The functional genomics "meltdown" is coming. At least that is what we fear is likely to occur with the confluence of the high expectations engendered by the Human Genome Project and the prevalence of highly uneven scholarship in the investigations made possible by comprehensive genomic measurement technologies, such as microarray-based expression profiling. Because the availability of these technologies has preceded the development of a substantive canon of appropriate analytic techniques, safe experimental design, and cautionary tales, the quality of these investigations and the manner in which they have been reported often results in the dissemination of highly preliminary and flimsy findings. The absence of widespread use of computational and biological validation procedures associated with these studies has led to many reports that will likely not be substantiated by follow-up studies. With the rapid decrease in the cost of genomic techniques, follow-up studies are likely to arise within the next few years. At that time, several previously well-publicized findings in basic biology, clinical diagnosis, clinical prognosis, and pharmacogenomic targeting will be found deficient. The inevitable reaction to these unfortunate developments will be attenuated if the discipline of functional genomics has matured enough by then to achieve the rigor required.

In this book, we have attempted to address some of the challenges required to begin this maturational process in the intersection between microarray expression technology, bioinformatics, and biomedical science. Despite the likelihood of an eventual disappointment and subsequent retrenchment of the ambitions of microarray applications, we are confident that the development of systematic approaches to this discipline will ultimately deliver on the exuberant predictions and promises made over the last 5 years. We hope that our experience (including our own generous share of mistakes), as communicated here, will help provide the reader with a framework to participate productively in attaining this goal.

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