Microarray Bioinformatics

This page intentionally left blank MICROARRAY BIOINFORMATICS This book is a comprehensive guide to all of the mathematics, statistics and computing you will need to successfully operate DNA microarray experiments. It is written for researchers, clinicians, laboratory heads and managers, from both biology and bioinformatics backgrounds, who work with or who intend to work with microarrays. The book covers all aspects of microarray bioinformatics, giving you the tools to design arrays and experiments, to analyze your data, and to share your results with your organisation or with the international community. There are chapters covering sequence databases, oligonucleotide design, experimental design, image processing, normalisation, identifying differentially expressed genes, clustering, classification and data standards. The book is based on the highly successful Microarray Bioinformatics course at Oxford University and, therefore, is ideally suited for teaching the subject at the postgraduate or professional level. Dov Stekel is Director of the Microarray Bioinformatics professional course at Oxford University and is a visiting academic at the Department of Biochemistry there. He also operates a bioinformatics consultancy, Bius, providing services to customers in the biotechnology industry and academia. Previously, he was the Manager of Bioinformatics at Ed Southern’s microarray company, Oxford Gene Technology, and has worked as a Bioinformatics Scientist at Glaxo Wellcome. Dov lives in London and is an avid chocolate maker. Microarray Bioinformatics DOV STEKEL Oxford University and Bius    Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge  , United Kingdom Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521819824 © Dov Stekel 2003 This book is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2003 - - ---- eBook (NetLibrary) --- eBook (NetLibrary) - - ---- hardback --- hardback - - ---- paperback --- paperback Cambridge University Press has no responsibility for the persistence or accuracy of s for external or third-party internet websites referred to in this book, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. To my parents, Zsuzsi and Ronnie Stekel In memory of Stephen Zatman, 1971–2002 Contents Foreword Preface ■ ■ ix xi Acknowledgments ■ xiii ■ 1 ■ 43 1 Microarrays: Making Them and Using Them 2 Sequence Databases for Microarrays 3 Computer Design of Oligonucleotide Probes 4 Image Processing 5 Normalisation 6 Measuring and Quantifying Microar