CheS-Mapper 2.0 for visual validation of (Q)SAR models

Abstract

BackgroundSound statistical validation is important to evaluate and compare the overall performance of (Q)SAR models. However, classical validation does not support the user in better understanding the properties of the model or the underlying data. Even though, a number of visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allow the investigation of model validation results are still lacking.ResultsWe propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. The approach applies the 3D viewer CheS-Mapper, an open-source application for the exploration of small molecules in virtual 3D space. The present work describes the new functionalities in CheS-Mapper 2.0, that facilitate the analysis of (Q)SAR information and allows the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. The approach is generic: It is model-independent and can handle physico-chemical and structural input features as well as quantitative and qualitative endpoints.ConclusionsVisual validation with CheS-Mapper enables analyzing (Q)SAR information in the data and indicates how this information is employed by the (Q)SAR model. It reveals, if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org.Graphical abstractComparing actual and predicted activity values with CheS-Mapper.

Open source molecular modeling

“…CheS-Mapper (chemical space mapper) [93, 84]. is a 3D-viewer for small compounds in chemical datasets.…”

Progress in visual representations of chemical space

“…CheS-Mapper [103,104] is a rare example of the software tool allowing the interaction with the chemical space in a 'real' 3D space instead of much more common 2D. Compounds are embedded into a rotatable 3D space, allowing the interaction with them and convenient analysis of various properties.…”

Scaffold Hunter: a comprehensive visual analytics framework for drug discovery

“…KNIME additionally integrates specific cheminformatics extensions [12]. Some of them focus on the integration of chemical toolkits (e.g., RDKit [13], CDK [14], and Indigo [15]) and some others on analytical aspects (e.g., CheS-Mapper [16, 17]). CDK is likewise available in Taverna [18, 19] and Pipeline Pilot can integrate ChemAxon components [20].…”

“…Recently, tools tailored to the specific needs of life scientists in the chemical biology, medicinal chemistry and pharmaceutical domain were developed. These include MONA 2 [21], Screening Assistant 2 [22], DataWarrior [23], the Chemical Space Mapper (CheS-Mapper) [16, 17] and the High-Throughput Screening Exploration Environment (HiTSEE) [24, 25]. The last two tools complement the workflow environment KNIME with a visualization node.…”