Optimizing Combinatory Drugs using Markov Chain-Based Models

Background: Combinatory drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatory drugs because the number of drug combinations increases exponentially with the types of drugs. Results: In this study, a searching method based on Markov chain is presented to optimize the combinatory drug concentrations. Its performance is compared with four stochastic optimization algorithms as benchmark methods by simulation and biological experiements. Both simulation results and experimental data demonstrate that the Markov Chain-based approach is more reliable and efficient than the benchmark algorithms.Conclusion: This article provides a versatile method for combinatory drug screening, which is of great significance for clinical drug combination therapy.

On hybridization of stochastic global optimization algorithms taking into account the features of their architecture

The work is devoted to the hybridization of stochastic global optimization algorithms depending on their architecture. The main methods of hybridization of stochastic optimization algorithms are listed. An example of hybridization of the algorithm is given, the modification of which became possible due to taking into account the characteristic architecture of the M-PCA algorithm.

PolyFold: An interactive visual simulator for distance-based protein folding

Recent advances in distance-based protein folding have led to a paradigm shift in protein structure prediction. Through sufficiently precise estimation of the inter-residue distance matrix for a protein sequence, it is now feasible to predict the correct folds for new proteins much more accurately than ever before. Despite the exciting progress, a dedicated visualization system that can dynamically capture the distance-based folding process is still lacking. Most molecular visualizers typically provide only a static view of a folded protein conformation, but do not capture the folding process. Even among the selected few graphical interfaces that do adopt a dynamic perspective, none of them are distance-based. Here we present PolyFold, an interactive visual simulator for dynamically capturing the distance-based protein folding process through real-time rendering of a distance matrix and its compatible spatial conformation as it folds in an intuitive and easy-to-use interface. PolyFold integrates highly convergent stochastic optimization algorithms with on-demand customizations and interactive manipulations to maximally satisfy the geometric constraints imposed by a distance matrix. PolyFold is capable of simulating the complex process of protein folding even on modest personal computers, thus making it accessible to the general public for fostering citizen science. Open source code of PolyFold is freely available for download at https://github.com/Bhattacharya-Lab/PolyFold. It is implemented in cross-platform Java and binary executables are available for macOS, Linux, and Windows.

Stochastic Optimization Methods for Parametric Level Set Reconstructions in 2D through-the-Wall Radar Imaging

In this paper, a comparison of stochastic optimization algorithms is presented for the reconstruction of electromagnetic profiles in through-the-wall radar imaging. We combine those stochastic optimization approaches with a shape-based representation of unknown targets which is based on a parametrized level set formulation. This way, we obtain a stochastic version of shape evolution with the goal of minimizing a given cost functional. As basis functions, we consider in particular Gaussian and Wendland radial basis functions. For the optimization task, we consider three variants of stochastic approaches, namely stochastic gradient descent, the Adam method as well as a more involved stochastic quasi-Newton scheme. A specific backtracking line search method is also introduced for this specific application of stochastic shape evolution. The physical scenery considered here is set in 2D assuming TM waves for simplicity. The goal is to localize and characterize (and eventually track) targets of interest hidden behind walls by solving the corresponding electromagnetic inverse problem. The results provide a good indication on the expected performance of similar schemes in a more realistic 3D setup.