Interoperable chemical structure search service

Abstract

Motivation The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search across multiple databases provides a way to efficiently utilize these resources. To simplify such searches, many databases have adopted semantic technologies that allow interoperable querying of the datasets using SPARQL query language. However, the interoperable interfaces of the chemical databases still lack the functionality of structure-driven chemical search, which is a fundamental method of data discovery in the chemical search space. Results We present a SPARQL service that augments existing semantic services by making interoperable substructure and similarity searches in small-molecule databases possible. The service thus offers new possibilities for querying interoperable databases, and simplifies writing of heterogeneous queries that include chemical-structure search terms. Availability The service is freely available and accessible using a standard SPARQL endpoint interface. The service documentation and user-oriented demonstration interfaces that allow quick explorative querying of datasets are available at https://idsm.elixir-czech.cz.

Diverse Taxonomies for Diverse Chemistries: Enhanced Representation of Natural Product Metabolism in UniProtKB

“…The query shown in Figure S7 will retrieve all enzymes annotated in UniProtKB/Swiss-Prot that metabolize compounds similar to patulin—but not necessarily identical to patulin. The query uses the SMILES representation (Simplified Molecular-Input Line-Entry System) (opensmiles.org) of patulin, as required for structure searches by IDSM, and uses the sachem:similaritySearch procedure call pattern developed by the IDSM team [ 33 ] with a similarity score threshold of 0.8 (the similarity score is based on Jaccard similarity of Morgan-style connectivity fingerprints). The query is designed with two nested services (“calls”) as illustrated in Figure 5 .…”

The LOTUS Initiative for Open Natural Products Research: Knowledge Management through Wikidata

“…(Kratochvíl et al, 2018). The engine is used by the Integrated Database of Small Molecules (IDSM) that operates, among other things, several dedicated endpoints allowing structural search in selected small-molecule datasets via SPARQL (Kratochvíl et al, 2019). To allow substructure and similarity searches via SPARQL also on compounds from WD, we created a dedicated IDSM/Sachem endpoint for WD as well.…”

“…To address this issue, Galgonek et al developed an in-house SPARQL engine that allows utilization of Sachem, a high-performance chemical DB cartridge for PostgreSQL for fingerprint-guided substructure and similarity search (Kratochvíl et al, 2018). The engine is used by the Integrated Database of Small Molecules (IDSM) that operates, among other things, several dedicated endpoints allowing structural search in selected small-molecule datasets via SPARQL (Kratochvíl et al, 2019). To allow substructure and similarity searches via SPARQL also on compounds from Wikidata, a dedicated IDSM/Sachem endpoint was created for the LOTUS project.…”

Enzyme annotation in UniProtKB using Rhea

“…The query shown in Figure 3 makes use of the ChEBI ontology to find information relevant to cholesterol and other sterols. Users might also identify derivatives of cholesterol or cholesterol like molecules using SPARQL endpoints that support chemical similarity or chemical substructure searches over ChEBI, such as the Integrated Database of Small Molecules (IDSM) (Kratochvil et al, 2019). These advanced search capabilities could be further combined with those of a range of other SPARQL endpoints from resources such as Ensembl (Zerbino et al, 2018), OMA (Altenhoff et al, 2018), OrthoDB (Kriventseva et al, 2019) and Bgee (Bastian et al, 2008), in order to explore small molecule metabolism in the context of genomic organization, variation, evolution and anatomy.…”