Cluster Optimized Proximity Scaling

Multidimensional scaling (MDS) methods that aim at pronouncing the clustered appearance of the configuration (Rusch, Mair & Hornik, 2021, ). They achieve this by transforming proximities/distances with explicit power functions and penalizing the fitting criterion with a clusteredness index, the OPTICS Cordillera (Rusch, Hornik & Mair, 2018, ). There are two variants: One for finding the configuration directly (COPS-C) with given explicit power transformations and implicit ratio, interval and non-metric optimal scaling transformations (Borg & Groenen, 2005, ISBN:978-0-387-28981-6), and one for using the augmented fitting criterion to find optimal hyperparameters for the explicit transformations (P-COPS). The package contains various functions, wrappers, methods and classes for fitting, plotting and displaying a large number of different MDS models (most of the functionality in smacofx) in the COPS framework. The package further contains a function for pattern search optimization, the ``Adaptive Luus-Jaakola Algorithm'' (Rusch, Mair & Hornik, 2021,) and a functions to calculate the phi-distances for count data or histograms.

High-Throughput Toxicokinetics

Pre-made models that can be rapidly tailored to various chemicals and species using chemical-specific in vitro data and physiological information. These tools allow incorporation of chemical toxicokinetics ("TK") and in vitro-in vivo extrapolation ("IVIVE") into bioinformatics, as described by Pearce et al. (2017) (). Chemical-specific in vitro data characterizing toxicokinetics have been obtained from relatively high-throughput experiments. The chemical-independent ("generic") physiologically-based ("PBTK") and empirical (for example, one compartment) "TK" models included here can be parameterized with in vitro data or in silico predictions which are provided for thousands of chemicals, multiple exposure routes, and various species. High throughput toxicokinetics ("HTTK") is the combination of in vitro data and generic models. We establish the expected accuracy of HTTK for chemicals without in vivo data through statistical evaluation of HTTK predictions for chemicals where in vivo data do exist. The models are systems of ordinary differential equations that are developed in MCSim and solved using compiled (C-based) code for speed. A Monte Carlo sampler is included for simulating human biological variability (Ring et al., 2017 ) and propagating parameter uncertainty (Wambaugh et al., 2019 ). Empirically calibrated methods are included for predicting tissue:plasma partition coefficients and volume of distribution (Pearce et al., 2017 ). These functions and data provide a set of tools for using IVIVE to convert concentrations from high-throughput screening experiments (for example, Tox21, ToxCast) to real-world exposures via reverse dosimetry (also known as "RTK") (Wetmore et al., 2015 ).