Traction force microscopy with optimized regularization and automated Bayesian parameter selection for comparing cells

Adherent cells exert traction forces on to their environment, which allows them to migrate, to maintain tissue integrity, and to form complex multicellular structures. This traction can be measured in a perturbation-free manner with traction force microscopy (TFM). In TFM, traction is usually calculated via the solution of a linear system, which is complicated by undersampled input data, acquisition noise, and large condition numbers for some methods. Therefore, standard TFM algorithms either employ data filtering or regularization. However, these approaches require a manual selection of filter- or regularization parameters and consequently exhibit a substantial degree of subjectiveness. This shortcoming is particularly serious when cells in different conditions are to be compared because optimal noise suppression needs to be adapted for every situation, which invariably results in systematic errors. Here, we systematically test the performance of new methods from computer vision and Bayesian inference for solving the inverse problem in TFM. We compare two classical schemes, L1- and L2-regularization, with three previously untested schemes, namely Elastic Net regularization, Proximal Gradient Lasso, and Proximal Gradient Elastic Net. Overall, we find that Elastic Net regularization, which combines L1 and L2 regularization, outperforms all other methods with regard to accuracy of traction reconstruction. Next, we develop two methods, Bayesian L2 regularization and Advanced Bayesian L2 regularization, for automatic, optimal L2 regularization. Using artificial data and experimental data, we show that these methods enable robust reconstruction of traction without requiring a difficult selection of regularization parameters specifically for each data set. Thus, Bayesian methods can mitigate the considerable uncertainty inherent in comparing cellular traction forces

First order algorithms in variational image processing

Variational methods in imaging are nowadays developing towards a quite universal and flexible tool, allowing for highly successful approaches on tasks like denoising, deblurring, inpainting, segmentation, super-resolution, disparity, and optical flow estimation. The overall structure of such approaches is of the form ${\cal D}(Ku) + \alpha {\cal R} (u) \rightarrow \min_u$ ; where the functional ${\cal D}$ is a data fidelity term also depending on some input data $f$ and measuring the deviation of $Ku$ from such and ${\cal R}$ is a regularization functional. Moreover $K$ is a (often linear) forward operator modeling the dependence of data on an underlying image, and $\alpha$ is a positive regularization parameter. While ${\cal D}$ is often smooth and (strictly) convex, the current practice almost exclusively uses nonsmooth regularization functionals. The majority of successful techniques is using nonsmooth and convex functionals like the total variation and generalizations thereof or $\ell_1$-norms of coefficients arising from scalar products with some frame system. The efficient solution of such variational problems in imaging demands for appropriate algorithms. Taking into account the specific structure as a sum of two very different terms to be minimized, splitting algorithms are a quite canonical choice. Consequently this field has revived the interest in techniques like operator splittings or augmented Lagrangians. Here we shall provide an overview of methods currently developed and recent results as well as some computational studies providing a comparison of different methods and also illustrating their success in applications.Comment: 60 pages, 33 figure

Online convex optimization meets sparsity

Tracking time-varying sparse signals is a recent problem with widespread applications. Techniques derived from compressed sensing, Lasso, and Kalman filtering have been proposed in the literature, which mainly present two drawbacks: the prior knowledge of specific evolution models and the lack of theoretical guarantees. In this work, we propose a new perspective on the problem, based on the theory on online convex optimization, which has been developed in the machine learning community. We exploit a strongly convex model, and we develop online algorithms, for which we are able to provide a dynamic regret analysis. A few simulations that support the theoretical results are finally presented

Social-sparsity brain decoders: faster spatial sparsity

Spatially-sparse predictors are good models for brain decoding: they give accurate predictions and their weight maps are interpretable as they focus on a small number of regions. However, the state of the art, based on total variation or graph-net, is computationally costly. Here we introduce sparsity in the local neighborhood of each voxel with social-sparsity, a structured shrinkage operator. We find that, on brain imaging classification problems, social-sparsity performs almost as well as total-variation models and better than graph-net, for a fraction of the computational cost. It also very clearly outlines predictive regions. We give details of the model and the algorithm.Comment: in Pattern Recognition in NeuroImaging, Jun 2016, Trento, Italy. 201