Design centering enables robustness screening of pattern formation models
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Motivation: Access to unprecedented amounts of quantitative biological data allows us to build and test biochemically accurate reaction-diffusion models of intracellular processes. However, any increase in model complexity increases the number of unknown parameters and, thus, the computational cost of model analysis. To efficiently characterize the behavior and robustness of models with many unknown parameters remains, therefore, a key challenge in systems biology. Results: We propose a novel computational framework for efficient high-dimensional parameter space characterization of reaction-diffusion models in systems biology. The method leverages the Lp-Adaptation algorithm, an adaptive-proposal statistical method for approximate design centering and robustness estimation. Our approach is based on an oracle function, which predicts for any given point in parameter space whether the model fulfills given specifications. We propose specific oracles to efficiently predict four characteristics of Turing-Type reaction-diffusion models: bistability, instability, capability of spontaneous pattern formation and capability of pattern maintenance. We benchmark the method and demonstrate that it enables global exploration of a model's ability to undergo pattern-forming instabilities and to quantify robustness for model selection in polynomial time with dimensionality. We present an application of the framework to pattern formation on the endosomal membrane by the small GTPase Rab5 and its effectors, and we propose molecular mechanisms underlying this system.
Details
Original language | English |
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Pages (from-to) | II134-II140 |
Journal | Bioinformatics |
Volume | 38 |
Issue number | 2 S |
Publication status | Published - 16 Sept 2022 |
Peer-reviewed | Yes |
External IDs
ORCID | /0000-0003-4414-4340/work/159608274 |
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PubMed | 36124805 |