Author(s): Zhang, Yuqian; Bradic, Jelena | Abstract: We provide a high-dimensional semi-supervised inference framework focused on the mean and variance of the response. Our data are comprised of an extensive set of observations regarding the covariate vectors and a much smaller set of labeled observations where we observe both the response as well as the covariates. We allow the size of the covariates to be much larger than the sample size and impose weak conditions on a statistical form of the data. We provide new estimators of the mean and variance of the response that extend some of the recent results presented in low-dimensional models. In particular, at times we will not necessitate consistent estimation of the functional form of the data. Together with estimation of the population mean and variance, we provide their asymptotic distribution and confidence intervals where we showcase gains in efficiency compared to the sample mean and variance. Our procedure, with minor modifications, is then presented to make important contributions regarding inference about average treatment effects. We also investigate the robustness of estimation and coverage and showcase widespread applicability and generality of the proposed method.
 We consider statistical inference for the explained variance @math under the high-dimensional linear model @math in the semi-supervised setting, where @math is the regression vector and @math is the design covariance matrix. A calibrated estimator, which efficiently integrates both labelled and unlabelled data, is proposed. It is shown that the estimator achieves the minimax optimal rate of convergence in the general semi-supervised framework. The optimality result characterizes how the unlabelled data affects the minimax optimal rate. Moreover, the limiting distribution for the proposed estimator is established and data-driven confidence intervals for the explained variance are constructed. We further develop a randomized calibration technique for statistical inference in the presence of weak signals and apply the obtained inference results to a range of important statistical problems, including signal detection and global testing, prediction accuracy evaluation, and confidence ball construction. The numerical performance of the proposed methodology is demonstrated in simulation studies and an analysis of estimating heritability for a yeast segregant data set with multiple traits.   In many modern machine learning applications, the outcome is expensive or time consuming to collect whereas the predictor information is easy to obtain. Semiâ€ supervised (SS) learning aims at utilizing large amounts of â€˜unlabelledâ€™ data along with small amounts of â€˜labelledâ€™ data to improve the efficiency of a classical supervised approach. Though numerous SS learning classification and prediction procedures have been proposed in recent years, no methods currently exist to evaluate the prediction performance of a working regression model. In the context of developing phenotyping algorithms derived from electronic medical records, we present an efficient twoâ€ step estimation procedure for evaluating a binary classifier based on various prediction performance measures in the SS setting. In step I, the labelled data are used to obtain a nonâ€ parametrically calibrated estimate of the conditional risk function. In step II, SS estimates of the prediction accuracy parameters are constructed based on the estimated conditional risk function and the unlabelled data. We demonstrate that, under mild regularity conditions, the estimators proposed are consistent and asymptotically normal. Importantly, the asymptotic variance of the SS estimators is always smaller than that of the supervised counterparts under correct model specification. We also correct for potential overfitting bias in the SS estimators in finite samples with crossâ€ validation and we develop a perturbation resampling procedure to approximate their distributions. Our proposals are evaluated through extensive simulation studies and illustrated with two real electronic medical record studies aiming to develop phenotyping algorithms for rheumatoid arthritis and multiple sclerosis. We consider semi-supervised regression when the predictor variables are drawn from an unknown manifold. A simple two step approach to this problem is to: (i) estimate the manifold geodesic distance between any pair of points using both the labeled and unlabeled instances; and (ii) apply a k nearest neighbor regressor based on these distance estimates. We prove that given sufficiently many unlabeled points, this simple method of geodesic kNN regression achieves the optimal finite-sample minimax bound on the mean squared error, as if the manifold were known. Furthermore, we show how this approach can be efficiently implemented, requiring only O(k N log N) operations to estimate the regression function at all N labeled and unlabeled points. We illustrate this approach on two datasets with a manifold structure: indoor localization using WiFi fingerprints and facial pose estimation. In both cases, geodesic kNN is more accurate and much faster than the popular Laplacian eigenvector regressor. Given a weighted graph with N vertices, consider a real-valued regression problem in a semisupervised setting, where one observes n labeled vertices, and the task is to label the remaining ones. We present a theoretical study of p-based Laplacian regularization under a d-dimensional geometric random graph model. We provide a variational characterization of the performance of this regularized learner as N grows to infinity while n stays constant; the associated optimality conditions lead to a partial differential equation that must be satisfied by the associated function estimate f . From this formulation we derive several predictions on the limiting behavior the function f , including (a) a phase transition in its smoothness at the threshold p = d + 1; and (b) a tradeoff between smoothness and sensitivity to the underlying unlabeled data distribution P . Thus, over the range p ≤ d, the function estimate f is degenerate and “spiky,” whereas for p ≥ d + 1, the function estimate f is smooth. We show that the effect of the underlying density vanishes monotonically with p, such that in the limit p = ∞, corresponding to the so-called Absolutely Minimal Lipschitz Extension, the estimate f is independent of the distribution P . Under the assumption of semi-supervised smoothness, ignoring P can lead to poor statistical performance; in particular, we construct a specific example for d = 1 to demonstrate that p = 2 has lower risk than p =∞ due to the former penalty adapting to P and the latter ignoring it. We also provide simulations that verify the accuracy of our predictions for finite sample sizes. Together, these properties show that p = d + 1 is an optimal choice, yielding a function estimate f that is both smooth and non-degenerate, while remaining maximally sensitive to P . Semi-supervised methods use unlabeled data in addition to labeled data to construct predictors. While existing semi-supervised methods have shown some promising empirical performance, their development has been based largely based on heuristics. In this paper we study semi-supervised learning from the viewpoint of minimax theory. Our first result shows that some common methods based on regularization using graph Laplacians do not lead to faster minimax rates of convergence. Thus, the estimators that use the unlabeled data do not have smaller risk than the estimators that use only labeled data. We then develop several new approaches that provably lead to improved performance. The statistical tools of minimax analysis are thus used to offer some new perspective on the problem of semi-supervised learning. There is strong interest in conducting comparative effectiveness research (CER) in electronic medical records (EMR) to evaluate treatment strategies among real-world patients. Inferring causal effects in EMR data, however, is challenging due to the lack of direct observation on pre-specified gold-standard outcomes, in addition to the observational nature of the data. Extracting gold-standard outcomes often requires labor-intensive medical chart review, which is unfeasible for large studies. While one may impute outcomes and estimate average treatment effects (ATE) based on imputed data, naive imputations may lead to biased ATE estimators. In this paper, we frame the problem of estimating the ATE in a semi-supervised learning setting, where a small set of observations is labeled with the true outcome via manual chart review and a large set of unlabeled observations with features predictive of the outcome are available. We develop an imputation-based approach for estimating the ATE that is robust to misspecification of the imputation model. This allows information from the predictive features to be safely leveraged to improve the efficiency in estimating the ATE. The estimator is additionally doubly-robust in that it is consistent under correct specification of either an initial propensity score model or a baseline outcome model. We show that it is locally semiparametric efficient under an ideal semi-supervised model where the distribution of unlabeled data is known. Simulations exhibit the efficiency and robustness of the proposed method compared to existing approaches in finite samples. We illustrate the method to compare rates of treatment response to two biologic agents for treating inflammatory bowel disease using EMR data from Partner's Healthcare. We consider the semi-supervised learning problem, where a decision rule is to be learned from labeled and unlabeled data. In this framework, we motivate minimum entropy regularization, which enables to incorporate unlabeled data in the standard supervised learning. Our approach includes other approaches to the semi-supervised problem as particular or limiting cases. A series of experiments illustrates that the proposed solution benefits from unlabeled data. The method challenges mixture models when the data are sampled from the distribution class spanned by the generative model. The performances are definitely in favor of minimum entropy regularization when generative models are misspecified, and the weighting of unlabeled data provides robustness to the violation of the "cluster assumption". Finally, we also illustrate that the method can also be far superior to manifold learning in high dimension spaces. We consider the linear regression problem under semi-supervised settings wherein the available data typically consists of: (i) a small or moderate sized 'labeled' data, and (ii) a much larger sized 'unlabeled' data. Such data arises naturally from settings where the outcome, unlike the covariates, is expensive to obtain, a frequent scenario in modern studies involving large databases like electronic medical records (EMR). Supervised estimators like the ordinary least squares (OLS) estimator utilize only the labeled data. It is often of interest to investigate if and when the unlabeled data can be exploited to improve estimation of the regression parameter in the adopted linear model. In this paper, we propose a class of 'Efficient and Adaptive Semi-Supervised Estimators' (EASE) to improve estimation efficiency. The EASE are two-step estimators adaptive to model mis-specification, leading to improved (optimal in some cases) efficiency under model mis-specification, and equal (optimal) efficiency under a linear model. This adaptive property, often unaddressed in the existing literature, is crucial for advocating 'safe' use of the unlabeled data. The construction of EASE primarily involves a flexible 'semi-non-parametric' imputation, including a smoothing step that works well even when the number of covariates is not small; and a follow up 'refitting' step along with a cross-validation (CV) strategy both of which have useful practical as well as theoretical implications towards addressing two important issues: under-smoothing and over-fitting. We establish asymptotic results including consistency, asymptotic normality and the adaptive properties of EASE. We also provide influence function expansions and a 'double' CV strategy for inference. The results are further validated through extensive simulations, followed by application to an EMR study on auto-immunity.