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Modeling of 2D diffusion processes based on microscopy data: parameter estimation and practical identifiability

Sabrina Hock, Jan Hasenauer, Fabian J Theis

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    Summary
    This summary is machine-generated.

    This study introduces a new method to analyze diffusion processes from microscopy images, improving parameter estimation and uncertainty quantification for biological models. The approach offers more rigorous bounds than traditional methods.

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    Area of Science:

    • Quantitative Biology
    • Biophysics
    • Systems Biology

    Background:

    • Diffusion is crucial for biological processes like chemotaxis and morphogenesis.
    • Microscopy imaging enables assessment of spatial diffusion gradients in vitro and in vivo.
    • Quantitative analysis of diffusion mechanisms is challenged by measurement noise and sparse data, leading to parameter uncertainties.

    Purpose of the Study:

    • To develop a robust method for estimating parameters in diffusion models from image data.
    • To address challenges posed by noise and sparse observations in quantitative biological analysis.
    • To introduce a novel approach for assessing parameter uncertainty and identifiability in diffusion processes.

    Main Methods:

    • Developed a likelihood function for image-based measurements with log-normal noise.
    • Formulated a maximum likelihood estimation problem solved via PDE-constrained optimization.
    • Introduced profile likelihoods for assessing parameter uncertainty and practical identifiability.

    Main Results:

    • Successfully modeled dendritic cell guidance towards lymphatic vessels (haptotaxis) as a proof of concept.
    • Estimated five kinetic parameters of the haptotaxis model using artificial measurement data.
    • Demonstrated that profile likelihoods provide more rigorous uncertainty bounds compared to local approximation methods.

    Conclusions:

    • The novel approach for parameter estimation and identifiability analysis is broadly applicable to diffusion processes.
    • The profile likelihood method enhances the rigor of uncertainty bounds in diffusion modeling.
    • This work advances quantitative analysis of biological mechanisms driven by diffusion.