01822nas a2200145   4500008004100000245009200041210006900133260002800202520132600230100002101556700002201577700001901599700002201618856003601640       2011                        en  d00aA system-level approach for deciphering the transcriptional response to prion infection0 asystemlevel approach for deciphering the transcriptional respons  bOxford University Press3 aMOTIVATION: Deciphering the response of a complex biological system to an insulting event, at the gene expression level, requires adopting theoretical models that are more sophisticated than a one-to-one comparison (i.e. t-test). Here, we investigate the ability of a novel reverse engineering approach (System Response Inference) to unveil non-obvious transcriptional signatures of the system response induced by prion infection.\\r\\nRESULTS: To this end, we analyze previously published gene expression data, from which we extrapolate a putative full-scale model of transcriptional gene-gene dependencies in the mouse central nervous system. Then, we use this nominal model to interpret the gene expression changes caused by prion replication, aiming at selecting the genes primarily influenced by this perturbation. Our method sheds light on the mode of action of prions by identifying key transcripts that are the most likely to be responsible for the overall transcriptional rearrangement from a nominal regulatory network. As a first result of our inference, we have been able to predict known targets of prions (i.e. PrP(C)) and to unveil the potential role of previously unsuspected genes.\\r\\nCONTACT: altafini@sissa.it\\r\\nSUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.1 aZampieri, Mattia1 aLegname, Giuseppe1 aSegrè, Daniel1 aAltafini, Claudio  uhttp://hdl.handle.net/1963/5745