PubChem 2019 update: improved access to chemical data.
ABSTRACT: PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.
Project description:PubChem is a chemical data repository that provides comprehensive information on various chemical entities. It contains a wealth of chemical information from hundreds of data sources. Programmatic access to this large amount of data provides researchers with new opportunities for data-intensive research. PubChem provides several programmatic access routes. One of these is PUG-View, which is a Representational State Transfer (REST)-style web service interface specialized for accessing annotation data contained in PubChem. The present paper describes various aspects of PUG-View, including the scope of data accessible through PUG-View, the syntax for formulating a PUG-View request URL, the difference of PUG-View from other web service interfaces in PubChem, and its limitations and usage policies.
Project description:PubChem (https://pubchem.ncbi.nlm.nih.gov) is one of the largest open chemical information resources available. It currently receives millions of unique users per month on average, serving as a key resource for many research fields such as cheminformatics, chemical biology, medicinal chemistry, and drug discovery. PubChem provides multiple programmatic access routes to its data and services. One of them is PUG-REST, a Representational State Transfer (REST)-like web service interface to PubChem. On average, PUG-REST receives more than a million requests per day from tens of thousands of unique users. The present paper provides an update on PUG-REST since our previous paper published in 2015. This includes access to new kinds of data (e.g. concise bioactivity data, table of contents headings, etc.), full implementation of synchronous fast structure search, support for assay data retrieval using accession identifiers in response to the deprecation of NCBI's GI numbers, data exchange between PUG-REST and NCBI's E-Utilities through the List Gateway, implementation of dynamic traffic control through throttling, and enhanced usage policies. In addition, example Perl scripts are provided, which the user can easily modify, run, or translate into another scripting language.
Project description:PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, developed and maintained by the US National Institutes of Health (NIH). PubChem contains more than 180 million depositor-provided chemical substance descriptions, 60 million unique chemical structures and 225 million bioactivity assay results, covering more than 9000 unique protein target sequences. As an information resource for the chemical biology research community, it routinely receives more than 1 million requests per day from an estimated more than 1 million unique users per month. Programmatic access to this vast amount of data is provided by several different systems, including the US National Center for Biotechnology Information (NCBI)'s Entrez Utilities (E-Utilities or E-Utils) and the PubChem Power User Gateway (PUG)-a common gateway interface (CGI) that exchanges data through eXtended Markup Language (XML). Further simplifying programmatic access, PubChem provides two additional general purpose web services: PUG-SOAP, which uses the simple object access protocol (SOAP) and PUG-REST, which is a Representational State Transfer (REST)-style interface. These interfaces can be harnessed in combination to access the data contained in PubChem, which is integrated with the more than thirty databases available within the NCBI Entrez system.
Project description:PubChem's BioAssay database (https://pubchem.ncbi.nlm.nih.gov) has served as a public repository for small-molecule and RNAi screening data since 2004 providing open access of its data content to the community. PubChem accepts data submission from worldwide researchers at academia, industry and government agencies. PubChem also collaborates with other chemical biology database stakeholders with data exchange. With over a decade's development effort, it becomes an important information resource supporting drug discovery and chemical biology research. To facilitate data discovery, PubChem is integrated with all other databases at NCBI. In this work, we provide an update for the PubChem BioAssay database describing several recent development including added sources of research data, redesigned BioAssay record page, new BioAssay classification browser and new features in the Upload system facilitating data sharing.
Project description:PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Project description: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.
Project description:BACKGROUND:PubChem is an open repository for chemical structures, biological activities and biomedical annotations. Semantic Web technologies are emerging as an increasingly important approach to distribute and integrate scientific data. Exposing PubChem data to Semantic Web services may help enable automated data integration and management, as well as facilitate interoperable web applications. DESCRIPTION:This work, one of a series covering the PubChemRDF project, describes an approach to translate PubChem Substance and Compound information into Resource Description Framework (RDF) format. Basic examples are provided to demonstrate its use. The aim of this effort is to provide two new primary benefits to researchers in a cost-effective manner. Firstly, we aim to remove the inherent limitations of using the web-based resource PubChem by allowing a researcher to use readily available semantic technologies (namely, RDF triple stores and their corresponding SPARQL query engines) to query and analyze PubChem data on local computing resources. Secondly, this work intends to help improve data sharing, analysis, and integration of PubChem data to resources external to NCBI and across scientific domains, by means of the association of PubChem data to existing ontological frameworks, including CHEMical INFormation ontology, Semanticscience Integrated Ontology, and others. CONCLUSIONS:With the goal of semantically describing information available in the PubChem archive, pre-existing ontological frameworks were used, rather than creating new ones. Semantic relationships between compounds and substances, chemical descriptors associated with compounds and substances, interrelationships between chemicals, as well as provenance and attribute metadata of substances are described. Graphical abstract:Schematic representation of the semantic links for PubChem compounds and substances.
Project description:High-throughput screening (HTS) is now routinely conducted for drug discovery by both pharmaceutical companies and screening centers at academic institutions and universities. Rapid advance in assay development, robot automation, and computer technology has led to the generation of terabytes of data in screening laboratories. Despite the technology development toward HTS productivity, fewer efforts were devoted to HTS data integration and sharing. As a result, the huge amount of HTS data was rarely made available to the public. To fill this gap, the PubChem BioAssay database ( https://www.ncbi.nlm.nih.gov/pcassay/ ) was set up in 2004 to provide open access to the screening results tested on chemicals and RNAi reagents. With more than 10 years' development and contributions from the community, PubChem has now become the largest public repository for chemical structures and biological data, which provides an information platform to worldwide researchers supporting drug development, medicinal chemistry study, and chemical biology research. This work presents a review of the HTS data content in the PubChem BioAssay database and the progress of data deposition to stimulate knowledge discovery and data sharing. It also provides a description of the database's data standard and basic utilities facilitating information access and use for new users.
Project description:A bibliometric analysis of PubChem applications is presented by reviewing 1132 research articles. The massive volume of chemical structure and bioactivity data in PubChem and its online services have been used globally in various fields including chemical biology, medicinal chemistry and informatics research. PubChem supports drug discovery in many aspects such as lead identification and optimization, compound-target profiling, polypharmacology studies and unknown chemical identity elucidation. PubChem has also become a valuable resource for developing secondary databases, informatics tools and web services. The growing PubChem resource with its public availability offers support and great opportunities for the interrogation of pharmacological mechanisms and the genetic basis of diseases, which are vital for drug innovation and repurposing.
Project description:BACKGROUND:Developing structure-activity relationships (SARs) of molecules is an important approach in facilitating hit exploration in the early stage of drug discovery. Although information on millions of compounds and their bioactivities is freely available to the public, it is very challenging to infer a meaningful and novel SAR from that information. RESULTS:Research discussed in the present paper employed a bioactivity-centered clustering approach to group 843,845 non-inactive compounds stored in PubChem according to both structural similarity and bioactivity similarity, with the aim of mining bioactivity data in PubChem for useful SAR information. The compounds were clustered in three bioactivity similarity contexts: (1) non-inactive in a given bioassay, (2) non-inactive against a given protein, and (3) non-inactive against proteins involved in a given pathway. In each context, these small molecules were clustered according to their two-dimensional (2-D) and three-dimensional (3-D) structural similarities. The resulting 18 million clusters, named "PubChem SAR clusters", were delivered in such a way that each cluster contains a group of small molecules similar to each other in both structure and bioactivity. CONCLUSIONS:The PubChem SAR clusters, pre-computed using publicly available bioactivity information, make it possible to quickly navigate and narrow down the compounds of interest. Each SAR cluster can be a useful resource in developing a meaningful SAR or enable one to design or expand compound libraries from the cluster. It can also help to predict the potential therapeutic effects and pharmacological actions of less-known compounds from those of well-known compounds (i.e., drugs) in the same cluster.