Toward the Replacement of Animal Experiments through the Bioinformatics-driven Analysis of ‘Omics’ Data from Human Cell Cultures

Roland C. Grafström, Penny Nymark, Vesa Hongisto, Ola Spjuth, Rebecca Ceder, Egon Willighagen, Barry Hardy, Samuel Kaski and Pekka Kohonen

This paper outlines the work for which Roland Grafström and Pekka Kohonen were awarded the 2014 Lush Science Prize. The research activities of the Grafström laboratory have, for many years, covered cancer biology studies, as well as the development and application of toxicity-predictive in vitro models to determine chemical safety. Through the integration of in silico analyses of diverse types of genomics data (transcriptomic and proteomic), their efforts have proved to fit well into the recently-developed Adverse Outcome Pathway paradigm. Genomics analysis within state-of-the-art cancer biology research and Toxicology in the 21st Century concepts share many technological tools. A key category within the Three Rs paradigm is the Replacement of animals in toxicity testing with alternative methods, such as bioinformatics-driven analyses of data obtained from human cell cultures exposed to diverse toxicants. This work was recently expanded within the pan-European SEURAT-1 project (Safety Evaluation Ultimately Replacing Animal Testing), to replace repeat-dose toxicity testing with data-rich analyses of sophisticated cell culture models. The aims and objectives of the SEURAT project have been to guide the application, analysis, interpretation and storage of ‘omics’ technology-derived data within the service-oriented sub-project, ToxBank. Particularly addressing the Lush Science Prize focus on the relevance of toxicity pathways, a ‘data warehouse’ that is under continuous expansion, coupled with the development of novel data storage and management methods for toxicology, serve to address data integration across multiple ‘omics’ technologies. The prize winners’ guiding principles and concepts for modern knowledge management of toxicological data are summarised. The translation of basic discovery results ranged from chemical-testing and material testing data, to information relevant to human health and environmental safety.
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Co-occurring Words: Finding Information About Alternatives to Animal Testing

Jane Huggins

A collection of co-occurring words has been gathered from a small database of abstracts about alternatives to skin irritation testing by using Boolean logic. Words were selected according to a strategy based on methodology. Such words and their co-occurrences may be considered an archival code by which data that describe alternatives to skin irritation testing can be more readily recognised. As such, they can be used to enhance the efficiency with which information about this area of alternatives to animal testing is found in journal articles, databases and Web sites
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he ECVAM Scientific Information Service (SIS)

Annett Janusch Roi

The aim of this ECVAM Status Seminar was to critically review the contributions made by ECVAM in relation to its four main tasks. The establishment and maintenance of the ECVAM Scientific Information Service (SIS) is a precise means of fulfilling one of these four principal duties of ECVAM. The major achievements of the SIS, and the efforts required to achieve them, are discussed, together with the immediate future for the SIS.
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Information: Needs for the Future

Krys Bottrill

The four central questions surrounding the use of information are: where to find it; how to find it; how to present it; and how to maintain information availability and information literacy. It is usually assumed that the main source of information for most scientists is the peer-reviewed journal literature. Traditional journal publishing is beset with a number of problems. Although electronic publishing might possibly solve some of these, it in turn introduces new problems. Further problems arise with respect to secondary sources which, in some cases, are being supplemented by electronic archives of full-text documents. One fundamental question that arises when considering any large collection of documents or of records about documents is whether or not to index them, and how to index them. The pros and cons of free-text searching versus the use of controlled vocabularies are discussed, as is the importance of harmonising the Three Rs-related terminology of existing and proposed thesauri. However, there is a further problem that documents pertinent to the Three Rs are not always indexed from this point of view. Authors need to be made aware that, if the information is not provided in the abstract, there is no easy way to identify and retrieve this document from a database. Small specialised databases on the Three Rs in relation to specific subject areas could provide a further solution, especially if they provided references to conference proceedings and book chapters, which are not usually found in the large bibliographical databases. The provision of training in the use of information resources, and the establishment and maintenance of these resources, require investment of money and professional skills. Finally, the future of Three Rs information depends on a recognition that this in an important topic which deserves more than lip service.
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Assessing the Search for and Implementation of the Three Rs: A Survey among Scientists

Marlies Leenaars, Bart Savenije, Anne Nagtegaal, Lilian van der Vaart and Merel Ritskes-Hoitinga

A survey among scientists into the current practice of searching for Replacement, Reduction and Refinement (Three Rs) alternatives, highlights the gap between the statutory required need to apply the Three Rs concept whenever possible and the lack of criteria for searching for Three Rs alternatives. A questionnaire was distributed to 342 scientists (Federation of European Laboratory Animal Science Associations [FELASA] Category C and B individuals), of which 67 responded. These scientists are customers of the Central Animal Laboratory of Radboud University Nijmegen Medical Centre. The results indicate that there is room for improvement in searching effectively for the Three Rs: skills in searching biomedical databases for Three Rs alternatives are limited, knowledge of specialised Three Rs databases is very limited, and satisfaction on the availability and accessibility of Three Rs information is low. None of the respondents allocate budget for a specific Three Rs alternatives search, although 50% do spend, on average, two hours engaged in this search for each application to their animal ethics committees. The majority of the respondents expressed the wish that the search for alternatives could be easier and less time consuming, and prefer to achieve this through the service offered by specialists at the Central Animal Laboratory. On the basis of the results from the questionnaire, the 3R Research Centre was established, with the aim of providing services and support for biomedical scientists, to improve the search for, and subsequent implementation of, the Three Rs.
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