Ulisses M. Braga-Neto

h-index38
2papers

2 Papers

MNMay 30, 2018
Sequential Experimental Design for Optimal Structural Intervention in Gene Regulatory Networks Based on the Mean Objective Cost of Uncertainty

Mahdi Imani, Roozbeh Dehghannasiri, Ulisses M. Braga-Neto et al.

Scientists are attempting to use models of ever increasing complexity, especially in medicine, where gene-based diseases such as cancer require better modeling of cell regulation. Complex models suffer from uncertainty and experiments are needed to reduce this uncertainty. Because experiments can be costly and time-consuming it is desirable to determine experiments providing the most useful information. If a sequence of experiments is to be performed, experimental design is needed to determine the order. A classical approach is to maximally reduce the overall uncertainty in the model, meaning maximal entropy reduction. A recently proposed method takes into account both model uncertainty and the translational objective, for instance, optimal structural intervention in gene regulatory networks, where the aim is to alter the regulatory logic to maximally reduce the long-run likelihood of being in a cancerous state. The mean objective cost of uncertainty (MOCU) quantifies uncertainty based on the degree to which model uncertainty affects the objective. Experimental design involves choosing the experiment that yields the greatest reduction in MOCU. This paper introduces finite-horizon dynamic programming for MOCU-based sequential experimental design and compares it to the greedy approach, which selects one experiment at a time without consideration of the full horizon of experiments. A salient aspect of the paper is that it demonstrates the advantage of MOCU-based design over the widely used entropy-based design for both greedy and dynamic-programming strategies and investigates the effect of model conditions on the comparative performances.

LGAug 22, 2025
A State-Space Approach to Nonstationary Discriminant Analysis

Shuilian Xie, Mahdi Imani, Edward R. Dougherty et al.

Classical discriminant analysis assumes identically distributed training data, yet in many applications observations are collected over time and the class-conditional distributions drift. This population drift renders stationary classifiers unreliable. We propose a principled, model-based framework that embeds discriminant analysis within state-space models to obtain nonstationary linear discriminant analysis (NSLDA) and nonstationary quadratic discriminant analysis (NSQDA). For linear-Gaussian dynamics, we adapt Kalman smoothing to handle multiple samples per time step and develop two practical extensions: (i) an expectation-maximization (EM) approach that jointly estimates unknown system parameters, and (ii) a Gaussian mixture model (GMM)-Kalman method that simultaneously recovers unobserved time labels and parameters, a scenario common in practice. To address nonlinear or non-Gaussian drift, we employ particle smoothing to estimate time-varying class centroids, yielding fully nonstationary discriminant rules. Extensive simulations demonstrate consistent improvements over stationary linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and support vector machine (SVM) baselines, with robustness to noise, missing data, and class imbalance. This paper establishes a unified and data-efficient foundation for discriminant analysis under temporal distribution shift.