The two main topics of this article are the introduction of the “optimally tuned robust improper maximum likelihood estimator” (OTRIMLE) for robust clustering based on the multivariate Gaussian model for clusters, and a comprehensive simulation study comparing the OTRIMLE to maximum likelihood in Gaussian mixtures with and without noise component, mixtures of t-distributions, and the TCLUST approach for trimmed clustering. The OTRIMLE uses an improper constant density for modeling outliers and noise. This can be chosen optimally so that the nonnoise part of the data looks as close to a Gaussian mixture as possible. Some deviation from Gaussianity can be traded in for lowering the estimated noise proportion. Covariance matrix constraints and computation of the OTRIMLE are also treated. In the simulation study, all methods are confronted with setups in which their model assumptions are not exactly fulfilled, and to evaluate the experiments in a standardized way by misclassification rates, a new model-based definition of “true clusters” is introduced that deviates from the usual identification of mixture components with clusters. In the study, every method turns out to be superior for one or more setups, but the OTRIMLE achieves the most satisfactory overall performance. The methods are also applied to two real datasets, one without and one with known “true” clusters. Supplementary materials for this article are available online.

Traditional quantitative structure-activity relationship models usually neglect the molecular alterations happening in the exposed systems (the mechanism of action, MOA), that mediate between structural properties of compounds and phenotypic effects of an exposure. Here, we propose a computational strategy that integrates molecular descriptors and MOA information to better explain the mechanisms underlying biological endpoints of interest. By applying our methodology, we obtained a statistically robust and validated model to predict the binding affinity to human serum albumin. Our model is also able to provide new venues for the interpretation of the chemical-biological interactions. Our observations suggest that integrated quantitative models of structural and MOA-activity relationships are promising complementary tools in the arsenal of strategies aiming at developing new safe- and useful-by-design compounds.

Summary: We introduce a new approach to deciding the number of clusters. The approach is applied to Optimally Tuned Robust Improper Maximum Likelihood Estimation (OTRIMLE; Coretto & Hennig, Journal of the American Statistical Association 111, 1648–1659) of a Gaussian mixture model allowing for observations to be classified as ‘noise’, but it can be applied to other clustering methods as well. The quality of a clustering is assessed by a statistic Q that measures how close the within‐cluster distributions are to elliptical unimodal distributions that have the only mode in the mean. This non‐parametric measure allows for non‐Gaussian clusters as long as they have a good quality according to Q. The simplicity of a model is assessed by a measure S that prefers a smaller number of clusters unless additional clusters can reduce the estimated noise proportion substantially. The simplest model is then chosen that is adequate for the data in the sense that its observed value of Q is not significantly larger than what is expected for data truly generated from the fitted model, as can be assessed by parametric bootstrap. The approach is compared with model‐based clustering using the Bayesian information criterion (BIC) and the integrated complete likelihood (ICL) in a simulation study and on two real data sets.

In this paper we study a finite Gaussian mixture model with an additional uniform component that has the role to catch points in the tails of the data distribution. An adaptive constraint enforces a certain level of separation between the Gaussian mixture components and the uniform component representing noise and outliers in the tail of the distribution. The latter makes the proposed tool particularly useful for robust estimation and outlier identification. A constrained ML estimator is introduced for which existence and consistency is shown. One of the attractive features of the methodology is that the noise level is estimated from data. We also develop an EM-type algorithm with proven convergence. Based on numerical evidence we show how the methods developed in this paper are useful for several fundamental data analysis tasks: outlier identification, robust location-scale estimation, clustering, and density estimation.