The 24th annual Nucleic Acids Research database issue: a look back and upcoming changes.

This year's Database Issue of Nucleic Acids Research contains 152 papers that include descriptions of 54 new databases and update papers on 98 databases, of which 16 have not been previously featured in NAR As always, these databases cover a broad range of molecular biology subjects, including genome structure, gene expression and its regulation, proteins, protein domains, and protein-protein interactions. Following the recent trend, an increasing number of new and established databases deal with the issues of human health, from cancer-causing mutations to drugs and drug targets. In accordance with this trend, three recently compiled databases that have been selected by NAR reviewers and editors as 'breakthrough' contributions, denovo-db, the Monarch Initiative, and Open Targets, cover human de novo gene variants, disease-related phenotypes in model organisms, and a bioinformatics platform for therapeutic target identification and validation, respectively. We expect these databases to attract the attention of numerous researchers working in various areas of genetics and genomics. Looking back at the past 12 years, we present here the 'golden set' of databases that have consistently served as authoritative, comprehensive, and convenient data resources widely used by the entire community and offer some lessons on what makes a successful database. The Database Issue is freely available online at the https://academic.oup.com/nar web site. An updated version of the NAR Molecular Biology Database Collection is available at http://www.oxfordjournals.org/nar/database/a/.

[The French National Compound Library: advances and future prospects]. / Chimiothèque Nationale - Avancées et perspectives.

The French National Compound Library (Chimiothèque Nationale) has been created in 2003 and is the federation of local collections. It contains more than 56 000 small molecules and natural compounds synthesised or isolated in different laboratories over the past years. This explains the diversity of the collection. The strength of this initiative is the ability to connect chemists and biologists for the development of hits. This development involves the synthesis of analogues or/and chemical tools to find new targets. These collaborations lead to the identification of new chemical probes. These probes able to modulate a biological function are essential to study biological pathways. They can also be useful for therapeutic applications. This article will describe the major achievements and perspectives of the French Chemical Library.

The Evolution of Digital Chemistry at Southampton.

In this paper we take a historical view of e-Science and e-Research developments within the Chemical Sciences at the University of Southampton, showing the development of several stages of the evolving data ecosystem as Chemistry moves into the digital age of the 21(st) Century. We cover our research on aspects of the representation of chemical information in the context of the world wide web (WWW) and its semantic enhancement (the Semantic Web) and illustrate this with the example of the representation of quantities and units within the Semantic Web. We explore the changing nature of laboratories as computing power becomes increasing powerful and pervasive and specifically look at the function and role of electronic or digital notebooks. Having focussed on the creation of chemical data and information in context, we finish the paper by following the use and reuse of this data as facilitated by the features provided by digital repositories and their importance in facilitating the exchange of chemical information touching on the issues of open and or intelligent access to the data.

Incorporating new technologies into toxicity testing and risk assessment: moving from 21st century vision to a data-driven framework.

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency.

Towards a gold standard: regarding quality in public domain chemistry databases and approaches to improving the situation.

In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to ensure that the data are high quality to ensure that time is not wasted in erroneous searches, that models are underpinned by accurate data and that improved discoverability of online resources is not marred by incorrect data. In this article we provide an overview of some of the experiences of the authors using online chemical compound databases, critique the approaches taken to assemble data and we suggest approaches to deliver definitive reference data sources.