Qingping Zhou (周清平)

Electrical Impedance Tomography (EIT) is widely applied in medical diagnosis, industrial inspection, and environmental monitoring. Combining the physical principles of the imaging system with the advantages of data-driven deep learning networks, physics-embedded deep unrolling networks have recently emerged as a promising solution in computational imaging. However, the inherent nonlinear and ill-posed properties of EIT image reconstruction still present challenges to existing methods in terms of accuracy and stability. To tackle this challenge, we propose the learned half-quadratic splitting (HQSNet) algorithm for incorporating physics into learning-based EIT imaging. We then apply Anderson acceleration (AA) to the HQSNet algorithm, denoted as AA-HQSNet, which can be interpreted as AA applied to the Gauss-Newton step and the learned proximal gradient descent step of the HQSNet, respectively. AA is a widely-used technique for accelerating the convergence of fixed-point iterative algorithms and has gained significant interest in numerical optimization and machine learning. However, the technique has received little attention in the inverse problems community thus far. Employing AA enhances the convergence rate compared to the standard HQSNet while simultaneously avoiding artifacts in the reconstructions. Lastly, we conduct rigorous numerical and visual experiments to show that the AA module strengthens the HQSNet, leading to robust, accurate, and considerably superior reconstructions compared to state-of-the-art methods. Our Anderson acceleration scheme to enhance HQSNet is generic and can be applied to improve the performance of various physics-embedded deep learning methods.

Cytochrome P450 3A4 (CYP3A4), a prominent member of the P450 enzyme superfamily, plays a crucial role in metabolizing various xenobiotics, including over 50% of clinically significant drugs. Evaluating CYP3A4 inhibition before drug approval is essential to avoiding potentially harmful pharmacokinetic drug−drug interactions (DDIs) and adverse drug reactions (ADRs). Despite the development of several CYP inhibitor prediction models, the primary approach for screening CYP inhibitors still relies on experimental methods. This might stem from the limitations of existing models, which only provide deterministic classification outcomes instead of precise inhibition intensity (e.g., IC50) and often suffer from inadequate prediction reliability. To address this challenge, we propose an uncertaintyguided regression model to accurately predict the IC50 values of anti-CYP3A4 activities. First, a comprehensive data set of CYP3A4 inhibitors was compiled, consisting of 27,045 compounds with classification labels, including 4395 compounds with explicit IC50 values. Second, by integrating the predictions of the classification model trained on a larger data set and introducing an evidential uncertainty method to rank prediction confidence, we obtained a high-precision and reliable regression model. Finally, we use the evidential uncertainty values as a trustworthy indicator to perform a virtual screening of an in-house compound set. The in vitro experiment results revealed that this new indicator significantly improved the hit ratio and reduced false positives among the topranked compounds. Specifically, among the top 20 compounds ranked with uncertainty, 15 compounds were identified as novel CYP3A4 inhibitors, and three of them exhibited activities less than 1 μM. In summary, our findings highlight the effectiveness of incorporating uncertainty in compound screening, providing a promising strategy for drug discovery and development.

We provide a complete framework for performing infinite dimensional Bayesian inference and uncertainty quantification for image reconstruction with Poisson data. In particular, we address the following issues to make the Bayesian framework applicable in practice. We first introduce a positivity-preserving reparametrization, and we prove that under the reparametrization and a hybrid prior, the posterior distribution is well-posed in the infinite dimensional setting. Second, we provide a dimension-independent Markov chain Monte Carlo algorithm, based on the preconditioned Crank–Nicolson Langevin method, in which we use a primal-dual scheme to compute the offset direction. Third, we give a method combining the model discrepancy method and maximum likelihood estimation to determine the regularization parameter in the hybrid prior. Finally we propose to use the obtained posterior distribution to detect artifacts in a recovered image. We provide an example to demonstrate the effectiveness of the proposed method.