Understanding disease progression at the molecular pathway level usually requires capturing both structural dependencies between pathways and the temporal dynamics of disease evolution. In this work, we solve the former challenge by developing a biologically informed graph-forming method to efficiently construct pathway graphs for subjects from our newly curated JR5558 mouse transcriptomics dataset. We then develop Graph-level Pseudotime Analysis (GPA) to infer graph-level trajectories that reveal how disease progresses at the population level, rather than in individual subjects. Based on the trajectories estimated by GPA, we identify the most sensitive pathways that drive disease stage transitions. In addition, we measure changes in pathway features using neural stochastic differential equations (SDEs), which enables us to formally define and compute pathway stability and disease bifurcation points (points of no return), two fundamental problems in disease progression research. We further extend our theory to the case when pathways can interact with each other, enabling a more comprehensive and multi-faceted characterization of disease phenotypes. The comprehensive experimental results demonstrate the effectiveness of our framework in reconstructing the dynamics of the pathway, identifying critical transitions, and providing novel insights into the mechanistic understanding of disease evolution.

Optimization algorithms are very different from human optimizers. A human being would gain more experiences through problem-solving, which helps her/him in solving a new unseen problem. Yet an optimization algorithm never gains any experiences by solving more problems. In recent years, efforts have been made towards endowing optimization algorithms with some abilities of experience learning, which is regarded as experience-based optimization. In this paper, we argue that hard optimization problems could be tackled efficiently by making better use of experiences gained in related problems. We demonstrate our ideas in the context of expensive optimization, where we aim to find a near-optimal solution to an expensive optimization problem with as few fitness evaluations as possible. To achieve this, we propose an experience-based surrogate-assisted evolutionary algorithm (SAEA) framework to enhance the optimization efficiency of expensive problems, where experiences are gained across related expensive tasks via a novel meta-learning method. These experiences serve as the task-independent parameters of a deep kernel learning surrogate, then the solutions sampled from the target task are used to adapt task-specific parameters for the surrogate. With the help of experience learning, competitive regression-based surrogates can be initialized using only 1$d$ solutions from the target task ($d$ is the dimension of the decision space). Our experimental results on expensive multi-objective and constrained optimization problems demonstrate that experiences gained from related tasks are beneficial for the saving of evaluation budgets on the target problem.

Black-box artificial intelligence (AI) induction methods such as deep reinforcement learning (DRL) are increasingly being used to find optimal policies for a given control task. Although policies represented using a black-box AI are capable of efficiently executing the underlying control task and achieving optimal closed-loop performance -- controlling the agent from initial time step until the successful termination of an episode, the developed control rules are often complex and neither interpretable nor explainable. In this paper, we use a recently proposed nonlinear decision-tree (NLDT) approach to find a hierarchical set of control rules in an attempt to maximize the open-loop performance for approximating and explaining the pre-trained black-box DRL (oracle) agent using the labelled state-action dataset. Recent advances in nonlinear optimization approaches using evolutionary computation facilitates finding a hierarchical set of nonlinear control rules as a function of state variables using a computationally fast bilevel optimization procedure at each node of the proposed NLDT. Additionally, we propose a re-optimization procedure for enhancing closed-loop performance of an already derived NLDT. We evaluate our proposed methodologies on four different control problems having two to four discrete actions. In all these problems our proposed approach is able to find simple and interpretable rules involving one to four non-linear terms per rule, while simultaneously achieving on par closed-loop performance when compared to a trained black-box DRL agent. The obtained results are inspiring as they suggest the replacement of complicated black-box DRL policies involving thousands of parameters (making them non-interpretable) with simple interpretable policies. Results are encouraging and motivating to pursue further applications of proposed approach in solving more complex control tasks.