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Register a new userPairwise comparison of treatment levels in functional analysis of variance with application to erythrocyte hemolysis
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Added by
Olga Vsevolozhskaya
Publication date
2014
fields
Mathematical Statistics
and research's language is
English
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Motivated by a practical need for the comparison of hemolysis curves at various treatment levels, we propose a novel method for pairwise comparison of mean functional responses. The hemolysis curves - the percent hemolysis as a function of time - of mice erythrocytes (red blood cells) by hydrochloric acid have been measured among different treatment levels. This data set fits well within the functional data analysis paradigm, in which a time series is considered as a realization of the underlying stochastic process or a smooth curve. Previous research has only provided methods for identifying some differences in mean curves at different times. We propose a two-level follow-up testing framework to allow comparisons of pairs of treatments within regions of time where some difference among curves is identified. The closure multiplicity adjustment method is used to control the family-wise error rate of the proposed procedure.
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The association between a persons physical activity and various health outcomes is an area of active research. The National Health and Nutrition Examination Survey (NHANES) data provide a valuable resource for studying these associations. NHANES accelerometry data has been used by many to measure individuals activity levels. A common approach for analyzing accelerometry data is functional principal component analysis (FPCA). The first part of the paper uses Poisson FPCA (PFPCA), Gaussian FPCA (GFPCA), and nonnegative and regularized function decomposition (NARFD) to extract features from the count-valued NHANES accelerometry data. The second part of the paper compares logistic regression, random forests, and AdaBoost models based on GFPCA, NARFD, or PFPCA scores in the context of mortality prediction. The results show that Poisson FPCA is the best FPCA model for the inference of accelerometry data, and the AdaBoost model based on Poisson FPCA scores gives the best mortality prediction results.
Lung cancer is among the most common cancers in the United States, in terms of incidence and mortality. In 2009, it is estimated that more than 150,000 deaths will result from lung cancer alone. Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Over the past several years, investigators have conducted numerous association studies where intensive genetic data is collected on relatively few patients compared to the numbers of gene predictors, with one scientific goal being to identify genetic features associated with cancer recurrence or survival. In this note, we propose high-dimensional survival analysis through a new application of boosting, a powerful tool in machine learning. Our approach is based on an accelerated lifetime model and minimizing the sum of pairwise differences in residuals. We apply our method to a recent microarray study of lung adenocarcinoma and find that our ensemble is composed of 19 genes, while a proportional hazards (PH) ensemble is composed of nine genes, a proper subset of the 19-gene panel. In one of our simulation scenarios, we demonstrate that PH boosting in a misspecified model tends to underfit and ignore moderately-sized covariate effects, on average. Diagnostic analyses suggest that the PH assumption is not satisfied in the microarray data and may explain, in part, the discrepancy in the sets of active coefficients. Our simulation studies and comparative data analyses demonstrate how statistical learning by PH models alone is insufficient.
Motivated by increasing trends of relating brain images to a clinical outcome of interest, we propose a functional domain selection (FuDoS) method that effectively selects subregions of the brain associated with the outcome. View each individuals brain as a 3D functional object, the statistical aim is to distinguish the region where a regression coefficient $beta(t)=0$ from $beta(t) eq0$, where $t$ denotes spatial location. FuDoS is composed of two stages of estimation. We first segment the brain into several small parts based on the correlation structure. Then, potential subsets are built using the obtained segments and their predictive performance are evaluated to select the best subset, augmented by a stability selection criterion. We conduct extensive simulations both for 1D and 3D functional data, and evaluate its effectiveness in selecting the true subregion. We also investigate predictive ability of the selected stable regions. To find the brain regions related to cognitive ability, FuDoS is applied to the ADNIs PET data. Due to the induced sparseness, the results naturally provide more interpretable information about the relations between the regions and the outcome. Moreover, the selected regions from our analysis show high associations with the expected anatomical brain areas known to have memory-related functions.
No unmeasured confounding is often assumed in estimating treatment effects in observational data when using approaches such as propensity scores and inverse probability weighting. However, in many such studies due to the limitation of the databases, collected confounders are not exhaustive, and it is crucial to examine the extent to which the resulting estimate is sensitive to the unmeasured confounders. We consider this problem for survival and competing risks data. Due to the complexity of models for such data, we adapt the simulated potential confounders approach of Carnegie et al. (2016), which provides a general tool for sensitivity analysis due to unmeasured confounding. More specifically, we specify one sensitivity parameter to quantify the association between an unmeasured confounder and the treatment assignment, and another set of parameters to quantify the association between the confounder and the time-to-event outcomes. By varying the magnitudes of the sensitivity parameters, we estimate the treatment effect of interest using the stochastic EM and the EM algorithms. We demonstrate the performance of our methods on simulated data, and apply them to a comparative effectiveness study in inflammatory bowel disease (IBD).
Motivated by the analysis of high-dimensional neuroimaging signals located over the cortical surface, we introduce a novel Principal Component Analysis technique that can handle functional data located over a two-dimensional manifold. For this purpose a regularization approach is adopted, introducing a smoothing penalty coherent with the geodesic distance over the manifold. The model introduced can be applied to any manifold topology, can naturally handle missing data and functional samples evaluated in different grids of points. We approach the discretization task by means of finite element analysis and propose an efficient iterative algorithm for its resolution. We compare the performances of the proposed algorithm with other approaches classically adopted in literature. We finally apply the proposed method to resting state functional magnetic resonance imaging data from the Human Connectome Project, where the method shows substantial differential variations between brain regions that were not apparent with other approaches.
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