The problem of how to best select variables for confounding adjustment forms one of the key challenges in the evaluation of exposure effects in observational studies, and has been the subject of vigorous recent activity in causal inference. A major drawback of routine procedures is that there is no finite sample size at which they are guaranteed to deliver exposure effect estimators and associated confidence intervals with adequate performance. In this work, we will consider this problem when inferring conditional causal hazard ratios from observational studies under the assumption of no unmeasured confounding. The major complication that we face with survival data is that the key confounding variables may not be those that explain the censoring mechanism. In this paper, we overcome this problem using a novel and simple procedure that can be implemented using off-the-shelf software for penalized Cox regression. In particular, we will propose tests of the null hypothesis that the exposure has no effect on the considered survival endpoint, which are uniformly valid under standard sparsity conditions. Simulation results show that the proposed methods yield valid inferences even when covariates are high-dimensional.
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We consider the statistical analysis of heterogeneous data for clustering and prediction purposes, in situations where the observations include functions, typically time series. We extend the modeling with Mixtures-of-Experts (ME), as a framework of choice in modeling heterogeneity in data for prediction and clustering with vectorial observations, to this functional data analysis context. We first present a new family of functional ME (FME) models, in which the predictors are potentially noisy observations, from entire functions, and the data generating process of the pair predictor and the real response, is governed by a hidden discrete variable representing an unknown partition, leading to complex situations to which the standard ME framework is not adapted. Second, we provide sparse and interpretable functional representations of the FME models, thanks to Lasso-like regularizations, notably on the derivatives of the underlying functional parameters of the model, projected onto a set of continuous basis functions. We develop dedicated expectation--maximization algorithms for Lasso-like regularized maximum-likelihood parameter estimation strategies, to encourage sparse and interpretable solutions. The proposed FME models and the developed EM-Lasso algorithms are studied in simulated scenarios and in applications to two real data sets, and the obtained results demonstrate their performance in accurately capturing complex nonlinear relationships between the response and the functional predictor, and in clustering.
We relate discrepancy theory with the classic scheduling problems of minimizing max flow time and total flow time on unrelated machines. Specifically, we give a general reduction that allows us to transfer discrepancy bounds in the prefix Beck-Fiala (bounded $\ell_1$-norm) setting to bounds on the flow time of an optimal schedule. Combining our reduction with a deep result proved by Banaszczyk via convex geometry, give guarantees of $O(\sqrt{\log n})$ and $O(\sqrt{\log n} \log P)$ for max flow time and total flow time, respectively, improving upon the previous best guarantees of $O(\log n)$ and $O(\log n \log P)$. Apart from the improved guarantees, the reduction motivates seemingly easy versions of prefix discrepancy questions: any constant bound on prefix Beck-Fiala where vectors have sparsity two (sparsity one being trivial) would already yield tight guarantees for both max flow time and total flow time. While known techniques solve this case when the entries take values in $\{-1,0,1\}$, we show that they are unlikely to transfer to the more general $2$-sparse case of bounded $\ell_1$-norm.
Missing data is a systemic problem in practical scenarios that causes noise and bias when estimating treatment effects. This makes treatment effect estimation from data with missingness a particularly tricky endeavour. A key reason for this is that standard assumptions on missingness are rendered insufficient due to the presence of an additional variable, treatment, besides the individual and the outcome. Having a treatment variable introduces additional complexity with respect to why some variables are missing that is not fully explored by previous work. In our work we identify a new missingness mechanism, which we term mixed confounded missingness (MCM), where some missingness determines treatment selection and other missingness is determined by treatment selection. Given MCM, we show that naively imputing all data leads to poor performing treatment effects models, as the act of imputation effectively removes information necessary to provide unbiased estimates. However, no imputation at all also leads to biased estimates, as missingness determined by treatment divides the population in distinct subpopulations, where estimates across these populations will be biased. Our solution is selective imputation, where we use insights from MCM to inform precisely which variables should be imputed and which should not. We empirically demonstrate how various learners benefit from selective imputation compared to other solutions for missing data.
In this paper we develop a likelihood-free approach for population calibration, which involves finding distributions of model parameters when fed through the model produces a set of outputs that matches available population data. Unlike most other approaches to population calibration, our method produces uncertainty quantification on the estimated distribution. Furthermore, the method can be applied to any population calibration problem, regardless of whether the model of interest is deterministic or stochastic, or whether the population data is observed with or without measurement error. We demonstrate the method on several examples, including one with real data. We also discuss the computational limitations of the approach. Immediate applications for the methodology developed here exist in many areas of medical research including cancer, COVID-19, drug development and cardiology.
We propose the Terminating-Knockoff (T-Knock) filter, a fast variable selection method for high-dimensional data. The T-Knock filter controls a user-defined target false discovery rate (FDR) while maximizing the number of selected variables. This is achieved by fusing the solutions of multiple early terminated random experiments. The experiments are conducted on a combination of the original predictors and multiple sets of randomly generated knockoff predictors. A finite sample proof based on martingale theory for the FDR control property is provided. Numerical simulations show that the FDR is controlled at the target level while allowing for a high power. We prove under mild conditions that the knockoffs can be sampled from any univariate probability distribution with existing finite expectation and variance. The computational complexity of the proposed method is derived and it is demonstrated via numerical simulations that the sequential computation time is multiple orders of magnitude lower than that of the strongest benchmark methods in sparse high-dimensional settings. The T-Knock filter outperforms state-of-the-art methods for FDR control on a simulated genome-wide association study (GWAS), while its computation time is more than two orders of magnitude lower than that of the strongest benchmark methods. An open source R package containing the implementation of the T-Knock filter is available at //github.com/jasinmachkour/tknock.
In this paper we give a completely new approach to the problem of covariate selection in linear regression. A covariate or a set of covariates is included only if it is better in the sense of least squares than the same number of Gaussian covariates consisting of i.i.d. $N(0,1)$ random variables. The Gaussian P-value is defined as the probability that the Gaussian covariates are better. It is given in terms of the Beta distribution, it is exact and it holds for all data making it model-free free. The covariate selection procedures require only a cut-off value $\alpha$ for the Gaussian P-value: the default value in this paper is $\alpha=0.01$. The resulting procedures are very simple, very fast, do not overfit and require only least squares. In particular there is no regularization parameter, no data splitting, no use of simulations, no shrinkage and no post selection inference is required. The paper includes the results of simulations, applications to real data sets and theorems on the asymptotic behaviour under the standard linear model. Here the step-wise procedure performs overwhelmingly better than any other procedure we are aware of. An R-package {\it gausscov} is available.
Black-box and preference-based optimization algorithms are global optimization procedures that aim to find the global solutions of an optimization problem using, respectively, the least amount of function evaluations or sample comparisons as possible. In the black-box case, the analytical expression of the objective function is unknown and it can only be evaluated through a (costly) computer simulation or an experiment. In the preference-based case, the objective function is still unknown but it corresponds to the subjective criterion of an individual. So, it is not possible to quantify such criterion in a reliable and consistent way. Therefore, preference-based optimization algorithms seek global solutions using only comparisons between couples of different samples, for which a human decision-maker indicates which of the two is preferred. Quite often, the black-box and preference-based frameworks are covered separately and are handled using different techniques. In this paper, we show that black-box and preference-based optimization problems are closely related and can be solved using the same family of approaches, namely surrogate-based methods. Moreover, we propose the generalized Metric Response Surface (gMRS) algorithm, an optimization scheme that is a generalization of the popular MSRS framework. Finally, we provide a convergence proof for the proposed optimization method.
A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential outcomes. The causal association paradigm assesses the relationship of the treatment effect on the surrogate with the treatment effect on the true endpoint. Using the principal surrogacy criteria, we utilize the joint conditional distribution of the potential outcomes T, given the potential outcomes S. In particular, our setting of interest allows us to assume the surrogate under the placebo, S(0), is zero-valued, and we incorporate baseline covariates in the setting of normally-distributed endpoints. We develop Bayesian methods to incorporate conditional independence and other modeling assumptions and explore their impact on the assessment of surrogacy. We demonstrate our approach via simulation and data that mimics an ongoing study of a muscular dystrophy gene therapy.
The availability of large microarray data has led to a growing interest in biclustering methods in the past decade. Several algorithms have been proposed to identify subsets of genes and conditions according to different similarity measures and under varying constraints. In this paper we focus on the exclusive row biclustering problem for gene expression data sets, in which each row can only be a member of a single bicluster while columns can participate in multiple ones. This type of biclustering may be adequate, for example, for clustering groups of cancer patients where each patient (row) is expected to be carrying only a single type of cancer, while each cancer type is associated with multiple (and possibly overlapping) genes (columns). We present a novel method to identify these exclusive row biclusters through a combination of existing biclustering algorithms and combinatorial auction techniques. We devise an approach for tuning the threshold for our algorithm based on comparison to a null model in the spirit of the Gap statistic approach. We demonstrate our approach on both synthetic and real-world gene expression data and show its power in identifying large span non-overlapping rows sub matrices, while considering their unique nature. The Gap statistic approach succeeds in identifying appropriate thresholds in all our examples.
We consider the task of learning the parameters of a {\em single} component of a mixture model, for the case when we are given {\em side information} about that component, we call this the "search problem" in mixture models. We would like to solve this with computational and sample complexity lower than solving the overall original problem, where one learns parameters of all components. Our main contributions are the development of a simple but general model for the notion of side information, and a corresponding simple matrix-based algorithm for solving the search problem in this general setting. We then specialize this model and algorithm to four common scenarios: Gaussian mixture models, LDA topic models, subspace clustering, and mixed linear regression. For each one of these we show that if (and only if) the side information is informative, we obtain parameter estimates with greater accuracy, and also improved computation complexity than existing moment based mixture model algorithms (e.g. tensor methods). We also illustrate several natural ways one can obtain such side information, for specific problem instances. Our experiments on real data sets (NY Times, Yelp, BSDS500) further demonstrate the practicality of our algorithms showing significant improvement in runtime and accuracy.
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