Clusters of adjacent and similarly expressed genes across normal human tissues complicate comparative transcriptomic discovery.

ABSTRACT

Transcriptomic techniques are valuable tools with which to validate genetic and biological hypotheses and are now widely available for research. However, with the exception of tumor biology, comparative genomics analyses have been difficult to use as discovery engines to describe biologically relevant expression changes. We propose that physical proximity of human genes correlates with similar mRNA expression, so that increased expression might include a disease-relevant gene and many other genes in the adjacent region. To increase the efficiency of combining susceptibility gene mapping and interpretation of transcriptomics, we developed a method to identify clusters of adjacent and similarly expressed genes. Gene expression profiles for 28,945 genes across 101 normal human tissues were obtained from the Gene Logic BioExpress system. The expression similarity for genes in sliding-windows was measured using average pair-wise Pearson correlation coefficients. We identified 187 clusters (p < 10e-4) of co-regulated genes, including 2648 genes, or 9.1% of all genes considered and termed these "clusters of adjacent and similarly expressed genes" (CASEGs). Genes in 15 (8.2%) of these clusters demonstrate a significant co-expression enrichment (p < 10e-10). This study demonstrates the coordinate expression of neighboring genes and provides a comprehensive view of expression-based compartmentalization of the human genome, which can be overlaid on genetic susceptibility gene maps.