What are key innovation questions for the field of predictive toxicology? I propose we discuss the following questions at our Knowledge Cafe at the #OpenTox 2011 meeting in Munich. We can use the discussions as a basis to formulate an innovation white paper to provide direction to innovators who can accelerate developments in the field with strategy and technology development.
A. Mechanistic Strategies - What are the key innovations needed to accelerate progress?
B. Predictive Metabolism - What is needed for a complete and reliable prediction of metabolites?
C. Computational Chemistry - Emerging challenges and opportunities in receptor-mediated predictive toxicology
D. Systems Biology - How can we bridge the divide between modelling molecular pathways and quantitative prediction at the organelle level?
E. Integrated Analysis - Experimental designs for optimising biomarker discovery
F. Kinetics - Extrapolating in vitro data to model human hazard and exposure
G. Weight of Evidence - Developing holistic approaches to compound profiling and prioritisation-based decision making
H. Read Across and Categories - What are the key components for a more rigorous approach to a best practice?
I. Regulatory Needs - How do we accelerate the acceptance of emerging scientific methods in regulatory applications?
J. High Content Assays - What information can they provide today and what are the key gaps requiring new innovation?
#OpenTox A la Koh! Njuah! Aleh Aleh! Greetings from the #SETAC #Africa workshop group here to the #OpenTox community. We find the tools interesting and would like more workshop activity and tutorials in the future. We are interested in applying tools to assessing the quality of our water, pollution from pesticides, effects of petroleum products on our communities. We are interested in assessing toxicity data, predicting acute toxic effects, evaluating longer term effects on human health such as development and reproductive toxicity, and applying ecotoxicity models for environmental risk assessment of our ecosystems.
A recording of the OpenTox presentation on OpenTox as an Open Source platform and semantic web for toxicity prediction, delivered by David Gallagher and Sunil Chawla at the ACS Spring 2011 meeting, is available at the following link:
Abstract submissions should be completed by 30 April for consideration for the conference program and bursary awards. Poster abstracts will continue to be accepted through 30 June, to be eligible for meeting-based review and innovation merit awards.
Slideset for "Ontology Development in support of Predictive Toxicology Use Cases & Services" presented by OpenTox Coordinator Barry Hardy (Douglas Connect) at the OpenTox-EBI Industry forum workshop on Toxicology Ontology held at the EMBL-EBI campus, Hinxton, Cambridge, UK, 15-17 November 2010 is available as a download from:
The ontology workshop discussions were I believe very productive and will undoubtedly lead to further communications and important proposals in months to come. Interact and stay in contact with us on these critical interoperable infrastructure developments in 2011 and beyond!
On Sunday May 30 we host an OpenTox Workshop near Berlin in Potsdam that will bring many leading international research program directors and leaders together to discuss how collaboration and the increased linking of resources over the World Wide Web could progress human safety research and safety assessment. By linking resources and data increasingly powerful computer-based models can be built for predicting and avoiding unwanted adverse toxic side effects of drugs, chemicals, ingredients in soaps and cosmetics, pesticides etc. thus enhancing human safety and protecting the environment better. Such methods should also eventually lead to the replacement of many animal experiments.
During the workshop we will apply a variety of design, informatics and modelling methods to predictive toxicology problems guided by workshop leaders with expertise in the approaches used. A case study approach will additionally be followed so that groups can work together throughout the week on their case study problems. The case studies will also be developed virtually before the workshop week with support extended afterwards for further work including experimental testing of interesting results and hypotheses developed. The virtual aspects of the case study work will additionally be supported by the Synergy and OpenTox infrastructures and related Collaboration Pool and pilot collaboration study.
Case studies will focus on the development of innovative integrated testing strategies applied to the problem of predicting the toxicity of a molecule. Such strategies are becoming an increasingly important part of drug design strategies so as to remove toxic liabilities as early as possible in the design processs. REACH legislation is also requiring organisations in coming years to carry out a more extensive safety testing of all chemical ingredients in a variety of products ranging from consumer products to food to agrochemicals. Related to this activity is the relatively unsatisfactory use of animal experiments to predict human toxicity, which are not only complex and expensive, but also often do not predict human effects well, if at all. Hence new approaches combining computational modelling, in vitro assays, systems biology, stem cell technology etc. are required.
We will apply techniques to the study of existing knowledge (e.g., from adverse events, biological literature, pathway models etc.) to help support mechanism-based hypotheses and strategies. Modelling techniques based on data-mining, database searching, and read-across will be applied to chemical categories. Integrated QSAR-based models supported by the new OpenTox infrastructure will be used to build properly validated models including estimation of applicability domain. We will also research ADME and kinetics properties of structures as relevant to their toxicity profiles. We will attempt to predict primary metabolities based on P450 metabolism simulation and model the potential toxicities of metabolites. Population-varied physiologically-based ADME Simulations will be carried out for in vitro-in vivo extrapolation, exposure estimation and to study the variation across individuals and populations. We will also apply workflow techniques to the combination of methods and Bayesian networks to the evolution of weight of evidence based consensus predictions.
The most promising strategies and predictions developed will be used to design experimental human toxicity-oriented in vitro assays which will be run after the workshop as part of the virtual case study extension work. Both computational and experimental work will be documented according to industry best practices in a collaborative electronic laboratory notebook. We will attempt to develop new combined in silico - in vitro strategies superior to existing approaches which should help advance the field and industry testing and regulatory needs.
Through the time spent working and discussing together combined with the availability of a variety of leading software and expert support from workshop leaders, workshop participants should take home ideas and learning to help accelerate their own projects related to safety design and risk assessment. The location and atmosphere in Oxford is also an ideal background for networking, getting to know your peers and joining the ongoing eCheminfo community of practice activities. As is often common with eCheminfo gatherings the workshop usually attracts a variety of backgrounds including industry, academia and government research instititutes and from many different countries. We also welcome the participation of non-modelling specialists from different areas of chemistry, biology and toxicology to participate and bring an interdisciplinary interaction to the collaborative group work.