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The widespread availability of high-dimensional biological data has made the simultaneous screening of many biological characteristics a central problem in computational biology and allied sciences. While the dimensionality of such datasets continues to grow, so too does the complexity of biomarker identification from exposure patterns in health studies measuring baseline confounders; moreover, doing so while avoiding model misspecification remains an issue only partially addressed. Efficient estimators capable of incorporating flexible, data adaptive regression techniques in estimating relevant components of the data-generating distribution provide an avenue for avoiding model misspecification; however, in the context of high-dimensional problems that require the simultaneous estimation of numerous parameters, standard variance estimators have proven unstable, resulting in unreliable Type-I error control even under standard multiple testing corrections. We present a general approach for applying empirical Bayes shrinkage to variance estimators of a family of efficient, asymptotically linear estimators of population intervention causal effects. Our generalization of shrinkage-based variance estimators increases inferential stability in high-dimensional settings, facilitating the application of these estimators for deriving nonparametric variable importance measures in high-dimensional biological datasets with modest sample sizes. The result is a data adaptive approach for robustly uncovering stable causal associations in high-dimensional data in studies with limited samples. Our generalized variance estimator is evaluated against alternative variance estimators in numerical experiments. Identification of biomarkers with the proposed methodology is demonstrated in an analysis of high-dimensional DNA methylation data from an observational study on the epigenetic effects of tobacco smoking.

Network-based clustering methods frequently require the number of communities to be specified \emph{a priori}. Moreover, most of the existing methods for estimating the number of communities assume the number of communities to be fixed and not scale with the network size $n$. The few methods that assume the number of communities to increase with the network size $n$ are only valid when the average degree $d$ of a network grows at least as fast as $O(n)$ (i.e., the dense case) or lies within a narrow range. This presents a challenge in clustering large-scale network data, particularly when the average degree $d$ of a network grows slower than the rate of $O(n)$ (i.e., the sparse case). To address this problem, we proposed a new sequential procedure utilizing multiple hypothesis tests and the spectral properties of Erd\"{o}s R\'{e}nyi graphs for estimating the number of communities in sparse stochastic block models (SBMs). We prove the consistency of our method for sparse SBMs for a broad range of the sparsity parameter. As a consequence, we discover that our method can estimate the number of communities $K^{(n)}_{\star}$ with $K^{(n)}_{\star}$ increasing at the rate as high as $O(n^{(1 - 3\gamma)/(4 - 3\gamma)})$, where $d = O(n^{1 - \gamma})$. Moreover, we show that our method can be adapted as a stopping rule in estimating the number of communities in binary tree stochastic block models. We benchmark the performance of our method against other competing methods on six reference single-cell RNA sequencing datasets. Finally, we demonstrate the usefulness of our method through numerical simulations and by using it for clustering real single-cell RNA-sequencing datasets.

The classical statistical learning theory says that fitting too many parameters leads to overfitting and poor performance. That modern deep neural networks generalize well despite a large number of parameters contradicts this finding and constitutes a major unsolved problem towards explaining the success of deep learning. The implicit regularization induced by stochastic gradient descent (SGD) has been regarded to be important, but its specific principle is still unknown. In this work, we study how the local geometry of the energy landscape around local minima affects the statistical properties of SGD with Gaussian gradient noise. We argue that under reasonable assumptions, the local geometry forces SGD to stay close to a low dimensional subspace and that this induces implicit regularization and results in tighter bounds on the generalization error for deep neural networks. To derive generalization error bounds for neural networks, we first introduce a notion of stagnation sets around the local minima and impose a local essential convexity property of the population risk. Under these conditions, lower bounds for SGD to remain in these stagnation sets are derived. If stagnation occurs, we derive a bound on the generalization error of deep neural networks involving the spectral norms of the weight matrices but not the number of network parameters. Technically, our proofs are based on controlling the change of parameter values in the SGD iterates and local uniform convergence of the empirical loss functions based on the entropy of suitable neighborhoods around local minima. Our work attempts to better connect non-convex optimization and generalization analysis with uniform convergence.

Estimating and reacting to external disturbances is of fundamental importance for robust control of quadrotors. Existing estimators typically require significant tuning or training with a large amount of data, including the ground truth, to achieve satisfactory performance. This paper proposes a data-efficient differentiable moving horizon estimation (DMHE) algorithm that can automatically tune the MHE parameters online and also adapt to different scenarios. We achieve this by deriving the analytical gradient of the estimated trajectory from MHE with respect to the tuning parameters, enabling end-to-end learning for auto-tuning. Most interestingly, we show that the gradient can be calculated efficiently from a Kalman filter in a recursive form. Moreover, we develop a model-based policy gradient algorithm to learn the parameters directly from the trajectory tracking errors without the need for the ground truth. The proposed DMHE can be further embedded as a layer with other neural networks for joint optimization. Finally, we demonstrate the effectiveness of the proposed method via both simulation and experiments on quadrotors, where challenging scenarios such as sudden payload change and flying in downwash are examined.

In this paper, we present a sharp analysis for a class of alternating projected gradient descent algorithms which are used to solve the covariate adjusted precision matrix estimation problem in the high-dimensional setting. We demonstrate that these algorithms not only enjoy a linear rate of convergence in the absence of convexity, but also attain the optimal statistical rate (i.e., minimax rate). By introducing the generic chaining, our analysis removes the impractical resampling assumption used in the previous work. Moreover, our results also reveal a time-data tradeoff in this covariate adjusted precision matrix estimation problem. Numerical experiments are provided to verify our theoretical results.

We propose a new method for multivariate response regression and covariance estimation when elements of the response vector are of mixed types, for example some continuous and some discrete. Our method is based on a model which assumes the observable mixed-type response vector is connected to a latent multivariate normal response linear regression through a link function. We explore the properties of this model and show its parameters are identifiable under reasonable conditions. We impose no parametric restrictions on the covariance of the latent normal other than positive definiteness, thereby avoiding assumptions about unobservable variables which can be difficult to verify in practice. To accommodate this generality, we propose a novel algorithm for approximate maximum likelihood estimation that works "off-the-shelf" with many different combinations of response types, and which scales well in the dimension of the response vector. Our method typically gives better predictions and parameter estimates than fitting separate models for the different response types and allows for approximate likelihood ratio testing of relevant hypotheses such as independence of responses. The usefulness of the proposed method is illustrated in simulations; and one biomedical and one genomic data example.

In the group testing problem, the goal is to identify a subset of defective items within a larger set of items based on tests whose outcomes indicate whether any defective item is present. This problem is relevant in areas such as medical testing, DNA sequencing, and communications. In this paper, we study a doubly-regular design in which the number of tests-per-item and the number of items-per-test are fixed. We analyze the performance of this test design alongside the Definite Defectives (DD) decoding algorithm in several settings, namely, (i) the sub-linear regime $k=o(n)$ with exact recovery, (ii) the linear regime $k=\Theta(n)$ with approximate recovery, and (iii) the size-constrained setting, where the number of items per test is constrained. Under setting (i), we show that our design together with the DD algorithm, matches an existing achievability result for the DD algorithm with the near-constant tests-per-item design, which is known to be asymptotically optimal in broad scaling regimes. Under setting (ii), we provide novel approximate recovery bounds that complement a hardness result regarding exact recovery. Lastly, under setting (iii), we improve on the best known upper and lower bounds in scaling regimes where the maximum allowed test size grows with the total number of items.

Proximal Policy Optimization (PPO) is a highly popular model-free reinforcement learning (RL) approach. However, in continuous state and actions spaces and a Gaussian policy -- common in computer animation and robotics -- PPO is prone to getting stuck in local optima. In this paper, we observe a tendency of PPO to prematurely shrink the exploration variance, which naturally leads to slow progress. Motivated by this, we borrow ideas from CMA-ES, a black-box optimization method designed for intelligent adaptive Gaussian exploration, to derive PPO-CMA, a novel proximal policy optimization approach that can expand the exploration variance on objective function slopes and shrink the variance when close to the optimum. This is implemented by using separate neural networks for policy mean and variance and training the mean and variance in separate passes. Our experiments demonstrate a clear improvement over vanilla PPO in many difficult OpenAI Gym MuJoCo tasks.

Large margin nearest neighbor (LMNN) is a metric learner which optimizes the performance of the popular $k$NN classifier. However, its resulting metric relies on pre-selected target neighbors. In this paper, we address the feasibility of LMNN's optimization constraints regarding these target points, and introduce a mathematical measure to evaluate the size of the feasible region of the optimization problem. We enhance the optimization framework of LMNN by a weighting scheme which prefers data triplets which yield a larger feasible region. This increases the chances to obtain a good metric as the solution of LMNN's problem. We evaluate the performance of the resulting feasibility-based LMNN algorithm using synthetic and real datasets. The empirical results show an improved accuracy for different types of datasets in comparison to regular LMNN.

In this paper, we study the optimal convergence rate for distributed convex optimization problems in networks. We model the communication restrictions imposed by the network as a set of affine constraints and provide optimal complexity bounds for four different setups, namely: the function $F(\xb) \triangleq \sum_{i=1}^{m}f_i(\xb)$ is strongly convex and smooth, either strongly convex or smooth or just convex. Our results show that Nesterov's accelerated gradient descent on the dual problem can be executed in a distributed manner and obtains the same optimal rates as in the centralized version of the problem (up to constant or logarithmic factors) with an additional cost related to the spectral gap of the interaction matrix. Finally, we discuss some extensions to the proposed setup such as proximal friendly functions, time-varying graphs, improvement of the condition numbers.