TRANSCRIPTOME 2002: From Functional Genomics to Systems
Characterizing Transcriptional Determinants of the Innate Immune Response to Infection Through Gene Expression and Literature Profiling
Damien Chaussabel, Roshanak Semnani, Mary Ann McDowell, David L Sacks, Alan Sher, Thomas B Nutman, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
New perspectives for the study of host-pathogen interactions have emerged from the recent development of microarray technologies that allow genome wide measures of gene expression. We used high-density oligonucleotide arrays to monitor changes in gene expression that occur following exposure of human Macrophages and dendritic cells to a wide diversity of infectious agents. An approach was developed for the extraction of meaningful knowledge from the large volume of information generated by this type of experiment in which the transcriptional events taking place during the early response to infection were characterized by sequentially mining the information contained in this expression dataset and the literature. Clustering analysis of expression data revealed complex profiles and allowed to identify groups of tightly co-regulated genes. An original literature profiling technique based on the clustering analysis of term occurrences in abstracts was then used to scan scientific publications for the existence of functional relationships among genes sharing similar expression profiles. This approach allowed us to identify groups of genes associated from both functional and transcriptional standpoint. Interestingly pathogen-specific responses were found to be constituted by unique combinations of these transcriptional determinants, with dramatic differences being observed between the two types of professional antigen presenting cells studied.
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