Paul A. Thiessen

Bio: Paul A. Thiessen is an academic researcher from National Institutes of Health. The author has contributed to research in topics: PubChem & Conserved Domain Database. The author has an hindex of 3, co-authored 4 publications receiving 2519 citations.

PubChem Substance and Compound databases

Abstract: PubChem (https://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, launched in 2004 as a component of the Molecular Libraries Roadmap Initiatives of the US National Institutes of Health (NIH). For the past 11 years, PubChem has grown to a sizable system, serving as a chemical information resource for the scientific research community. PubChem consists of three inter-linked databases, Substance, Compound and BioAssay. The Substance database contains chemical information deposited by individual data contributors to PubChem, and the Compound database stores unique chemical structures extracted from the Substance database. Biological activity data of chemical substances tested in assay experiments are contained in the BioAssay database. This paper provides an overview of the PubChem Substance and Compound databases, including data sources and contents, data organization, data submission using PubChem Upload, chemical structure standardization, web-based interfaces for textual and non-textual searches, and programmatic access. It also gives a brief description of PubChem3D, a resource derived from theoretical three-dimensional structures of compounds in PubChem, as well as PubChemRDF, Resource Description Framework (RDF)-formatted PubChem data for data sharing, analysis and integration with information contained in other databases.

PUG-SOAP and PUG-REST: web services for programmatic access to chemical information in PubChem

Abstract: 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.

A structure-based method for protein sequence alignment

Abstract: Motivation: With the continuing rapid growth of protein sequence data, protein sequence comparison methods have become the most widely used tools of bioinformatics. Among these methods are those that use position-specific scoring matrices (PSSMs) to describe protein families. PSSMs can capture information about conserved patterns within families, which can be used to increase the sensitivity of searches for related sequences. Certain types of structural information, however, are not generally captured by PSSM search methods. Here we introduce a program, Structure-based ALignment TOol (SALTO), that aligns protein query sequences to PSSMs using rules for placing and scoring gaps that are consistent with the conserved regions of domain alignments from NCBI's Conserved Domain Database. Results: In most cases, the alignment scores obtained using the local alignment version follow an extreme value distribution. SALTO's performance in finding related sequences and producing accurate alignments is similar to or better than that of IMPALA; one advantage of SALTO is that it imposes an explicit gapping model on each protein family. Availability: A stand-alone version of the program that can generate global or local alignments is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/SALTO/), and has been incorporated to Cn3D structure/alignment viewer. Contact: bryant@ncbi.nlm.nih.gov

Bridging Chemical and Biological Information: Public Knowledge Spaces

Abstract: At the time of this writing, PubChem1 is probably the most widely known publicly accessible chemical compound database on the World Wide Web (WWW, or just Web). It contains not only chemical structures, but also biological data linked to these structures. PubChem was launched in 2004, but it is certainly not the first freely available, Web-accessible database providing biological information on the Internet. The biological data landscape is complicated by varying definitions of what classes of information should be considered as biological information. Do toxicity data constitute biological information? If yes, should a qualifying database contain actual measurements, or can this information be provided in distilled, abstracted formats, perhaps even as material safety data sheets (MSDSs) or simple handling classifiers? Do we simply

SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Abstract: To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

PubChem Substance and Compound databases

Abstract: PubChem (https://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, launched in 2004 as a component of the Molecular Libraries Roadmap Initiatives of the US National Institutes of Health (NIH). For the past 11 years, PubChem has grown to a sizable system, serving as a chemical information resource for the scientific research community. PubChem consists of three inter-linked databases, Substance, Compound and BioAssay. The Substance database contains chemical information deposited by individual data contributors to PubChem, and the Compound database stores unique chemical structures extracted from the Substance database. Biological activity data of chemical substances tested in assay experiments are contained in the BioAssay database. This paper provides an overview of the PubChem Substance and Compound databases, including data sources and contents, data organization, data submission using PubChem Upload, chemical structure standardization, web-based interfaces for textual and non-textual searches, and programmatic access. It also gives a brief description of PubChem3D, a resource derived from theoretical three-dimensional structures of compounds in PubChem, as well as PubChemRDF, Resource Description Framework (RDF)-formatted PubChem data for data sharing, analysis and integration with information contained in other databases.

MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis.

Abstract: We present a new update to MetaboAnalyst (version 4.0) for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since the last major update in 2015, MetaboAnalyst has continued to evolve based on user feedback and technological advancements in the field. For this year's update, four new key features have been added to MetaboAnalyst 4.0, including: (1) real-time R command tracking and display coupled with the release of a companion MetaboAnalystR package; (2) a MS Peaks to Pathways module for prediction of pathway activity from untargeted mass spectral data using the mummichog algorithm; (3) a Biomarker Meta-analysis module for robust biomarker identification through the combination of multiple metabolomic datasets and (4) a Network Explorer module for integrative analysis of metabolomics, metagenomics, and/or transcriptomics data. The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions. The underlying knowledgebases (compound libraries, metabolite sets, and metabolic pathways) have also been updated based on the latest data from the Human Metabolome Database (HMDB). A Docker image of MetaboAnalyst is also available to facilitate download and local installation of MetaboAnalyst. MetaboAnalyst 4.0 is freely available at http://metaboanalyst.ca.

HMDB 4.0: the human metabolome database for 2018.

Abstract: The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB's chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC-MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

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.