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).

In the dynamic hospital setting, decision support can be a valuable tool for improving patient outcomes. Data-driven inference of future outcomes is challenging in this dynamic setting, where long sequences such as laboratory tests and medications are updated frequently. This is due in part to heterogeneity of data types and mixed-sequence types contained in variable length sequences. In this work we design a probabilistic unsupervised model for multiple arbitrary-length sequences contained in hospitalization Electronic Health Record (EHR) data. The model uses a latent variable structure and captures complex relationships between medications, diagnoses, laboratory tests, neurological assessments, and medications. It can be trained on original data, without requiring any lossy transformations or time binning. Inference algorithms are derived that use partial data to infer properties of the complete sequences, including their length and presence of specific values. We train this model on data from subjects receiving medical care in the Kaiser Permanente Northern California integrated healthcare delivery system. The results are evaluated against held-out data for predicting the length of sequences and presence of Intensive Care Unit (ICU) in hospitalization bed sequences. Our method outperforms a baseline approach, showing that in these experiments the trained model captures information in the sequences that is informative of their future values.

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.

Many machine learning problems can be formulated as consensus optimization problems which can be solved efficiently via a cooperative multi-agent system. However, the agents in the system can be unreliable due to a variety of reasons: noise, faults and attacks. Thus, providing falsified data leads the optimization process in a wrong direction, and degrades the performance of distributed machine learning algorithms. This paper considers the problem of decentralized learning using ADMM in the presence of unreliable agents. First, we rigorously analyze the effect of falsified updates (in ADMM learning iterations) on the convergence behavior of multi-agent system. We show that the algorithm linearly converges to a neighborhood of the optimal solution under certain conditions and characterize the neighborhood size analytically. Next, we provide guidelines for network structure design to achieve a faster convergence. We also provide necessary conditions on the falsified updates for exact convergence to the optimal solution. Finally, to mitigate the influence of unreliable agents, we propose a robust variant of ADMM and show its resilience to unreliable agents.

Characterizing a patient's progression through stages of sepsis is critical for enabling risk stratification and adaptive, personalized treatment. However, commonly used sepsis diagnostic criteria fail to account for significant underlying heterogeneity, both between patients as well as over time in a single patient. We introduce a hidden Markov model of sepsis progression that explicitly accounts for patient heterogeneity. Benchmarked against two sepsis diagnostic criteria, the model provides a useful tool to uncover a patient's latent sepsis trajectory and to identify high-risk patients in whom more aggressive therapy may be indicated.