Parameter-free methods distinguish Wnt pathway models and guide design of experiments

• DOI: 10.1073/pnas.1416655112
• Publication Date: 2015-02-18T04:44:40Z
• Authors: Adam L. MacLean; Zvi Rosen; Helen M. Byrne; Heather A. Harrin...
• Keywords: Adult; 0301 basic medicine; Molecular Networks (q-bio.MN); Bayesian inference; 0206 medical engineering; 02 engineering and technology; Quantitative Biology - Quantitative Methods; Models, Biological; Mathematics - Algebraic Geometry; 03 medical and health sciences; Models; FOS: Mathematics; Animals; Humans; Quantitative Biology - Molecular Networks; Wnt Signaling Pathway; Algebraic Geometry (math.AG); Quantitative Methods (q-bio.QM); Biological; Experimental design; Matroids; Chemical Reaction Network Theory; FOS: Biological sciences; Bistability

Significance The canonical Wnt/β-catenin signaling pathway is important for essential cellular functions and implicated in many diseases. We introduce a new mathematical model that focuses on β-catenin degradation protein shuttling between compartments. compare our to others show all fit time-dependent experimental data. To evade this parameter problem, we use algebraic methods characterize features are independent of the choice values. find multiple responses Wnt feasible under certain conditions model, but not others; moreover, provide dependencies species (variables) inform future experiments discrimination. also highlight wide applicability these tools across problems systems biology.