Reference : Using Regularization to Infer Cell Line Specificity in Logical Network Models of Sign...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Using Regularization to Infer Cell Line Specificity in Logical Network Models of Signaling Pathways.
De Landtsheer, Sébastien mailto [> >]
Lucarelli, Philippe mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Life Science Research Unit]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Frontiers in physiology
[en] clustering ; logical model ; network model ; optimization ; regularization ; sparsity
[en] Understanding the functional properties of cells of different origins is a long-standing challenge of personalized medicine. Especially in cancer, the high heterogeneity observed in patients slows down the development of effective cures. The molecular differences between cell types or between healthy and diseased cellular states are usually determined by the wiring of regulatory networks. Understanding these molecular and cellular differences at the systems level would improve patient stratification and facilitate the design of rational intervention strategies. Models of cellular regulatory networks frequently make weak assumptions about the distribution of model parameters across cell types or patients. These assumptions are usually expressed in the form of regularization of the objective function of the optimization problem. We propose a new method of regularization for network models of signaling pathways based on the local density of the inferred parameter values within the parameter space. Our method reduces the complexity of models by creating groups of cell line-specific parameters which can then be optimized together. We demonstrate the use of our method by recovering the correct topology and inferring accurate values of the parameters of a small synthetic model. To show the value of our method in a realistic setting, we re-analyze a recently published phosphoproteomic dataset from a panel of 14 colon cancer cell lines. We conclude that our method efficiently reduces model complexity and helps recovering context-specific regulatory information.
Researchers ; Professionals
H2020 ; 642295 - MEL-PLEX - Exploiting MELanoma disease comPLEXity to address European research training needs in translational cancer systems biology and cancer systems medicine
FnR ; FNR7643621 > Thomas Sauter > > Predicting individual sensitivity of malignant melanoma to combination therapies by statistical and network modeling on innovative 3D organotypic screening models > 01/05/2015 > 30/04/2018 > 2013

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