Highly Versatile Cloud-Based Automation Solution for the Remote Design and Execution of Experiment Protocols during the COVID-19 Pandemic.

There is an urgent need to accelerate the development and validation of both diagnostics and vaccines for COVID-19. These priorities are challenging both public and private sector research groups around the world and have shone a spotlight on both existing bottlenecks in the research workflows involved as well as on the implications of having to do much of this work remotely because of enforced social distancing and lockdown measures. The ability to respond quickly to rapidly evolving events, coupled with an emerging understanding of the disease and its pathology, as well as different mutations of the virus, necessitates a highly flexible liquid-handling automation solution that is amenable to rapid switching between different assay workflows and processes to be exploited tactically as needed. In addition, the use of cloud-based software imparts a unique benefit in enabling multiple research groups and remote technical staff around the world to have ready access to the same protocols in real-time without delays, down to the required level of detail, sharing methods and data (for example, in faster clinical trials). Informed by a recent use case, this article explores these issues alongside the recent development and deployment of an automation solution, whose unique approach in terms of both its cloud-native software and its highly modular hardware aligns especially well with achieving the challenge set by this new frontier in the bioanalytical laboratory.

3D-DIP-Chip: a microarray-based method to measure genomic DNA damage.

Genotoxins cause DNA damage, which can result in genomic instability. The genetic changes induced have far-reaching consequences, often leading to diseases such as cancer. A wide range of genotoxins exists, including radiations and chemicals found naturally in the environment, and in man-made forms created by human activity across a variety of industries. Genomic technologies offer the possibility of unravelling the mechanisms of genotoxicity, including the repair of genetic damage, enhancing our ability to develop, test and safely use existing and novel materials. We have developed 3D-DIP-Chip, a microarray-based method to measure the prevalence of genomic genotoxin-induced DNA damage. We demonstrate the measurement of both physical and chemical induced DNA damage spectra, integrating the analysis of these with the associated changes in histone acetylation induced in the epigenome. We discuss the application of the method in the context of basic and translational sciences.

Functional genome-wide analysis: a technical review, its developments and its relevance to cancer research.

A technique has emerged over the past decade combining chromatin immunoprecipitation with DNA microarray analysis. This is a powerful and sensitive strategy that has been used extensively to characterise protein interactions with chromatin and epigenetic changes such as acetylation and methylation throughout the genome of different organisms. This technique has revolutionised our understanding of molecular genomics, continues to be widely used and is currently being applied in novel areas of cancer research. In this publication we review the historical context of this technology and offer current and future perspectives on how this technique is currently being developed and modified to allow its use in novel areas of research. We discuss the potential for this technique and its ongoing important role in biological research particularly in relation to cancer research. We also offer insight into the potential clinical application of this technology in stratified medicine, particularly in the field of cancer therapy.

Metabolomics in toxicology and preclinical research.

Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context.

Systems toxicology.

The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity.

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing.

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.