Bioinformatics Analysis of the Early Inflammatory Response in a Rat Thermal Injury Model

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Bioinformatics Analysis of the Early Inflammatory Response in a Rat Thermal Injury Model

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dc.contributor.author Yang, Eric
dc.contributor.author Androulakis, Ioannis P
dc.contributor.author Maguire, Timothy
dc.contributor.author Yarmush, Martin Leon
dc.contributor.author Berthiaume, Francois
dc.date.accessioned 2011-04-26T04:20:51Z
dc.date.issued 2007
dc.identifier.citation Yang, Eric, Timothy Maguire, Martin L. Yarmush, Francois Berthiaume, and Ioannis P. Androulakis. 2007. Bioinformatics analysis of the early inflammatory response in a rat thermal injury model. BMC Bioinformatics 8: 10. en_US
dc.identifier.issn 1471-2105 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4875904
dc.description.abstract 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. Conclusion: 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. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1471-2105-8-10 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1797813/pdf/ en_US
dash.license LAA
dc.title Bioinformatics Analysis of the Early Inflammatory Response in a Rat Thermal Injury Model en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal BMC Bioinformatics en_US
dash.depositing.author Berthiaume, Francois
dc.date.available 2011-04-26T04:20:51Z
dash.affiliation.other HMS^Surgery-Massachusetts General Hospital en_US

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