Drugs Resistance Analysis from Scarce Health Records via Multi-task Graph Representation

Clinicians prescribe antibiotics by looking at the patient's health record with an experienced eye. However, the therapy might be rendered futile if the patient has drug resistance. Determining drug resistance requires time-consuming laboratory-level testing while applying clinicians' heuristics in an automated way is difficult due to the categorical or binary medical events that constitute health records. In this paper, we propose a novel framework for rapid clinical intervention by viewing health records as graphs whose nodes are mapped from medical events and edges as correspondence between events in given a time window. A novel graph-based model is then proposed to extract informative features and yield automated drug resistance analysis from those high-dimensional and scarce graphs. The proposed method integrates multi-task learning into a common feature extracting graph encoder for simultaneous analyses of multiple drugs as well as stabilizing learning. On a massive dataset comprising over 110,000 patients with urinary tract infections, we verify the proposed method is capable of attaining superior performance on the drug resistance prediction problem. Furthermore, automated drug recommendations resemblant to laboratory-level testing can also be made based on the model resistance analysis.

Generalized Munchausen Reinforcement Learning using Tsallis KL Divergence

Many policy optimization approaches in reinforcement learning incorporate a Kullback-Leilbler (KL) divergence to the previous policy, to prevent the policy from changing too quickly. This idea was initially proposed in a seminal paper on Conservative Policy Iteration, with approximations given by algorithms like TRPO and Munchausen Value Iteration (MVI). We continue this line of work by investigating a generalized KL divergence -- called the Tsallis KL divergence -- which use the $q$-logarithm in the definition. The approach is a strict generalization, as $q = 1$ corresponds to the standard KL divergence; $q > 1$ provides a range of new options. We characterize the types of policies learned under the Tsallis KL, and motivate when $q >1$ could be beneficial. To obtain a practical algorithm that incorporates Tsallis KL regularization, we extend MVI, which is one of the simplest approaches to incorporate KL regularization. We show that this generalized MVI($q$) obtains significant improvements over the standard MVI($q = 1$) across 35 Atari games.

Cyclic Policy Distillation: Sample-Efficient Sim-to-Real Reinforcement Learning with Domain Randomization

Deep reinforcement learning with domain randomization learns a control policy in various simulations with randomized physical and sensor model parameters to become transferable to the real world in a zero-shot setting. However, a huge number of samples are often required to learn an effective policy when the range of randomized parameters is extensive due to the instability of policy updates. To alleviate this problem, we propose a sample-efficient method named Cyclic Policy Distillation (CPD). CPD divides the range of randomized parameters into several small sub-domains and assigns a local policy to each sub-domain. Then, the learning of local policies is performed while {\it cyclically} transitioning the target sub-domain to neighboring sub-domains and exploiting the learned values/policies of the neighbor sub-domains with a monotonic policy-improvement scheme. Finally, all of the learned local policies are distilled into a global policy for sim-to-real transfer. The effectiveness and sample efficiency of CPD are demonstrated through simulations with four tasks (Pendulum from OpenAIGym and Pusher, Swimmer, and HalfCheetah from Mujoco), and a real-robot ball-dispersal task.

Cancer Subtyping by Improved Transcriptomic Features Using Vector Quantized Variational Autoencoder

Defining and separating cancer subtypes is essential for facilitating personalized therapy modality and prognosis of patients. The definition of subtypes has been constantly recalibrated as a result of our deepened understanding. During this recalibration, researchers often rely on clustering of cancer data to provide an intuitive visual reference that could reveal the intrinsic characteristics of subtypes. The data being clustered are often omics data such as transcriptomics that have strong correlations to the underlying biological mechanism. However, while existing studies have shown promising results, they suffer from issues associated with omics data: sample scarcity and high dimensionality. As such, existing methods often impose unrealistic assumptions to extract useful features from the data while avoiding overfitting to spurious correlations. In this paper, we propose to leverage a recent strong generative model, Vector Quantized Variational AutoEncoder (VQ-VAE), to tackle the data issues and extract informative latent features that are crucial to the quality of subsequent clustering by retaining only information relevant to reconstructing the input. VQ-VAE does not impose strict assumptions and hence its latent features are better representations of the input, capable of yielding superior clustering performance with any mainstream clustering method. Extensive experiments and medical analysis on multiple datasets comprising 10 distinct cancers demonstrate the VQ-VAE clustering results can significantly and robustly improve prognosis over prevalent subtyping systems.

Automated Cancer Subtyping via Vector Quantization Mutual Information Maximization

Cancer subtyping is crucial for understanding the nature of tumors and providing suitable therapy. However, existing labelling methods are medically controversial, and have driven the process of subtyping away from teaching signals. Moreover, cancer genetic expression profiles are high-dimensional, scarce, and have complicated dependence, thereby posing a serious challenge to existing subtyping models for outputting sensible clustering. In this study, we propose a novel clustering method for exploiting genetic expression profiles and distinguishing subtypes in an unsupervised manner. The proposed method adaptively learns categorical correspondence from latent representations of expression profiles to the subtypes output by the model. By maximizing the problem -- agnostic mutual information between input expression profiles and output subtypes, our method can automatically decide a suitable number of subtypes. Through experiments, we demonstrate that our proposed method can refine existing controversial labels, and, by further medical analysis, this refinement is proven to have a high correlation with cancer survival rates.

$q$-Munchausen Reinforcement Learning

The recently successful Munchausen Reinforcement Learning (M-RL) features implicit Kullback-Leibler (KL) regularization by augmenting the reward function with logarithm of the current stochastic policy. Though significant improvement has been shown with the Boltzmann softmax policy, when the Tsallis sparsemax policy is considered, the augmentation leads to a flat learning curve for almost every problem considered. We show that it is due to the mismatch between the conventional logarithm and the non-logarithmic (generalized) nature of Tsallis entropy. Drawing inspiration from the Tsallis statistics literature, we propose to correct the mismatch of M-RL with the help of $q$-logarithm/exponential functions. The proposed formulation leads to implicit Tsallis KL regularization under the maximum Tsallis entropy framework. We show such formulation of M-RL again achieves superior performance on benchmark problems and sheds light on more general M-RL with various entropic indices $q$.

Enforcing KL Regularization in General Tsallis Entropy Reinforcement Learning via Advantage Learning

Maximum Tsallis entropy (MTE) framework in reinforcement learning has gained popularity recently by virtue of its flexible modeling choices including the widely used Shannon entropy and sparse entropy. However, non-Shannon entropies suffer from approximation error and subsequent underperformance either due to its sensitivity or the lack of closed-form policy expression. To improve the tradeoff between flexibility and empirical performance, we propose to strengthen their error-robustness by enforcing implicit Kullback-Leibler (KL) regularization in MTE motivated by Munchausen DQN (MDQN). We do so by drawing connection between MDQN and advantage learning, by which MDQN is shown to fail on generalizing to the MTE framework. The proposed method Tsallis Advantage Learning (TAL) is verified on extensive experiments to not only significantly improve upon Tsallis-DQN for various non-closed-form Tsallis entropies, but also exhibits comparable performance to state-of-the-art maximum Shannon entropy algorithms.

Multi-Tier Platform for Cognizing Massive Electroencephalogram

An end-to-end platform assembling multiple tiers is built for precisely cognizing brain activities. Being fed massive electroencephalogram (EEG) data, the time-frequency spectrograms are conventionally projected into the episode-wise feature matrices (seen as tier-1). A spiking neural network (SNN) based tier is designed to distill the principle information in terms of spike-streams from the rare features, which maintains the temporal implication in the nature of EEGs. The proposed tier-3 transposes time- and space-domain of spike patterns from the SNN; and feeds the transposed pattern-matrices into an artificial neural network (ANN, Transformer specifically) known as tier-4, where a special spanning topology is proposed to match the two-dimensional input form. In this manner, cognition such as classification is conducted with high accuracy. For proof-of-concept, the sleep stage scoring problem is demonstrated by introducing multiple EEG datasets with the largest comprising 42,560 hours recorded from 5,793 subjects. From experiment results, our platform achieves the general cognition overall accuracy of 87% by leveraging sole EEG, which is 2% superior to the state-of-the-art. Moreover, our developed multi-tier methodology offers visible and graphical interpretations of the temporal characteristics of EEG by identifying the critical episodes, which is demanded in neurodynamics but hardly appears in conventional cognition scenarios.

Cancer Subtyping via Embedded Unsupervised Learning on Transcriptomics Data

Cancer is one of the deadliest diseases worldwide. Accurate diagnosis and classification of cancer subtypes are indispensable for effective clinical treatment. Promising results on automatic cancer subtyping systems have been published recently with the emergence of various deep learning methods. However, such automatic systems often overfit the data due to the high dimensionality and scarcity. In this paper, we propose to investigate automatic subtyping from an unsupervised learning perspective by directly constructing the underlying data distribution itself, hence sufficient data can be generated to alleviate the issue of overfitting. Specifically, we bypass the strong Gaussianity assumption that typically exists but fails in the unsupervised learning subtyping literature due to small-sized samples by vector quantization. Our proposed method better captures the latent space features and models the cancer subtype manifestation on a molecular basis, as demonstrated by the extensive experimental results.