Objective 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. Fields of science engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsignal processingnatural sciencesmathematicsapplied mathematicsdynamical systems Programme(s) 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) Topic(s) ERC-SG-PE7 - ERC Starting Grant - Systems and communication engineering Call for proposal ERC-2010-StG_20091028 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH EU contribution € 1 238 590,00 Address Ingolstadter landstrasse 1 85764 Neuherberg Germany See on map Region Bayern Oberbayern München, Landkreis Activity type Research Organisations Principal investigator Fabian Theis (Prof.) Administrative Contact Juergen Ertel (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Germany EU contribution € 1 238 590,00 Address Ingolstadter landstrasse 1 85764 Neuherberg See on map Region Bayern Oberbayern München, Landkreis Activity type Research Organisations Principal investigator Fabian Theis (Prof.) Administrative Contact Juergen Ertel (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data