Braden Soper

Haonan Zhu, Mary Silva, Jose Cadena et al.

Recent technological advances have introduced new high-throughput methods for studying host-virus interactions, but testing synergistic interactions between host gene pairs during infection remains relatively slow and labor intensive. Identification of multiple gene knockdowns that effectively inhibit viral replication requires a search over the combinatorial space of all possible target gene pairs and is infeasible via brute-force experiments. Although active learning methods for sequential experimental design have shown promise, existing approaches have generally been restricted to single-gene knockdowns or small-scale double knockdown datasets. In this study, we present an integrated Deep Active Learning (DeepAL) framework that incorporates information from a biological knowledge graph (SPOKE, the Scalable Precision Medicine Open Knowledge Engine) to efficiently search the configuration space of a large dataset of all pairwise knockdowns of 356 human genes in HIV infection. Through graph representation learning, the framework is able to generate task-specific representations of genes while also balancing the exploration-exploitation trade-off to pinpoint highly effective double-knockdown pairs. We additionally present an ensemble method for uncertainty quantification and an interpretation of the gene pairs selected by our algorithm via pathway analysis. To our knowledge, this is the first work to show promising results on double-gene knockdown experimental data of appreciable scale (356 by 356 matrix).

William A. Dawson, Ruben Glatt, Edward Rusu et al.

Information theoretic sensor management approaches are an ideal solution to state estimation problems when considering the optimal control of multi-agent systems, however they are too computationally intensive for large state spaces, especially when considering the limited computational resources typical of large-scale distributed multi-agent systems. Reinforcement learning (RL) is a promising alternative which can find approximate solutions to distributed optimal control problems that take into account the resource constraints inherent in many systems of distributed agents. However, the RL training can be prohibitively inefficient, especially in low-information environments where agents receive little to no feedback in large portions of the state space. We propose a hybrid information-driven multi-agent reinforcement learning (MARL) approach that utilizes information theoretic models as heuristics to help the agents navigate large sparse state spaces, coupled with information based rewards in an RL framework to learn higher-level policies. This paper presents our ongoing work towards this objective. Our preliminary findings show that such an approach can result in a system of agents that are approximately three orders of magnitude more efficient at exploring a sparse state space than naive baseline metrics. While the work is still in its early stages, it provides a promising direction for future research.

Rui Meng, Braden Soper, Herbert Lee et al.

We propose multivariate nonstationary Gaussian processes for jointly modeling multiple clinical variables, where the key parameters, length-scales, standard deviations and the correlations between the observed output, are all time dependent. We perform posterior inference via Hamiltonian Monte Carlo (HMC). We also provide methods for obtaining computationally efficient gradient-based maximum a posteriori (MAP) estimates. We validate our model on synthetic data as well as on electronic health records (EHR) data from Kaiser Permanente (KP). We show that the proposed model provides better predictive performance over a stationary model as well as uncovers interesting latent correlation processes across vitals which are potentially predictive of patient risk.

Rui Meng, Herbert Lee, Soper Braden et al.

Gaussian processes are a flexible Bayesian nonparametric modelling approach that has been widely applied but poses computational challenges. To address the poor scaling of exact inference methods, approximation methods based on sparse Gaussian processes (SGP) are attractive. An issue faced by SGP, especially in latent variable models, is the inefficient learning of the inducing inputs, which leads to poor model prediction. We propose a regularization approach by balancing the reconstruction performance of data and the approximation performance of the model itself. This regularization improves both inference and prediction performance. We extend this regularization approach into latent variable models with SGPs and show that performing variational inference (VI) on those models is equivalent to performing VI on a related empirical Bayes model.