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Motivated by the challenges in analyzing gut microbiome and metagenomic data, this work aims to tackle the issue of measurement errors in high-dimensional regression models that involve compositional covariates. This paper marks a pioneering effort in conducting statistical inference on high-dimensional compositional data affected by mismeasured or contaminated data. We introduce a calibration approach tailored for the linear log-contrast model. Under relatively lenient conditions regarding the sparsity level of the parameter, we have established the asymptotic normality of the estimator for inference. Numerical experiments and an application in microbiome study have demonstrated the efficacy of our high-dimensional calibration strategy in minimizing bias and achieving the expected coverage rates for confidence intervals. Moreover, the potential application of our proposed methodology extends well beyond compositional data, suggesting its adaptability for a wide range of research contexts.

Utilizing natural history data as external control plays an important role in the clinical development of rare diseases, since placebo groups in double-blind randomization trials may not be available due to ethical reasons and low disease prevalence. This article proposed an innovative approach for utilizing natural history data to support rare disease clinical development by constructing reference centile charts. Due to the deterioration nature of certain rare diseases, the distributions of clinical endpoints can be age-dependent and have an absorbing state of zero, which can result in censored natural history data. Existing methods of reference centile charts can not be directly used in the censored natural history data. Therefore, we propose a new calibrated zero-inflated kernel quantile (ZIKQ) estimation to construct reference centile charts from censored natural history data. Using the application to Duchenne Muscular Dystrophy drug development, we demonstrate that the reference centile charts using the ZIKQ method can be implemented to evaluate treatment efficacy and facilitate a more targeted patient enrollment in rare disease clinical development.

Reinforcement Learning (RL) has made promising progress in planning and decision-making for Autonomous Vehicles (AVs) in simple driving scenarios. However, existing RL algorithms for AVs fail to learn critical driving skills in complex urban scenarios. First, urban driving scenarios require AVs to handle multiple driving tasks of which conventional RL algorithms are incapable. Second, the presence of other vehicles in urban scenarios results in a dynamically changing environment, which challenges RL algorithms to plan the action and trajectory of the AV. In this work, we propose an action and trajectory planner using Hierarchical Reinforcement Learning (atHRL) method, which models the agent behavior in a hierarchical model by using the perception of the lidar and birdeye view. The proposed atHRL method learns to make decisions about the agent's future trajectory and computes target waypoints under continuous settings based on a hierarchical DDPG algorithm. The waypoints planned by the atHRL model are then sent to a low-level controller to generate the steering and throttle commands required for the vehicle maneuver. We empirically verify the efficacy of atHRL through extensive experiments in complex urban driving scenarios that compose multiple tasks with the presence of other vehicles in the CARLA simulator. The experimental results suggest a significant performance improvement compared to the state-of-the-art RL methods., Comment: ICML Workshop on New Frontiers in Learning, Control, and Dynamical Systems

Transcriptome-wide association studies (TWAS) are powerful tools for identifying putative causal genes by integrating genome-wide association studies and gene expression data. However, most TWAS methods focus on linear associations between genes and traits, ignoring the complex nonlinear relationships that exist in biological systems. To address this limitation, we propose a novel quantile transcriptomics framework, QTWAS, that takes into account the nonlinear and heterogeneous nature of gene-trait associations. Our approach integrates a quantile-based gene expression model into the TWAS model, which allows for the discovery of nonlinear and heterogeneous gene-trait associations. By conducting comprehensive simulations and examining various psychiatric and neurodegenerative traits, we demonstrate that the proposed model outperforms traditional techniques in identifying gene-trait associations. Additionally, QTWAS can uncover important insights into nonlinear relationships between gene expression levels and phenotypes, complementing traditional TWAS approaches. We further show applications to 100 continuous traits from the UK Biobank and 10 binary traits related to brain disorders.

In microbiome studies, it is of interest to use a sample from a population of microbes, such as the gut microbiota community, to estimate the population proportion of these taxa. However, due to biases introduced in sampling and preprocessing steps, these observed taxa abundances may not reflect true taxa abundance patterns in the ecosystem. Repeated measures, including longitudinal study designs, may be potential solutions to mitigate the discrepancy between observed abundances and true underlying abundances. Yet, widely observed zero-inflation and over-dispersion issues can distort downstream statistical analyses aiming to associate taxa abundances with covariates of interest. To this end, we propose a Zero-Inflated Poisson Gamma (ZIPG) framework to address the aforementioned challenges. From a perspective of measurement errors, we accommodate the discrepancy between observations and truths by decomposing the mean parameter in Poisson regression into a true abundance level and a multiplicative measurement of sampling variability from the microbial ecosystem. Then, we provide a flexible model by connecting both mean abundance and the variability to different covariates, and build valid statistical inference procedures for both parameter estimation and hypothesis testing. Through comprehensive simulation studies and real data applications, the proposed ZIPG method provides significant insights into distinguished differential variability and abundance.

We present an end-to-end Reinforcement Learning(RL) framework for robotic manipulation tasks, using a robust and efficient keypoints representation. The proposed method learns keypoints from camera images as the state representation, through a self-supervised autoencoder architecture. The keypoints encode the geometric information, as well as the relationship of the tool and target in a compact representation to ensure efficient and robust learning. After keypoints learning, the RL step then learns the robot motion from the extracted keypoints state representation. The keypoints and RL learning processes are entirely done in the simulated environment. We demonstrate the effectiveness of the proposed method on robotic manipulation tasks including grasping and pushing, in different scenarios. We also investigate the generalization capability of the trained model. In addition to the robust keypoints representation, we further apply domain randomization and adversarial training examples to achieve zero-shot sim-to-real transfer in real-world robotic manipulation tasks., Comment: 8 pages

Ensemble learning consistently improves the performance of multi-class classification through aggregating a series of base classifiers. To this end, data-independent ensemble methods like Error Correcting Output Codes (ECOC) attract increasing attention due to its easiness of implementation and parallelization. Specifically, traditional ECOCs and its general extension N-ary ECOC decompose the original multi-class classification problem into a series of independent simpler classification subproblems. Unfortunately, integrating ECOCs, especially N-ary ECOC with deep neural networks, termed as deep N-ary ECOC, is not straightforward and yet fully exploited in the literature, due to the high expense of training base learners. To facilitate the training of N-ary ECOC with deep learning base learners, we further propose three different variants of parameter sharing architectures for deep N-ary ECOC. To verify the generalization ability of deep N-ary ECOC, we conduct experiments by varying the backbone with different deep neural network architectures for both image and text classification tasks. Furthermore, extensive ablation studies on deep N-ary ECOC show its superior performance over other deep data-independent ensemble methods., Comment: EAI MOBIMEDIA 2020

Learning-based methods have been used to pro-gram robotic tasks in recent years. However, extensive training is usually required not only for the initial task learning but also for generalizing the learned model to the same task but in different environments. In this paper, we propose a novel Deep Reinforcement Learning algorithm for efficient task generalization and environment adaptation in the robotic task learning problem. The proposed method is able to efficiently generalize the previously learned task by model fusion to solve the environment adaptation problem. The proposed Deep Model Fusion (DMF) method reuses and combines the previously trained model to improve the learning efficiency and results.Besides, we also introduce a Multi-objective Guided Reward(MGR) shaping technique to further improve training efficiency.The proposed method was benchmarked with previous methods in various environments to validate its effectiveness., Comment: Accepted by ROBIO 2019

Robotic drawing has become increasingly popular as an entertainment and interactive tool. In this paper we present RoboCoDraw, a real-time collaborative robot-based drawing system that draws stylized human face sketches interactively in front of human users, by using the Generative Adversarial Network (GAN)-based style transfer and a Random-Key Genetic Algorithm (RKGA)-based path optimization. The proposed RoboCoDraw system takes a real human face image as input, converts it to a stylized avatar, then draws it with a robotic arm. A core component in this system is the Avatar-GAN proposed by us, which generates a cartoon avatar face image from a real human face. AvatarGAN is trained with unpaired face and avatar images only and can generate avatar images of much better likeness with human face images in comparison with the vanilla CycleGAN. After the avatar image is generated, it is fed to a line extraction algorithm and converted to sketches. An RKGA-based path optimization algorithm is applied to find a time-efficient robotic drawing path to be executed by the robotic arm. We demonstrate the capability of RoboCoDraw on various face images using a lightweight, safe collaborative robot UR5., Comment: Accepted by AAAI2020

Gene-based testing is a commonly employed strategy in many genetic association studies. Gene-trait associations can be complex due to underlying population heterogeneity, gene-environment interactions, and various other reasons. Existing gene-based tests, such as Burden and Sequence Kernel Association Tests (SKAT), are based on detecting differences in a single summary statistic, such as the mean or the variance, and may miss or underestimate higher-order associations that could be scientifically interesting. In this paper, we propose a new family of gene-level association tests which integrate quantile rank score processes to better accommodate complex associations. The resulting test statistics have multiple advantages: (1) they are almost as efficient as the best existing tests when the associations are homogeneous across quantile levels, and have improved efficiency for complex and heterogeneous associations, (2) they provide useful insights on risk stratification, (3) the test statistics are distribution-free, and could hence accommodate a wide range of underlying distributions, and (4) they are computationally efficient. We established the asymptotic properties of the proposed tests under the null and alternative hypothesis and conducted large scale simulation studies to investigate their finite sample performance. We applied the proposed tests to the Metabochip data to identify genetic associations with lipid traits and compared the results with those of the Burden and SKAT tests.

Covariate measurement error in nonparametric regression is a common problem in nutritional epidemiology and geostatistics, and other fields. Over the last two decades, this problem has received substantial attention in the frequentist literature. Bayesian approaches for handling measurement error have only been explored recently and are surprisingly successful, although the lack of a proper theoretical justification regarding the asymptotic performance of the estimators. By specifying a Gaussian process prior on the regression function and a Dirichlet process Gaussian mixture prior on the unknown distribution of the unobserved covariates, we show that the posterior distribution of the regression function and the unknown covariates density attain optimal rates of contraction adaptively over a range of H\"{o}lder classes, up to logarithmic terms. This improves upon the existing classical frequentist results which require knowledge of the smoothness of the underlying function to deliver optimal risk bounds. We also develop a novel surrogate prior for approximating the Gaussian process prior that leads to efficient computation and preserves the covariance structure, thereby facilitating easy prior elicitation. We demonstrate the empirical performance of our approach and compare it with competitors in a wide range of simulation experiments and a real data example.

Standard logistic regression analysis of case-control data has low power to detect gene-environment interactions, but until recently it was the only method that could be used on complex polygenic data for which parametric distributional models are not feasible. Under the assumption of gene-environment independence in the underlying population, Stalder et al. (2017, Biometrika, 104, 801-812) developed a retrospective method that treats both genetic and environmental variables nonparametrically. However, the mathematical symmetry of genetic and environmental variables is overlooked. We propose an improvement to the method of Stalder et al. (2017) that increases the efficiency of the estimates with no additional assumptions and modest computational cost. This improvement is achieved by treating the genetic and environmental variables symmetrically to generate two sets of parameter estimates that are combined to generate a more efficient estimate. We employ a semiparametric framework to develop the asymptotic theory of the estimator, show its asymptotic efficiency gain, and evaluate its performance via simulation studies. The method is illustrated using data from a case-control study of breast cancer.

We consider the problem of high-dimensional classification between the two groups with unequal covariance matrices. Rather than estimating the full quadratic discriminant rule, we propose to perform simultaneous variable selection and linear dimension reduction on original data, with the subsequent application of quadratic discriminant analysis on the reduced space. In contrast to quadratic discriminant analysis, the proposed framework doesn't require estimation of precision matrices and scales linearly with the number of measurements, making it especially attractive for the use on high-dimensional datasets. We support the methodology with theoretical guarantees on variable selection consistency, and empirical comparison with competing approaches. We apply the method to gene expression data of breast cancer patients, and confirm the crucial importance of ESR1 gene in differentiating estrogen receptor status.