Obiettivo In systems biology, we aim at deriving gene-regulatory or signaling models based on multivariate readouts, thereby generating predictions for novel experiments. However any model only approximates reality, leaving out details or other types of regulation. Here I ask why a given model fails to predict a set of observations with acceptable accuracy and how to refine the model using this experimental knowledge. This resembles a question from signal processing, namely the blind identification of hidden (latent) variables in a mixing model. Many, powerful methods have been proposed to answer it. However, they have not been extended to dynamical systems due to the involved strong nonlinearities.I propose to infer additional upstream species in a given model, denoted as latent causes, that improve the prediction and at the same time are subject to the model dynamics. Multiple causes are estimated using statistical assumptions such as minimum mutual information. The model estimation will be performed within a Bayesian framework. This will allow for the efficient but crucial inclusion of prior biological information. The method will be applied to infer a differentiation model describing lineage segregation of embryonic stem (ES) cells to endo- and mesoderm. Here, latent causes are known to be transcription factors and microRNAs, but also small molecules/drugs. Identified off-target effects of these causes will be validated in collaboration with experimental partners.This study will establish links between information-theoretic signal processing and dynamical systems. Its application to a detailed ES cell model will foster our understanding of differentiation and may ultimately contribute to the development of more efficient differentiation protocols for cell replacement therapy. Campo scientifico engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsignal processingnatural sciencesmathematicsapplied mathematicsdynamical systems Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-PE7 - ERC Starting Grant - Systems and communication engineering Invito a presentare proposte ERC-2010-StG_20091028 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Coordinatore HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Contributo UE € 1 238 590,00 Indirizzo Ingolstadter landstrasse 1 85764 Neuherberg Germania Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Ricercatore principale Fabian Theis (Prof.) Contatto amministrativo Juergen Ertel (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Germania Contributo UE € 1 238 590,00 Indirizzo Ingolstadter landstrasse 1 85764 Neuherberg Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Ricercatore principale Fabian Theis (Prof.) Contatto amministrativo Juergen Ertel (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato