P06 – The Timeline of Genomic Response to Burn Injury

Author(s):
Celeste Finnerty, Xueling Li, Bernard Fongang, Padma Nainar, Nicole Gibran, Richard Gamelli, Andrzej Kudlicki, David Herndon, University of Texas Medical Branch

Background: The timeline of genomic response following burn injury may provide important information for refining therapeutic interventions during acute and rehabilitative stages. Time-series microarrays can capture dynamic profiles of the genome-wide gene expression.

Hypothesis: Clustering the gene expression profiles according to the temporal response patterns will reveal the timing of the functionally related burn response genes. Also, considering the age and sex effects is expected to significantly improve the statistical capability in identifying genes response to burns.

Methods: We obtained time-dependent gene expression profiles from peripheral blood leukocytes from burn patients 7-99 years old. The data were corrected for age and sex using expression profiles from control patients that were modeled using our generic linear model. After removing the age and sex specific effects on the gene expression in burn patients, we applied smoothing with moving median and subsequent hierarchical clustering to the burn time-course series.

Results: Five distinct groups of the burn response genes were revealed by clustering the gene expression profiles on 0-39 post burn days according to the time-dependent response patterns. The five groups of the burn response genes are significantly enriched in distinct functions including immunity, metabolism, infection and wound healing. Three critical gene expression transitional timing points occur at approximately 3, 11, and 33 days post burn. Three interesting functional groups of genes correspond to temporal regulation. Metabolic genes are elevated between 1.5 – 11 days post burn. Immune genes are down regulated 3 – 33 days post burn. On the contrary, genes demonstrating a response to infection are up-regulated 3-33 days post burn. Genes involved in healing are modulated 3-33 days post burn as well.

Conclusions: The timing of expression of different groups of genes identified by our approach reflects the distinct functions occurring in response to burn injury. Correcting for age and sex significantly improves the statistical accuracy in identifying genes response to burns.