Dataset Information

Bootstrap Model-Based Constrained Optimization Tests of Indirect Effects.

ABSTRACT: In mediation analysis, conditions necessary for commonly recommended tests, including the confidence interval (CI)-based tests, to produce an accurate Type I error, do not generally hold for finite sample sizes and non-normally distributed model residuals. This is typically the case because of the complexity of testing a null hypothesis about indirect effects. To remedy these issues, we propose two extensions of the recently developed asymptotic Model-based Constrained Optimization (MBCO) likelihood ratio test (LRT), a promising new model comparison method for testing a general function of indirect effects. The proposed tests, semi-parametric and parametric bootstrap MBCO LRT are shown to yield a more accurate Type I error rate in smaller sample sizes and under various degrees of non-normality of the model residuals compared to the asymptotic MBCO LRT and the CI-based methods. We provide R script in the Supplemental Materials to perform all three MBCO LRTs.

SUBMITTER: Tofighi D

PROVIDER: S-EPMC6984355 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Bootstrap Model-Based Constrained Optimization Tests of Indirect Effects.

Tofighi Davood D

Frontiers in psychology 20200120

In mediation analysis, conditions necessary for commonly recommended tests, including the confidence interval (CI)-based tests, to produce an accurate Type I error, do not generally hold for finite sample sizes and non-normally distributed model residuals. This is typically the case because of the complexity of testing a null hypothesis about indirect effects. To remedy these issues, we propose two extensions of the recently developed asymptotic Model-based Constrained Optimization (MBCO) likeli ...[more]

PMID: 32038377

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Project description:BackgroundRecent advances in bioimaging and automated analysis methods have enabled the large-scale systematic analysis of cellular dynamics during the embryonic development of Caenorhabditis elegans. Most of these analyses have focused on cell lineage tracing rather than cell shape dynamics. Cell shape analysis requires cell membrane segmentation, which is challenging because of insufficient resolution and image quality. This problem is currently solved by complicated segmentation methods requiring laborious and time consuming parameter adjustments.ResultsOur new framework BCOMS (Biologically Constrained Optimization based cell Membrane Segmentation) automates the extraction of the cell shape of C. elegans embryos. Both the segmentation and evaluation processes are automated. To automate the evaluation, we solve an optimization problem under biological constraints. The performance of BCOMS was validated against a manually created ground truth of the 24-cell stage embryo. The average deviation of 25 cell shape features was 5.6%. The deviation was mainly caused by membranes parallel to the focal planes, which either contact the surfaces of adjacent cells or make no contact with other cells. Because segmentation of these membranes was difficult even by manual inspection, the automated segmentation was sufficiently accurate for cell shape analysis. As the number of manually created ground truths is necessarily limited, we compared the segmentation results between two adjacent time points. Across all cells and all cell cycles, the average deviation of the 25 cell shape features was 4.3%, smaller than that between the automated segmentation result and ground truth.ConclusionsBCOMS automated the accurate extraction of cell shapes in developing C. elegans embryos. By replacing image processing parameters with easily adjustable biological constraints, BCOMS provides a user-friendly framework. The framework is also applicable to other model organisms. Creating the biological constraints is a critical step requiring collaboration between an experimentalist and a software developer.

Project description:In many scientific studies, the underlying data-generating process is unknown and multiple statistical models are considered to describe it. For example, in a factorial experiment we might consider models involving just main effects, as well as those that include interactions. Model-averaging is a commonly-used statistical technique to allow for model uncertainty in parameter estimation. In the frequentist setting, the model-averaged estimate of a parameter is a weighted mean of the estimates from the individual models, with the weights typically being based on an information criterion, cross-validation, or bootstrapping. One approach to building a model-averaged confidence interval is to use a Wald interval, based on the model-averaged estimate and its standard error. This has been the default method in many application areas, particularly those in the life sciences. The MA-Wald interval, however, assumes that the studentized model-averaged estimate has a normal distribution, which can be far from true in practice due to the random, data-driven model weights. Recently, the model-averaged tail area Wald interval (MATA-Wald) has been proposed as an alternative to the MA-Wald interval, which only assumes that the studentized estimate from each model has a N(0, 1) or t-distribution, when that model is true. This alternative to the MA-Wald interval has been shown to have better coverage in simulation studies. However, when we have a response variable that is skewed, even these relaxed assumptions may not be valid, and use of these intervals might therefore result in poor coverage. We propose a new interval (MATA-SBoot) which uses a parametric bootstrap approach to estimate the distribution of the studentized estimate for each model, when that model is true. This method only requires that the studentized estimate from each model is approximately pivotal, an assumption that will often be true in practice, even for skewed data. We illustrate use of this new interval in the analysis of a three-factor marine global change experiment in which the response variable is assumed to have a lognormal distribution. We also perform a simulation study, based on the example, to compare the lower and upper error rates of this interval with those for existing methods. The results suggest that the MATA-SBoot interval can provide better error rates than existing intervals when we have skewed data, particularly for the upper error rate when the sample size is small.

Dataset Information

Bootstrap Model-Based Constrained Optimization Tests of Indirect Effects.

Publications

Bootstrap Model-Based Constrained Optimization Tests of Indirect Effects.

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