Regression models allow one to isolate the relationship between the outcome and an explanatory variable while the other variables are held constant. Here, we introduce an R package, visreg, for the convenient visualization of this relationship via short, simple function calls. In addition to estimates of this relationship, the package also provides pointwise confidence bands and partial residuals to allow assessment of variability as well as outliers and other deviations from modeling assumptions. The package provides several options for visualizing models with interactions, including lattice plots, contour plots, and both static and interactive perspective plots. The implementation of the package is designed to be fully object-oriented and interface seamlessly with R's rich collection of model classes, allowing a consistent interface for visualizing not only linear models, but generalized linear models, proportional hazards models, generalized additive models, robust regression models, and many more.

We introduce the R package npmv that performs nonparametric inference for the comparison of multivariate data samples and provides the results in easy-to-understand, but statistically correct, language. Unlike in classical multivariate analysis of variance, multivariate normality is not required for the data. In fact, the different response variables may even be measured on different scales (binary, ordinal, quantitative). p values are calculated for overall tests (permutation tests and F approximations), and, using multiple testing algorithms which control the familywise error rate, significant subsets of response variables and factor levels are identified. The package may be used for low-or highdimensional data with small or with large sample sizes and many or few factor levels.

Pairwise‐based methods such as the free energy perturbation (FEP) method have been widely deployed to compute the binding free energy differences between two similar host–guest complexes. The calculated pairwise free energy difference is either directly adopted or transformed to absolute binding free energy for molecule rank ordering. We investigated, through both analytic derivations and simulations, how the selection of pairs in the experiment could impact the overall prediction precision. Our studies showed that (1) the estimated absolute binding free energy (truenormalΔG^) derived from calculated pairwise differences (ΔΔG) through weighted least squares fitting is more precise in prediction than the pairwise difference values when the number of pairs is more than the number of ligands and (2) prediction precision is influenced by both the total number of pairs and the specifically selected pairs, the latter being critically important when the number of calculated pairs is limited. Furthermore, we applied optimal experimental design in pair selection and found that the optimally selected pairs can outperform randomly selected pairs in prediction precision. In an illustrative example, we showed that, upon weighing ligand structure similarity into design optimization, the weighted optimal designs are more efficient than the literature reported designs. This work provides a new approach to assess retrospective pairwise‐based prediction results, and a method to design new prospective pairwise‐based experiments for molecular lead optimization. © 2019 Wiley Periodicals, Inc.

Summary Generalized estimating equations (GEE) are often used for the marginal analysis of longitudinal data. Although much work has been done to improve the validity of GEE for the analysis of data arising from small-sample studies, little attention has been given to power in such settings. Therefore, we propose a valid GEE approach to improve power in small-sample longitudinal study settings in which the temporal spacing of outcomes is the same for each subject. Specifically, we use a modified empirical sandwich covariance matrix estimator within correlation structure selection criteria and test statistics. Use of this estimator can improve the accuracy of selection criteria and increase the degrees of freedom to be used for inference. The resulting impacts on power are demonstrated via a simulation study and application example.

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