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PubChem chemical structure standardization.

ABSTRACT: BACKGROUND:PubChem is a chemical information repository, consisting of three primary databases: Substance, Compound, and BioAssay. When individual data contributors submit chemical substance descriptions to Substance, the unique chemical structures are extracted and stored into Compound through an automated process called structure standardization. The present study describes the PubChem standardization approaches and analyzes them for their success rates, reasons that cause structures to be rejected, and modifications applied to structures during the standardization process. Furthermore, the PubChem standardization is compared to the structure normalization of the IUPAC International Chemical Identifier (InChI) software, as manifested by conversion of the InChI back into a chemical structure. RESULTS:The observed rejection rate for substances processed by PubChem standardization was 0.36%, which is predominantly attributed to structures with invalid atom valences that cannot be readily corrected without additional information from contributors. Of all structures that pass standardization, 44% are modified in the process, reducing the count of unique structures from 53,574,724 in substance to 45,808,881 in compound as identified by de-aromatized canonical isomeric SMILES. Even though the processing time is very low on average (only 0.4% of structures have individual standardization time above 0.1 s), total standardization time is completely dominated by edge cases: 90% of the time to standardize all structures in PubChem substance is spent on the 2.05% of structures with the highest individual standardization time. It is worth noting that 60% of the structures obtained from PubChem structure standardization are not identical to the chemical structure resulting from the InChI (primarily due to preferences for a different tautomeric form). CONCLUSIONS:Standardization of chemical structures is complicated by the diversity of chemical information and their representations approaches. The PubChem standardization is an effective and efficient tool to account for molecular diversity and to eliminate invalid/incomplete structures. Further development will concentrate on improved tautomer consideration and an expanded stereocenter definition. Modifications are difficult to thoroughly validate, with slight changes often affecting many thousands of structures and various edge cases. The PubChem structure standardization service is accessible as a public resource ( https://pubchem.ncbi.nlm.nih.gov/standardize ), and via programmatic interfaces.

SUBMITTER: Hahnke VD

PROVIDER: S-EPMC6086778 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Project description:PubChem (https://pubchem.ncbi.nlm.nih.gov) is a public chemical database that serves scientific communities as well as the general public. This database collects chemical information from hundreds of data sources and organizes them into multiple data collections, including Substance, Compound, BioAssay, Protein, Gene, Pathway, and Patent. These collections are interlinked with each other, allowing users to discover related records in the various collections (e.g., drugs targeting a protein or genes modulated by a chemical). PubChem can be searched by keyword (e.g., a chemical, protein, or gene name) as well as by chemical structure. The input structure can be provided using popular line notations or drawn with the PubChem Sketcher. PubChem supports various types of structure searches, including identity search, 2-D and 3-D similarity searches, and substructure and superstructure searches. Results from multiple searches can be combined using Boolean operators (i.e., AND, OR, and NOT) to formulate complex queries. PubChem allows the user to quickly retrieve a list of records annotated with a particular classification or ontological term. This paper provides step-by-step instructions on how to explore PubChem data with examples of commonly requested tasks. © 2021. This article is a U.S. Government work and is in the public domain in the USA. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Finding genes and proteins that interact with a given compound Basic Protocol 2: Finding drug-like compounds similar to a query compound through a two-dimensional (2-D) similarity search Basic Protocol 3: Finding compounds similar to a query compound through a three-dimensional (3-D) similarity search Support Protocol: Computing similarity scores between compounds Basic Protocol 4: Getting the bioactivity data for the hit compounds from substructure search Basic Protocol 5: Finding drugs that target a particular gene Basic Protocol 6: Getting bioactivity data of all chemicals tested against a protein. Basic Protocol 7: Finding compounds annotated with classifications or ontological terms Basic Protocol 8: Finding stereoisomers and isotopomers of a compound through identity search.

Project description:BackgroundThere 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.ResultsThe 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/.ConclusionA 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.

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PubChem chemical structure standardization.

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