%0 Journal Article %J Bioinformatics (Oxford, England). 2011 Dec; 27(24):3407-14 %D 2011 %T A system-level approach for deciphering the transcriptional response to prion infection %A Mattia Zampieri %A Giuseppe Legname %A Daniel Segrè %A Claudio Altafini %X MOTIVATION: 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. %B Bioinformatics (Oxford, England). 2011 Dec; 27(24):3407-14 %I Oxford University Press %G en %U http://hdl.handle.net/1963/5745 %1 5600 %2 Mathematics %3 Functional Analysis and Applications %4 -1 %$ Submitted by Andrea Wehrenfennig (andreaw@sissa.it) on 2012-04-23T08:12:17Z\\nNo. of bitstreams: 1\\nZaLeSeAl11.pdf: 1229345 bytes, checksum: eb5500741d42ed30ef38112ebd4eae91 (MD5) %R 10.1093/bioinformatics/btr580 %0 Journal Article %J PLoS Comput Biol 2009;5(7): e1000420 %D 2009 %T Investigating the Conformational Stability of Prion Strains through a Kinetic Replication Model %A Mattia Zampieri %A Giuseppe Legname %A Claudio Altafini %X Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrPSc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils\\\' mean length) and is coherent with all experimental observations concerning strain-specific behavior. %B PLoS Comput Biol 2009;5(7): e1000420 %I PLoS %G en_US %U http://hdl.handle.net/1963/3989 %1 413 %2 Mathematics %3 Functional Analysis and Applications %$ Submitted by Andrea Wehrenfennig (andreaw@sissa.it) on 2010-08-11T10:35:47Z\\nNo. of bitstreams: 1\\njournal.pcbi.1000420.pdf: 468491 bytes, checksum: fda67b47ac16d98d11bc4ac879c17ec0 (MD5) %R 10.1371/journal.pcbi.1000420