Hua Zheng

Wei Xie, Keqi Wang, Hua Zheng et al.

Driven by the critical needs of biomanufacturing 4.0, we introduce a probabilistic knowledge graph hybrid model characterizing the risk- and science-based understanding of bioprocess mechanisms. It can faithfully capture the important properties, including nonlinear reactions, partially observed state, and nonstationary dynamics. Given very limited real process observations, we derive a posterior distribution quantifying model estimation uncertainty. To avoid the evaluation of intractable likelihoods, Approximate Bayesian Computation sampling with Sequential Monte Carlo (ABC-SMC) is utilized to approximate the posterior distribution. Under high stochastic and model uncertainties, it is computationally expensive to match output trajectories. Therefore, we create a linear Gaussian dynamic Bayesian network (LG-DBN) auxiliary likelihood-based ABC-SMC approach. Through matching the summary statistics driven through LG-DBN likelihood that can capture critical interactions and variations, the proposed algorithm can accelerate hybrid model inference, support process monitoring, and facilitate mechanism learning and robust control.

Hua Zheng, Wei Xie

Built on our previous study on green simulation assisted policy gradient (GS-PG) focusing on trajectory-based reuse, in this paper, we consider infinite-horizon Markov Decision Processes and create a new importance sampling based policy gradient optimization approach to support dynamic decision making. The existing GS-PG method was designed to learn from complete episodes or process trajectories, which limits its applicability to low-data situations and flexible online process control. To overcome this limitation, the proposed approach can selectively reuse the most related partial trajectories, i.e., the reuse unit is based on per-step or per-decision historical observations. In specific, we create a mixture likelihood ratio (MLR) based policy gradient optimization that can leverage the information from historical state-action transitions generated under different behavioral policies. The proposed variance reduction experience replay (VRER) approach can intelligently select and reuse most relevant transition observations, improve the policy gradient estimation, and accelerate the learning of optimal policy. Our empirical study demonstrates that it can improve optimization convergence and enhance the performance of state-of-the-art policy optimization approaches such as actor-critic method and proximal policy optimizations.

Hua Zheng, Wei Xie, M. Ben Feng

For reinforcement learning on complex stochastic systems where many factors dynamically impact the output trajectories, it is desirable to effectively leverage the information from historical samples collected in previous iterations to accelerate policy optimization. Classical experience replay allows agents to remember by reusing historical observations. However, the uniform reuse strategy that treats all observations equally overlooks the relative importance of different samples. To overcome this limitation, we propose a general variance reduction based experience replay (VRER) framework that can selectively reuse the most relevant samples to improve policy gradient estimation. This selective mechanism can adaptively put more weight on past samples that are more likely to be generated by the current target distribution. Our theoretical and empirical studies show that the proposed VRER can accelerate the learning of optimal policy and enhance the performance of state-of-the-art policy optimization approaches.

Hua Zheng, Wei Xie, Ilya O. Ryzhov et al.

This paper presents a novel methodological framework, called the Actor-Simulator, that incorporates the calibration of digital twins into model-based reinforcement learning for more effective control of stochastic systems with complex nonlinear dynamics. Traditional model-based control often relies on restrictive structural assumptions (such as linear state transitions) and fails to account for parameter uncertainty in the model. These issues become particularly critical in industries such as biopharmaceutical manufacturing, where process dynamics are complex and not fully known, and only a limited amount of data is available. Our approach jointly calibrates the digital twin and searches for an optimal control policy, thus accounting for and reducing model error. We balance exploration and exploitation by using policy performance as a guide for data collection. This dual-component approach provably converges to the optimal policy, and outperforms existing methods in extensive numerical experiments based on the biopharmaceutical manufacturing domain.

Hua Zheng, Wei Xie, Keqi Wang et al.

Driven by the key challenges of cell therapy manufacturing, including high complexity, high uncertainty, and very limited process observations, we propose a hybrid model-based reinforcement learning (RL) to efficiently guide process control. We first create a probabilistic knowledge graph (KG) hybrid model characterizing the risk- and science-based understanding of biomanufacturing process mechanisms and quantifying inherent stochasticity, e.g., batch-to-batch variation. It can capture the key features, including nonlinear reactions, nonstationary dynamics, and partially observed state. This hybrid model can leverage existing mechanistic models and facilitate learning from heterogeneous process data. A computational sampling approach is used to generate posterior samples quantifying model uncertainty. Then, we introduce hybrid model-based Bayesian RL, accounting for both inherent stochasticity and model uncertainty, to guide optimal, robust, and interpretable dynamic decision making. Cell therapy manufacturing examples are used to empirically demonstrate that the proposed framework can outperform the classical deterministic mechanistic model assisted process optimization.

Qing Lyu, Hua Zheng, Daoxin Li et al.

Recursive noun phrases (NPs) have interesting semantic properties. For example, "my favorite new movie" is not necessarily my favorite movie, whereas "my new favorite movie" is. This is common sense to humans, yet it is unknown whether language models have such knowledge. We introduce the Recursive Noun Phrase Challenge (RNPC), a dataset of three textual inference tasks involving textual entailment and event plausibility comparison, precisely targeting the understanding of recursive NPs. When evaluated on RNPC, state-of-the-art Transformer models only perform around chance. Still, we show that such knowledge is learnable with appropriate data. We further probe the models for relevant linguistic features that can be learned from our tasks, including modifier semantic category and modifier scope. Finally, models trained on RNPC achieve strong zero-shot performance on an extrinsic Harm Detection evaluation task, showing the usefulness of the understanding of recursive NPs in downstream applications.

Hua Zheng, Wei Xie, M. Ben Feng

Experience replay is a core ingredient of modern deep reinforcement learning, yet its benefits in policy optimization are poorly understood beyond empirical heuristics. This paper develops a novel theoretical framework for experience replay in modern policy gradient methods, where two sources of dependence fundamentally complicate analysis: Markovian correlations along trajectories and policy drift across optimization iterations. We introduce a new proof technique based on auxiliary Markov chains and lag-based decoupling that makes these dependencies tractable. Within this framework, we derive finite-time bias bounds for policy-gradient estimators under replay, identifying how bias scales with the cumulative policy update, the mixing time of the underlying dynamics, and the age of buffered data, thereby formalizing the practitioner's rule of avoiding overly stale replay. We further provide a correlation-aware variance decomposition showing how sample dependence governs gradient variance from replay and when replay is beneficial. Building on these characterizations, we establish the finite-time convergence guarantees for experience-replay-based policy optimization, explicitly quantifying how buffer size, sample correlation, and mixing jointly determine the convergence rate and revealing an inherent bias-variance trade-off: larger buffers can reduce variance by averaging less correlated samples but can increase bias as data become stale. These results offer a principled guide for buffer sizing and replay schedules, bridging prior empirical findings with quantitative theory.

Hua Zheng, Wei Xie, Ilya O. Ryzhov et al.

Biopharmaceutical manufacturing is a rapidly growing industry with impact in virtually all branches of medicines. Biomanufacturing processes require close monitoring and control, in the presence of complex bioprocess dynamics with many interdependent factors, as well as extremely limited data due to the high cost of experiments as well as the novelty of personalized bio-drugs. We develop a novel model-based reinforcement learning framework that can achieve human-level control in low-data environments. The model uses a dynamic Bayesian network to capture causal interdependencies between factors and predict how the effects of different inputs propagate through the pathways of the bioprocess mechanisms. This enables the design of process control policies that are both interpretable and robust against model risk. We present a computationally efficient, provably convergence stochastic gradient method for optimizing such policies. Validation is conducted on a realistic application with a multi-dimensional, continuous state variable.

Damai Dai, Hua Zheng, Zhifang Sui et al.

Conventional Machine Reading Comprehension (MRC) has been well-addressed by pattern matching, but the ability of commonsense reasoning remains a gap between humans and machines. Previous methods tackle this problem by enriching word representations via pre-trained Knowledge Graph Embeddings (KGE). However, they make limited use of a large number of connections between nodes in Knowledge Graphs (KG), which could be pivotal cues to build the commonsense reasoning chains. In this paper, we propose a Plug-and-play module to IncorporatE Connection information for commonsEnse Reasoning (PIECER). Beyond enriching word representations with knowledge embeddings, PIECER constructs a joint query-passage graph to explicitly guide commonsense reasoning by the knowledge-oriented connections between words. Further, PIECER has high generalizability since it can be plugged into suitable positions in any MRC model. Experimental results on ReCoRD, a large-scale public MRC dataset requiring commonsense reasoning, show that PIECER introduces stable performance improvements for four representative base MRC models, especially in low-resource settings.

Hua Zheng, Ilya O. Ryzhov, Wei Xie et al.

Comorbid chronic conditions are common among people with type 2 diabetes. We developed an Artificial Intelligence algorithm, based on Reinforcement Learning (RL), for personalized diabetes and multi-morbidity management with strong potential to improve health outcomes relative to current clinical practice. In this paper, we modeled glycemia, blood pressure and cardiovascular disease (CVD) risk as health outcomes using a retrospective cohort of 16,665 patients with type 2 diabetes from New York University Langone Health ambulatory care electronic health records in 2009 to 2017. We trained a RL prescription algorithm that recommends a treatment regimen optimizing patients' cumulative health outcomes using their individual characteristics and medical history at each encounter. The RL recommendations were evaluated on an independent subset of patients. The results demonstrate that the proposed personalized reinforcement learning prescriptive framework for type 2 diabetes yielded high concordance with clinicians' prescriptions and substantial improvements in glycemia, blood pressure, cardiovascular disease risk outcomes.

Damai Dai, Hua Zheng, Fuli Luo et al.

Conventional Knowledge Graph Completion (KGC) assumes that all test entities appear during training. However, in real-world scenarios, Knowledge Graphs (KG) evolve fast with out-of-knowledge-graph (OOKG) entities added frequently, and we need to represent these entities efficiently. Most existing Knowledge Graph Embedding (KGE) methods cannot represent OOKG entities without costly retraining on the whole KG. To enhance efficiency, we propose a simple and effective method that inductively represents OOKG entities by their optimal estimation under translational assumptions. Given pretrained embeddings of the in-knowledge-graph (IKG) entities, our method needs no additional learning. Experimental results show that our method outperforms the state-of-the-art methods with higher efficiency on two KGC tasks with OOKG entities.

Hua Zheng, Wei Xie, Mingbin Ben Feng

Biopharmaceutical manufacturing faces critical challenges, including complexity, high variability, lengthy lead time, and limited historical data and knowledge of the underlying system stochastic process. To address these challenges, we propose a green simulation assisted model-based reinforcement learning to support process online learning and guide dynamic decision making. Basically, the process model risk is quantified by the posterior distribution. At any given policy, we predict the expected system response with prediction risk accounting for both inherent stochastic uncertainty and model risk. Then, we propose green simulation assisted reinforcement learning and derive the mixture proposal distribution of decision process and likelihood ratio based metamodel for the policy gradient, which can selectively reuse process trajectory outputs collected from previous experiments to increase the simulation data-efficiency, improve the policy gradient estimation accuracy, and speed up the search for the optimal policy. Our numerical study indicates that the proposed approach demonstrates the promising performance.

Wei Xie, Yuan Yi, Hua Zheng

To integrate strategic, tactical and operational decisions, the two-stage optimization has been widely used to guide dynamic decision making. In this paper, we study the two-stage stochastic programming for complex systems with unknown response estimated by simulation. We introduce the global-local metamodel assisted two-stage optimization via simulation that can efficiently employ the simulation resource to iteratively solve for the optimal first- and second-stage decisions. Specifically, at each visited first-stage decision, we develop a local metamodel to simultaneously solve a set of scenario-based second-stage optimization problems, which also allows us to estimate the optimality gap. Then, we construct a global metamodel accounting for the errors induced by: (1) using a finite number of scenarios to approximate the expected future cost occurring in the planning horizon, (2) second-stage optimality gap, and (3) finite visited first-stage decisions. Assisted by the global-local metamodel, we propose a new simulation optimization approach that can efficiently and iteratively search for the optimal first- and second-stage decisions. Our framework can guarantee the convergence of optimal solution for the discrete two-stage optimization with unknown objective, and the empirical study indicates that it achieves substantial efficiency and accuracy.