The ChEMBL database in 2017 Gaulton, Anna; Hersey, Anne; Nowotka, Michał ...
Nucleic acids research,
01/2017, Letnik:
45, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 and 2014 Nucleic Acids Research Database Issues. Since then, alongside the ...continued extraction of data from the medicinal chemistry literature, new sources of bioactivity data have also been added to the database. These include: deposited data sets from neglected disease screening; crop protection data; drug metabolism and disposition data and bioactivity data from patents. A number of improvements and new features have also been incorporated. These include the annotation of assays and targets using ontologies, the inclusion of targets and indications for clinical candidates, addition of metabolic pathways for drugs and calculation of structural alerts. The ChEMBL data can be accessed via a web-interface, RDF distribution, data downloads and RESTful web-services.
A comprehensive map of molecular drug targets Santos, Rita; Ursu, Oleg; Gaulton, Anna ...
Nature reviews. Drug discover/Nature reviews. Drug discovery,
01/2017, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, ...understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development. Here, we present an updated comprehensive map of molecular targets of approved drugs. We curate a total of 893 human and pathogen-derived biomolecules through which 1,578 US FDA-approved drugs act. These biomolecules include 667 human-genome-derived proteins targeted by drugs for human disease. Analysis of these drug targets indicates the continued dominance of privileged target families across disease areas, but also the growth of novel first-in-class mechanisms, particularly in oncology. We explore the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes. Through the collaboration of three independent teams, we highlight some of the ongoing challenges in accurately defining the targets of molecular therapeutics and present conventions for deconvoluting the complexities of molecular pharmacology and drug efficacy.
Abstract
ChEMBL is a large, open-access bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012, 2014 and 2017 Nucleic Acids Research Database Issues. In the last two ...years, several important improvements have been made to the database and are described here. These include more robust capture and representation of assay details; a new data deposition system, allowing updating of data sets and deposition of supplementary data; and a completely redesigned web interface, with enhanced search and filtering capabilities.
Over the last decades, the different issues regarding the expansion of the wildland-urban interface (WUI) - particularly those related to fires - have spread around the world with particular exposure ...in the USA, Canada, Australia, and, more recently, in southern European countries (e.g. Portugal and Greece). It has been receiving even more attention from the scientific community particularly due to the ecological and sociological implications on the management of natural resources and decisions associated with spatial planning.
Consequently, throughout the extensive research conducted on wildfires, there has been a growing interest and body of literature on wildfires in the WUI worldwide. Although there are many articles published in English, in indexed journals, there is an excellent body of literature published in other languages (e.g. French, Spanish, Portuguese), which is not very well known and rarely cited.
In this body of literature, whether in English or other languages, concepts and definitions are not always consensual. In this sense, this paper aims at reviewing the key concepts regarding intrinsic characteristics of the WUI and wildfires in the WUI, presenting evaluation methodologies that have been applied to WUI and analyzing several risk prevention and reduction programs developed in WUI affected by forest fires in different parts of the world. Through our analysis we found that the work developed by researchers worldwide on this subject is significant, considering the increasing relevance of this environmental problem. However, it is fundamental to define standardized methodologies in order to facilitate the transfer of knowledge and promote cooperation, interdisciplinarity. The implementation of a collaborative approach is needed, especially in the development of strategies to prevent and reduce fire risk in these areas.
Display omitted
•Fire in the WUI has been increasing significantly over the last decades.•There has been an exponential growth of the scientific production on WUI.•There are different WUI evaluation methodologies that must be standardized.•Interdisciplinary approach is necessary to understand the complexity of WUI.
Background
The ChEMBL database is one of a number of public databases that contain bioactivity data on small molecule compounds curated from diverse sources. Incoming compounds are typically not ...standardised according to consistent rules. In order to maintain the quality of the final database and to easily compare and integrate data on the same compound from different sources it is necessary for the chemical structures in the database to be appropriately standardised.
Results
A chemical curation pipeline has been developed using the open source toolkit RDKit. It comprises three components: a
Checker
to test the validity of chemical structures and flag any serious errors; a
Standardizer
which formats compounds according to defined rules and conventions and a
GetParent
component that removes any salts and solvents from the compound to create its parent. This pipeline has been applied to the latest version of the ChEMBL database as well as uncurated datasets from other sources to test the robustness of the process and to identify common issues in database molecular structures.
Conclusion
All the components of the structure pipeline have been made freely available for other researchers to use and adapt for their own use. The code is available in a GitHub repository and it can also be accessed via the ChEMBL Beaker webservices. It has been used successfully to standardise the nearly 2 million compounds in the ChEMBL database and the compound validity checker has been used to identify compounds with the most serious issues so that they can be prioritised for manual curation.
ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published ...literature on a regular basis, then further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 5.4 million bioactivity measurements for more than 1 million compounds and 5200 protein targets. Access is available through a web-based interface, data downloads and web services at: https://www.ebi.ac.uk/chembldb.
The ChEMBL bioactivity database: an update Bento, A Patrícia; Gaulton, Anna; Hersey, Anne ...
Nucleic acids research,
01/2014, Letnik:
42, Številka:
Database issue
Journal Article
Recenzirano
Odprti dostop
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources ...and improvements in functionality have contributed to the growth and utility of the resource. In particular, more comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications; a new richer data model for representing drug targets has been developed; and a number of methods have been put in place to allow users to more easily identify reliable data. Finally, access to ChEMBL is now available via a new Resource Description Framework format, in addition to the web-based interface, data downloads and web services.
The safety of marketed drugs is an ongoing concern, with some of the more frequently prescribed medicines resulting in serious or life-threatening adverse effects in some patients. Safety-related ...information for approved drugs has been curated to include the assignment of toxicity class(es) based on their withdrawn status and/or black box warning information described on medicinal product labels. The ChEMBL resource contains a wide range of bioactivity data types, from early “Discovery” stage preclinical data for individual compounds through to postclinical data on marketed drugs; the inclusion of the curated drug safety data set within this framework can support a wide range of safety-related drug discovery questions. The curated drug safety data set will be made freely available through ChEMBL and updated in future database releases.
Climate change has exacerbated the frequency and severity of droughts worldwide. Evaluating the response of gross primary productivity (GPP) to drought is thus beneficial to improving our ...understanding of the impact of drought on the carbon cycle balance. Although many studies have investigated the relationship between vegetation productivity and dry/wet conditions, the capability of different drought indices of assessing the influence of water deficit is not well understood. Moreover, few studies consider the effects of drought on vegetation with a focus on periods of drought. Here, we investigated the spatial-temporal patterns of GPP, the standardized precipitation evapotranspiration index (SPEI), and the vapor pressure deficit (VPD) in China from 2001 to 2020 and examined the relationship between GPP and water deficit/drought for different vegetation types. The results revealed that SPEI and GPP were positively correlated over approximately 70.7% of the total area, and VPD was negatively correlated with GPP over about 66.2% of the domain. Furthermore, vegetation productivity was more negatively affected by water deficit in summer and autumn. During periods of drought, the greatest negative impact was on deciduous forests and croplands, and woody savannas were the least impacted. This research provides a scientific reference for developing mitigation and adaptation measures to lessen the impact of drought disasters under a changing climate.
This paper develops a methodology to determine the economic feasibility of implementing offshore wave energy farms on the Portuguese continental coast. This methodology follows several phases: the ...geographic phase, the energy phase, the economic phase, and the restrictions phase. First, in the geographic phase, the height and the period of the waves, the bathymetry, the distance from the farm to the shore, from farm to shipyard, and from farm to port, are calculated. In the energy phase the energy produced by each wave energy converter is determined, and in the economic phase, the parameters calculated in the previous phases are used as input to find the economic parameters. Finally, in the restrictions phase, a limitation by the bathymetry will be added to the economic maps, whose value will be different depending on the floating offshore wave energy converter (WEC). In this study, three wave energy converters have been considered, Pelamis, AquaBuOY, and Wave Dragon, and several scenarios for electric tariffs have been taken into account. The results obtained indicate what the best WEC is for this study in terms of its levelized cost of energy (LCOE), internal rate of return (IRR), and net present value (NPV), and where the best area is to install wave energy farms.
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