Bioinformatics analysis of the early inflammatory response in a rat thermal injury model.
BACKGROUND
Thermal injury is among the most severe forms of trauma and its effects are both local and systemic. Response to thermal injury includes cellular protection mechanisms, inflammation, hypermetabolism, prolonged catabolism, organ dysfunction and immuno-suppression. It has been hypothesized that gene expression patterns in the liver will change with severe burns, thus reflecting the role the liver plays in the response to burn injury. Characterizing the molecular fingerprint (i.e., expression profile) of the inflammatory response resulting from burns may help elucidate the activated mechanisms and suggest new therapeutic intervention. In this paper we propose a novel integrated framework for analyzing time-series transcriptional data, with emphasis on the burn-induced response within the context of the rat animal model. Our analysis robustly identifies critical expression motifs, indicative of the dynamic evolution of the inflammatory response and we further propose a putative reconstruction of the associated transcription factor activities.


RESULTS
Implementation of our algorithm on data obtained from an animal (rat) burn injury study identified 281 genes corresponding to 4 unique profiles. Enrichment evaluation upon both gene ontologies and transcription factors, verifies the inflammation-specific character of the selections and the rationalization of the burn-induced inflammatory response. Conducting the transcription network reconstruction and analysis, we have identified transcription factors, including AHR, Octamer Binding Proteins, Kruppel-like Factors, and cell cycle regulators as being highly important to an organism's response to burn response. These transcription factors are notable due to their roles in pathways that play a part in the gross physiological response to burn such as changes in the immune response and inflammation.


CONCLUSIONS
Our results indicate that our novel selection/classification algorithm has been successful in selecting out genes with play an important role in thermal injury. Additionally, we have demonstrated the value of an integrative approach in identifying possible points of intervention, namely the activation of certain transcription factors that govern the organism's response.
Yang
Eric
E
Biomedical Engineering Department, Rutgers University, Piscataway, NJ, USA. eyang@eden.rutgers.edu <eyang@eden.rutgers.edu>
Maguire
Timothy
T
Yarmush
Martin L
ML
Berthiaume
Francois
F
Androulakis
Ioannis P
IP
D000465:Algorithms; D000818:Animals; D002056:Burns; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006358:Hot Temperature; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors