Journal
GENOME RESEARCH
Volume 15, Issue 3, Pages 443-450Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.3124505
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Funding
- NCI NIH HHS [Z01 BC010593-02] Funding Source: Medline
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Genome-wide expression profiling of normal tissue may facilitate Our Understanding of the etiology of diseased organs and augment the development of new targeted therapeutics. Here, we have developed a high-density gene expression database of 18,927 unique genes for 158 normal human samples from 19 different organs of 30 different individuals using DNA microarrays. We report four main findings. First, despite very diverse sample parameters (e.g., age, ethnicity, sex, and postmortem interval), the expression profiles belonging to the same organs cluster together, demonstrating internal stability of the database. Second, the gene expression profiles reflect major organ-specific functions oil the molecular level, indicating consistency Of our database with known biology. Third, we demonstrate that any small (i.e., n similar to 100), randomly selected subset of genes can approximately reproduce the hierarchical clustering of the full data set, suggesting that the observed differential expression of >90% of the probed genes is of biological origin. Fourth, we demonstrate a potential application of this database to cancer research by identifying 19 tumor-specific genes in neuroblastoma. The selected genes are relatively underexpressed in all of the organs examined and belong to therapeutically relevant pathways, making them potential novel diagnostic markers and targets for therapy. We expect this database will be Of utility for developing rationally designed molecularly targeted therapeutics in diseases Such as cancer, as well as for exploring the functions of genes.
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