Andrei Lixandru

Udesh Habaraduwa, Andrei Lixandru

The advancement of human healthspan and bioengineering relies heavily on predicting the behavior of complex biological systems. While high-throughput multiomics data is becoming increasingly abundant, converting this data into actionable predictive models remains a bottleneck. High-capacity, datadriven simulation systems are critical in this landscape; unlike classical mechanistic models restricted by prior knowledge, these architectures can infer latent interactions directly from observational data, allowing for the simulation of temporal trajectories and the anticipation of downstream intervention effects in personalized medicine and synthetic biology. To address this challenge, we introduce Neural Ordinary Differential Equations (NODEs) as a dynamic framework for learning the complex interplay between the proteome and metabolome. We applied this framework to time-series data derived from engineered Escherichia coli strains, modeling the continuous dynamics of metabolic pathways. The proposed NODE architecture demonstrates superior performance in capturing system dynamics compared to traditional machine learning pipelines. Our results show a greater than 90% improvement in root mean squared error over baselines across both Limonene (up to 94.38% improvement) and Isopentenol (up to 97.65% improvement) pathway datasets. Furthermore, the NODE models demonstrated a 1000x acceleration in inference time, establishing them as a scalable, high-fidelity tool for the next generation of metabolic engineering and biological discovery.

Andrei Lixandru

Proximal Policy Optimization with Adaptive Exploration (axPPO) is introduced as a novel learning algorithm. This paper investigates the exploration-exploitation tradeoff within the context of reinforcement learning and aims to contribute new insights into reinforcement learning algorithm design. The proposed adaptive exploration framework dynamically adjusts the exploration magnitude during training based on the recent performance of the agent. Our proposed method outperforms standard PPO algorithms in learning efficiency, particularly when significant exploratory behavior is needed at the beginning of the learning process.

Andrei Lixandru

This study examines the potential causal relationship between head injury and the risk of developing Alzheimer's disease (AD) using Bayesian networks and regression models. Using a dataset of 2,149 patients, we analyze key medical history variables, including head injury history, memory complaints, cardiovascular disease, and diabetes. Logistic regression results suggest an odds ratio of 0.88 for head injury, indicating a potential but statistically insignificant protective effect against AD. In contrast, memory complaints exhibit a strong association with AD, with an odds ratio of 4.59. Linear regression analysis further confirms the lack of statistical significance for head injury (coefficient: -0.0245, p = 0.469) while reinforcing the predictive importance of memory complaints. These findings highlight the complex interplay of medical history factors in AD risk assessment and underscore the need for further research utilizing larger datasets and advanced causal modeling techniques.

Andrei Lixandru, Marcel van Gerven, Sergio Pequito

Distributed optimization is fundamental to modern machine learning applications like federated learning, but existing methods often struggle with ill-conditioned problems and face stability-versus-speed tradeoffs. We introduce fractional order distributed optimization (FrODO); a theoretically-grounded framework that incorporates fractional-order memory terms to enhance convergence properties in challenging optimization landscapes. Our approach achieves provable linear convergence for any strongly connected network. Through empirical validation, our results suggest that FrODO achieves up to 4 times faster convergence versus baselines on ill-conditioned problems and 2-3 times speedup in federated neural network training, while maintaining stability and theoretical guarantees.