Gene Expression Profile Analysis by DNA Microarrays: Promise and Pitfalls

• Published in: JAMA : the journal of the American Medical Association Vol. 286; no. 18; pp. 2280 - 2288
• Main Authors: King, Hadley C, Sinha, Animesh A
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 14-11-2001
• Subjects: Biological and medical sciences; Biology; Computerized, statistical medical data processing and models in biomedicine; Computers; Deoxyribonucleic acid; DNA; Gene Expression Profiling - methods; General aspects. Methods; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic Variation; Genetics; Humans; Medical research; Medical sciences; Oligonucleotide Array Sequence Analysis; Pathology; Reference Values; Human; DNA chip; Review; Gene expression; Genetic determinism; Computer science; Polymerase chain reaction; Technology; Genetics; Adult; Critical study; Molecular biology; Computer aided analysis
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.286.18.2280

DNAmicroarrays represent a technological intersection between biology
and computers that enables
gene expression analysis in human tissues on a
genome-wide scale. This application can be expected to prove extremely valuable
for the study of the
genetic basis of complex diseases. Despite the enormous
promise of this revolutionary technology, there are several issues and possible
pitfalls that may undermine the authority of the microarray platform. We discuss
some of the conceptual, practical, statistical, and logistical issues surrounding
the use of microarrays for gene expression profiling. These issues include
the imprecise definition of normal in expression
comparisons; the cellular and subcellular heterogeneity of the tissues being
studied; the difficulty in establishing the statistically valid comparability
of arrays; the logistical logjam in analysis, presentation, and archiving
of the vast quantities of data generated; and the need for confirmational
studies that address the functional relevance of findings. Although several
complicated issues must be resolved, the potential payoff remains large.