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The rapid increase of publicly available chemical structures and associated experimental data presents a valuable opportunity to build robust QSAR models for applications in different fields. However, the common concern is the quality of both the chemical structure information and associated experimental data. This is especially true when those data are collected from multiple sources as chemical substance mappings can contain many duplicate structures and molecular inconsistencies. Such issues can impact the resulting molecular descriptors and their mappings to experimental data and, subsequently, the quality of the derived models in terms of accuracy, repeatability, and reliability. Herein we describe the development of an automated workflow to standardize chemical structures according to a set of standard rules and generate two and/or three-dimensional "QSAR-ready" forms prior to the calculation of molecular descriptors. The workflow was designed in the KNIME workflow environment and consists of three high-level steps. First, a structure encoding is read, and then the resulting in-memory representation is cross-referenced with any existing identifiers for consistency. Finally, the structure is standardized using a series of operations including desalting, stripping of stereochemistry (for two-dimensional structures), standardization of tautomers and nitro groups, valence correction, neutralization when possible, and then removal of duplicates. This workflow was initially developed to support collaborative modeling QSAR projects to ensure consistency of the results from the different participants. It was then updated and generalized for other modeling applications. This included modification of the "QSAR-ready" workflow to generate "MS-ready structures" to support the generation of substance mappings and searches for software applications related to non-targeted analysis mass spectrometry. Both QSAR and MS-ready workflows are freely available in KNIME, via standalone versions on GitHub, and as docker container resources for the scientific community. Scientific contribution: This work pioneers an automated workflow in KNIME, systematically standardizing chemical structures to ensure their readiness for QSAR modeling and broader scientific applications. By addressing data quality concerns through desalting, stereochemistry stripping, and normalization, it optimizes molecular descriptors' accuracy and reliability. The freely available resources in KNIME, GitHub, and docker containers democratize access, benefiting collaborative research and advancing diverse modeling endeavors in chemistry and mass spectrometry. [ABSTRACT FROM AUTHOR] more...

Background: There are presently hundreds of online databases hosting millions of chemical compounds and associated data. As a result of the number of cheminformatics software tools that can be used to produce the data, subtle differences between the various cheminformatics platforms, as well as the naivety of the software users, there are a myriad of issues that can exist with chemical structure representations online. In order to help facilitate validation and standardization of chemical structure datasets from various sources we have delivered a freely available internet-based platform to the community for the processing of chemical compound datasets. Results: The chemical validation and standardization platform (CVSP) both validates and standardizes chemical structure representations according to sets of systematic rules. The chemical validation algorithms detect issues with submitted molecular representations using pre-defined or user-defined dictionary-based molecular patterns that are chemically suspicious or potentially requiring manual review. Each identified issue is assigned one of three levels of severity - Information, Warning, and Error - in order to conveniently inform the user of the need to browse and review subsets of their data. The validation process includes validation of atoms and bonds (e.g., making aware of query atoms and bonds), valences, and stereo. The standard form of submission of collections of data, the SDF file, allows the user to map the data fields to predefined CVSP fields for the purpose of cross-validating associated SMILES and InChIs with the connection tables contained within the SDF file. This platform has been applied to the analysis of a large number of data sets prepared for deposition to our ChemSpider database and in preparation of data for the Open PHACTS project. In this work we review the results of the automated validation of the DrugBank dataset, a popular drug and drug target database utilized by the community, and ChEMBL 17 data set. CVSP web site is located at http://cvsp.chemspider.com/. Conclusion: A platform for the validation and standardization of chemical structure representations of various formats has been developed and made available to the community to assist and encourage the processing of chemical structure files to produce more homogeneous compound representations for exchange and interchange between online databases. While the CVSP platform is designed with flexibility inherent to the rules that can be used for processing the data we have produced a recommended rule set based on our own experiences with the large data sets such as DrugBank, ChEMBL, and data sets from ChemSpider. [ABSTRACT FROM AUTHOR] more...