arXiv subjects

Magne Thoresen

Publications and source records attributed to Magne Thoresen.

23 records · Page 2Linked to original sources

arXiv2019

Optimal two-stage testing of multiple mediators

Mediation analysis in high-dimensional settings often involves identifying potential mediators among a large number of measured variables. For this purpose, a two step familywise error rate (FWER) procedure called ScreenMin has been recently proposed (Djordjilović et al. 2019). In ScreenMin, variables are first screened and only those that pass the screening are tested. The proposed threshold for selection has been shown to guarantee asymptotic FWER. In this work, we investigate the impact of the selection threshold on the finite sample FWER. We derive power maximizing selection threshold and show that it is well approximated by an adaptive threshold of Wang et al. (2016). We study the performance of the proposed procedures in a simulation study, and apply them to a case-control study examining the effect of fish intake on the risk of colorectal adenoma.

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arXiv2016

Non-Concave Penalization in Linear Mixed-Effects Models and Regularized Selection of Fixed Effects

Mixed-effect models are very popular for analyzing data with a hierarchical structure, e.g. repeated observations within subjects in a longitudinal design, patients nested within centers in a multicenter design. However, recently, due to the medical advances, the number of fixed effect covariates collected from each patient can be quite large, e.g. data on gene expressions of each patient, and all of these variables are not necessarily important for the outcome. So, it is very important to choose the relevant covariates correctly for obtaining the optimal inference for the overall study. On the other hand, the relevant random effects will often be low-dimensional and pre-specified. In this paper, we consider regularized selection of important fixed effect variables in linear mixed-effects models along with maximum penalized likelihood estimation of both fixed and random effect parameters based on general non-concave penalties. Asymptotic and variable selection consistency with oracle properties are proved for low-dimensional cases as well as for high-dimensionality of non-polynomial order of sample size (number of parameters is much larger than sample size). We also provide a suitable computationally efficient algorithm for implementation. Additionally, all the theoretical results are proved for a general non-convex optimization problem that applies to several important situations well beyond the mixed model set-up (like finite mixture of regressions etc.) illustrating the huge range of applicability of our proposal.

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arXiv2014

Integrative clustering of high-dimensional data with joint and individual clusters, with an application to the Metabric study

When measuring a range of different genomic, epigenomic, transcriptomic and other variables, an integrative approach to analysis can strengthen inference and give new insights. This is also the case when clustering patient samples, and several integrative cluster procedures have been proposed. Common for these methodologies is the restriction of a joint cluster structure, which is equal for all data layers. We instead present Joint and Individual Clustering (JIC), which estimates both joint and data type-specific clusters simultaneously, as an extension of the JIVE algorithm (Lock et. al, 2013). The method is compared to iCluster, another integrative clustering method, and simulations show that JIC is clearly advantageous when both individual and joint clusters are present. The method is used to cluster patients in the Metabric study, integrating gene expression data and copy number aberrations (CNA). The analysis suggests a division into three joint clusters common for both data types and seven independent clusters specific for CNA. Both the joint and CNA-specific clusters are significantly different with respect to survival, also when adjusting for age and treatment.

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arXiv2014

Covariate Selection in High-Dimensional Generalized Linear Models With Measurement Error

In many problems involving generalized linear models, the covariates are subject to measurement error. When the number of covariates p exceeds the sample size n, regularized methods like the lasso or Dantzig selector are required. Several recent papers have studied methods which correct for measurement error in the lasso or Dantzig selector for linear models in the p>n setting. We study a correction for generalized linear models based on Rosenbaum and Tsybakov's matrix uncertainty selector. By not requiring an estimate of the measurement error covariance matrix, this generalized matrix uncertainty selector has a great practical advantage in problems involving high-dimensional data. We further derive an alternative method based on the lasso, and develop efficient algorithms for both methods. In our simulation studies of logistic and Poisson regression with measurement error, the proposed methods outperform the standard lasso and Dantzig selector with respect to covariate selection, by reducing the number of false positives considerably. We also consider classification of patients on the basis of gene expression data with noisy measurements.

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arXiv2014

Measurement Error in Lasso: Impact and Correction

Regression with the lasso penalty is a popular tool for performing dimension reduction when the number of covariates is large. In many applications of the lasso, like in genomics, covariates are subject to measurement error. We study the impact of measurement error on linear regression with the lasso penalty, both analytically and in simulation experiments. A simple method of correction for measurement error in the lasso is then considered. In the large sample limit, the corrected lasso yields sign consistent covariate selection under conditions very similar to the lasso with perfect measurements, whereas the uncorrected lasso requires much more stringent conditions on the covariance structure of the data. Finally, we suggest methods to correct for measurement error in generalized linear models with the lasso penalty, which we study empirically in simulation experiments with logistic regression, and also apply to a classification problem with microarray data. We see that the corrected lasso selects less false positives than the standard lasso, at a similar level of true positives. The corrected lasso can therefore be used to obtain more conservative covariate selection in genomic analysis.

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