staudt LM, Hudson J Jr, Boguski MS, Lashkari D, Shalon D, Botstein D, Brown PO 
Science 1999 Jan 1;283(5398):83-7     Article(PDF)

Computational analysis of microarray data. Quackenbush, J
Nature Reviews Genetics,  2, 418-427 (2001)   Full text

Clustering in an Object-Oriented Environment
Anja Struyf, Mia Hubert, and Peter Rousseeuw 
JSS Article(PDF) and more

Examples of cluster Analysis in R

Peter Rousseeuw, Anja Struyf and Mia Hubert
R Functions for cluster analysis
CRAN websiteDownload and User Manual



 

Apr 29 PRINCIPAL COMPONENT ANALYSIS


Introduction to principal component analysis, its interpratation, and its limitations.

Tutorial on Principal Components Analysis     Link



 

May 1  BINARY CLASSIFICATION


A whilrlwind introduction to binary classification in statistics and artificial intelligence. 

A Tutorial on Logistic Regression
Y So
SAS tutorialArticle(PDF)

Stat Soft documentation and tutorial on discriminant analysis.
Stat Soft documentation and tutorial on classification trees.

Classification
R J Henery
Machine Learning, Neural and Statistical Classification   Chapter (PS)

Flexible discriminant analysis by optimal scoring 
Hastie, T., Tibshirani, R. & Buja, A. 
Journal of the American Statistical Association (1994) 89: 1255-1270 

Data Mining Class Notes
D. Madigan

Machine Learning of Rules and Trees 
C Feng, D Michie
Machine Learning, Neural and Statistical Classification  Chapter (PS)



 

May 6  COMPARISON OF CLASSIFIERS 


Comparison of alternative approaches to binary classification.

Methods of Comparison for classifiers
R J Henery
Machine Learning, Neural and Statistical Classification   Chapter (PS)

Comparison of Discrimination Methods for the Classification of Tumors Using Gene Expression Data 
S. Dudoit, J. Fridlyand, and T. P. Speed 
UC Berkeley Tech Report June 2000    Presentation slides  Article(PDF)



 

May 8 CASE STUDIES IN MOLECULAR CLASSIFICATION OF CANCER: I


Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling 
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM, et al. 
Nature 2000 Feb 3;403(6769):503-11    Article(PDF)

Molecular Classification of Cutaneous Malignant Melanoma by Gene Expression Profiling. 
M. Bittner, P. Meltzer, Y. Chen, Y. Jiang, E. Seftor, M. Hendrix, M. Radmacher, R. Simon, Z. Yakhini, A. Ben-Dor, E. Dougherty, E. Wang, F. Marincola, C. Gooden, J. Lueders, A. Glatfelter, P. Pollock, E. Gillanders, D. Leja, K. Dietrich, C., M. Berens, D. Alberts, V. Sondak, N. Hayward, and J. Trent 
Nature 406: 536-540 (2000)     Article(PDF) Supplemental Information



 

May 13 CASE STUDIES IN MOLECULAR CLASSIFICATION OF CANCER: II


Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.
Bhattacharjee et al, PNAS  November 13, 2001  [Full Text]

Diversity of gene expression in adenocarcinoma of the lung
Garber etal PNAS  November 13, 2001  [Full Text]

AutoClass  Unsupervised classification



 

May 15 INTRODUCTION TO BIOCONDUCTOR MICROARRAY LIBRARIES IN R


Bioconductor Project