Foreword

The impact of microarray measurements on biology and bioinformatics has been astounding. Starting from virtually no literature a few years ago, this field has come to dominate many conferences and journals. As an example, the Intelligent Systems for Molecular Biology conference, the annual meeting of the International Society for Computational Biology held in Copenhagen in 2002, had almost 50% of its papers in the areas addressed directly or indirectly within this book. Four years ago, there were none. Bioinformatics has always been driven by the availability of data—sequential, structural, and most recently functional. The availability of sequence data brought into biology a cadre of computer scientists with special skills in string processing. The availability of structural data brought in technical experts in visualization and computational geometry. This most recent development—the availability of relatively large data sets measuring the expression of genes within cells—has helped attract yet another group of scientists—the data miners, machine learners and statisticians.

In many ways, the impact of this data on biology and informatics can be summarized in figure 1.4 of this book—the world has not quite been turned upside down, but it certainly has been turned on its side! A decade ago, if confronted with the data matrix shown on the right of this figure, a well-trained information scientist would say "This is ridiculous. Why would you ask me to analyze a data set where you clearly have a profoundly under-determined problem? There's not enough data here to distinguish between any of the zillion hypotheses that could be consistent with this data set. And who designed these experiments, anyway? How can you measure so many features of such a few examples?" Yet, these experiments are proceeding and are making major contributions to our understanding of how gene systems interact, how to distinguish different types of cancer, and how to measure the impact of the environment on a cell. Our information scientist friend is, in some sense, correct about the relative paucity of data. (Have you ever tried to convinced a biologist holding a microarray with 45,000 spots that this is a relatively data-poor exercise? It's not fun.) However, the information scientist has missed the point about the design and analysis of these experiments. These data sets do indeed contain gold, but the experiments (as for all experiments) must be considered carefully in both the design and implementation phases in order to maximize value. This is where the authors of this book have made a contribution. They start from the premise that these experiments offer great potential, but must be performed and analyzed carefully. They set the context of traditional reductionist biology, and then go on to discuss the design, analysis, storage and interpretation of this first generation of functional genomics experiments. The writing is lively and candid, and the examples are taken from an array of applications. The authors' practical experience in dealing with this data comes through, and they intersperse practical advice with philosophical reverie. Sometimes, these two merge into important discussions such as on the role of ontologies in making sense of these data sets, or on the challenges of linking microarray results with phenotypic data pertinentto human disease.

The functional genomics revolution is here. We do not knowhow it will change our view of biology and medicine. They are both much more likely to become quantitative and systematic (as opposed to qualitative and reductionist). The informatics techniques required to address this revolution are not entirely clear, but this text gets us started in the right direction.

Russ Altman

Stanford University

March 2002

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