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Gene Expression Profiling as a Window into Idiopathic Pulmonary Fibrosis Pathogenesis

Can We Identify the Right Target Genes?

Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Naftali Kaminski, M.D., Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, NW 628 MUH, 3459 5th Avenue, Pittsburgh, PA 15261. E-mail: kaminskin{at}upmc.edu

ABSTRACT

Expression microarrays that provide genome-level, transcriptional, high-resolution profiles have been applied successfully to multiple diseases. Although microarrays provide information regarding thousands of genes, many investigators prefer to focus on a single gene and validate its role, an approach often supported by grant and journal reviewers. Only a minority of investigators focus on global changes in gene expression. Here, we describe and contrast two general approaches to the use of microarray data: the reductionist "cherry picking" approach and the more global, quantitative "systems" approach. We describe microarray analysis experiments relevant to idiopathic pulmonary fibrosis (IPF) in the context of these two approaches. Although it seems that the cherry-picking approaches have been successful in identifying new relevant genes in IPF, we suggest that to fulfill the discovery potential of microarrays in IPF and to create a working model of IPF, unbiased integrative systems approaches are required.

Key Words: FIZZ1 • matrix metalloprotease • microarrays • osteopontin • systems biology

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