DNA Microarrays and Gene Expression: From Experiments to Data Analysis and Modeling

by Pierre Baldi , G. Wesley Hatfield

• ISBN13: 9780521800228
• ISBN10: 0521800226
• Format: Hardcover
• Copyright: 2002-09-30
• Publisher: Cambridge University Press

Summary

Massive data acquisition technologies, such as genome sequencing, high-throughput drug screening, and DNA arrays are in the process of revolutionizing biology and medicine. Using the mRNA of a given cell, at a given time, under a given set of conditions, DNA microarrays can provide a snapshot of the level of expression of all the genes in the cell. Such snapshots can be used to study fundamental biological phenomena such as development or evolution, to determine the function of new genes, to infer the role individual genes or groups of genes may play in diseases, and to monitor the effect of drugs and other compounds on gene expression. This inter-disciplinary introduction to DNA arrays will be essential reading for both biology and computer science researchers wanting to take advantage of this powerful new technology.

Table of Contents

Preface	viii
A brief history of genomics	1	(6)
DNA array formats	7	(10)
In situ synthesized oligonucleotide arrays	7	(4)
Pre-synthesized DNA arrays	11	(1)
Filter-based DNA arrays	12	(1)
Non-conventional gene expression profiling technologies	13	(4)
DNA array readout methods	17	(12)
Reading data from a fluorescent signal	17	(4)
Reading data from a radioactive signal	21	(8)
Gene expression profiling experiments: Problems, pitfalls, and solutions	29	(24)
Primary sources of experimental and biological variation	29	(3)
Special considerations for gene expression profiling in bacteria	32	(10)
Problems associated with target preparation with polyadenylated mRNA from eukaryotic cells	42	(2)
A total RNA solution for target preparation from eukaryotic cells	44	(1)
Target cDNA synthesis and radioactive labeling for pre-synthesized DNA arrays	45	(1)
Data acquisition for nylon filter experiments	45	(3)
Data acquisition for Affymetrix GeneChip™ glass slide experiments	48	(1)
Normalization methods	49	(4)
Statistical analysis of array data: Inferring changes	53	(20)
Problems and common approaches	53	(2)
Probabilistic modeling of array data	55	(10)
Simulations	65	(4)
Extensions	69	(4)
Statistical analysis of array data: Dimensionality reduction, clustering, and regulatory regions	73	(24)
Problems and approaches	73	(2)
Visualization, dimensionality reduction, and principal component analysis	75	(3)
Clustering overview	78	(4)
Hierarchical clustering	82	(3)
K-means, mixture models, and EM algorithms	85	(5)
DNA arrays and regulatory regions	90	(7)
The design, analysis, and interpretation of gene expression profiling experiments	97	(38)
Experimental design	99	(1)
Identification of differentially expressed genes	100	(1)
Determination of the source of errors in DNA array experiments	101	(2)
Estimation of the global false positive level for a DNA array experiment	103	(6)
Improved statistical inference from DNA array data using a Bayesian statistical framework	109	(1)
Nylon filter data vs. Affymetrix GeneChip™ data	109	(15)
Modeling probe pair set data from Affymetrix GeneChips™	124	(1)
Application of clustering and visualization methods	124	(1)
Identification of differential gene expression patterns resulting from two-variable perturbation experiments	125	(10)
Systems biology	135	(42)
Introduction	135	(2)
The molecular world: Representation and simulation	137	(9)
Computational models of regulatory networks	146	(17)
Software and databases	163	(2)
The search for general principles	165	(12)
Appendix A Experimental protocols	177	(8)
Appendix B Mathematical complements	185	(10)
Appendix C Internet resources	195	(4)
Appendix D Cyber T: An online program for the statistical analysis of DNA array data	199	(8)
Index	207