Feature Finding Title
Featured Finding Figure
Gene expression profiling holds great promise for identifying molecular pathologies of central nervous system disorders. However, the analysis of brain tissue poses unique challenges, as typical gene microarray signals represent averaged transcript levels across neuronal and glial cell populations. We show that ratios of gene transcript levels between gray (GM) and adjacent white matter (WM) samples can be used to estimate the relative glial and neuronal cellular origins of expression, and are conserved in the human and mouse brains. WM/GM ratios for large number of genes were significantly correlated across different areas of the human (~17,000 genes) or mouse brain; human/mouse ~6,100 orthologous genes; mouse/ mouse (~21,000 genes)[Top graphs and bottom color-coded correlations tables; Axis values indicate Log2(WM/GM)]. We show that incorporating these ratios into transcriptome analysis i) provides new analytical perspectives, ii) increases the potential for biological insight obtained from postmortem transcriptome studies, iii) expands knowledge about glial and neuronal cellular programs, and iv) facilitates the generation of cell-type specific hypotheses. This approach represents a robust and cost-effective "add-on" to transcriptome analyses of the mammalian brain and can be applied post-hoc to equivalent mouse and human brain datasets.
Sibille E, Arango V, Joeyen-Waldorf J, Wang Y, Leman S, Surget A, Belzung C, Mann JJ, Lewis DA: Large-scale estimates of cellular origins of mRNAS: enhacing the yield of transcriptome analyses. J Neurosci Methods 167: 198-206, 2008.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
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