This book provides a very useful reference and comprehensive summary of all recent/current significant Alternative Testing R&D FP6/7 projects in Europe, plus additional perspectives on other initiatives e.g., in US, Japan etc. It includes a chapter on #OpenTox.
Barry Hardy PhD Director, Community of Practice & Research Activities and OpenTox Project Coordinator (www.opentox.org)
We have had a lot of activity in recent months on the OpenTox project with regards to developing a linked data and resource infrastructure for the support of interdisciplinary predictive toxicology research and safety assessment. I enclose several links below including our recent overview workshop presentation in Potsdam, reports, demonstrations, technical links and interest groups. A paper will be published as an Open Access publication in coming weeks (reference below).
We welcome your joining this community and movement to work towards the common goal of safer products and a safer environment, supported by new alternative and advanced methods.
Your Resources If you have a useful resource you would like to see integrated into OpenTox, e.g., a database from your project to which an OpenTox web service could be added, please contact me to discuss.
OpenTox Demos (Please keep in mind these are early prototype applications and may not have features you want. We welcome requests from you for what you additionally need in these applications or others.) http://www.opentox.org/toxicity-prediction
Publication Reference Collaborative Development of Predictive Toxicology Applications, B. Hardy, N. Douglas, C. Helma, M. Rautenberg, N. Jeliazkova, V. Jeliazkov, I. Nikolova, R. Benigni, O. Tcheremenskaia, S. Kramer, T. Girschick, F. Buchwald, J. Wicker, A. Karwath, M. Gütlein, A. Maunz, H. Sarimveis, G. Melagraki, A. Afantitis, P. Sopasakis, D. Gallagher, V. Poroikov, D. Filimonov, A. Zakharov, A. Lagunin, T. Gloriozova, S. Novikov, N. Skvortsova, D. Druzhilovsky , S. Chawla, I. Ghosh, S. Ray, H. Patel, S. Escher, accepted 3 June 2010 for Open Access publication in J. Chemical Informatics http://www.jcheminf.com/ (2010).
We will hold an OpenTox workshop near Berlin on 30 May 2010 aimed to discuss developments and progress new actions on the interoperable development of predictive toxicology resources and applications including the importance of Open Standards, Interfaces, Data, Schema and Ontologies.
The workshop will include a variety of perspectives, a Knowledge Cafe discussion and a boat trip around the lakes to network and chat in a relaxed setting.
In addition to presenting and demonstrating on recent OpenTox developments, representatives from many leading international projects will participate to provide perspectives including Robert Kavlock, Director, National Center for Computational Toxicology (US EPA); Carl Westmoreland, Director, Science & Technology, Unilever Safety & Environmental Assurance Centre (Unilever); Emilio Benfenati, Professor and CAESAR Project Coordinator (Istituto di Ricerche Farmacologiche Mario Negri); Stephen Bryant, Senior Investigator and PubChem Leader, National Center for Biotechnology Information, National Library of Medicine (National Institutes of Health, USA); Jeffrey S. Wiseman, CEO (Pharmatrope); Egon Willighagen, Project Leader, Bioclipse and the CDK (University of Uppsala); Michael Schwarz, Professor and Coordinator of ReProTect (University of Tuebingen); Juergen Hescheler, Professor and Coordinator of ESNATS (University of Cologne); Horst Spielmann, Professor for Regulatory Toxicology (Freie Universität Berlin).
Neglected diseases such as parasitic infections reek havoc on many communities in different parts of the world. As part of our committment to responsible, sustainable development and a community culture, we will make neglected disease problems, where we evaluate we can make a significant difference, a goal of our collaborative virtual organisations in years to come. Please contact me to discuss your ideas and also consider joining the new Collaboration Pools summarised at bottom of this post. We can also work together on new funding opportunities.
However and also, my experiences in Africa, for example on our conservation trip to the remote Caprivi Delta region of Namibia: http://barryhardy.blogs.com/theferryman/2009/02/experiences-from-expedition-work-in-the-caprivi-delta.html (please keep in mind this post was based on a summary for my younger son for awareness!), was that "small contributions" can make a big difference. One story from that trip was the inability of a local clinic to deal with the torn foot of one of our party, and we ended up stitching him up with a veterinary kit back at base camp. Once that was done, how would he get around we asked, as there were no crutches to be had locally?! Discussing the incident around the camp fire afterwards, we came up with the simple solution of each throwing some money into a "needles and crutches" hat, and that was able to buy needles and crutches for the local clinic to keep them going for a couple of years, and it could be directly organised. So in this reality-focused context something like $200 made a bigger difference on the real problem for the future than a (possibly failed) major $100m program. A bit of a stretched analogy, but you probably get the point.
We intend to continue our support of sustainable development work in the community in Caprivi in community-involved wild life conservation development, and look forward to our next trip, and others in the community who might be interested. Let me know, if this might be for you too.
Here I would like to draw attention to a new local initiative in the area to help support the families affected by a widespread HIV infection epidemic. There is need for education, healthcare, and support of the many orphans left behind by parents who simply die from untreated HIV infection. Consider what you might do by volunteering some simple help and support to the work out there. The new center is called TAG Volunteers (TAG for think-act-grow):
http://www.tagvolunteer.com/ I vouch this is a real legitimate project as Ronel, the woman setting it up, was also very much involved in competently running the important activities at our base camp on our last visit, such as getting something to eat when we got back very tired and hungry from our trips into the bush!
Welcome your feedback. If you do decide to take some time out to volunteering in some way, I suspect you will find it rewarding. And it is also at the same time such a special and beautiful country to experience!
In a recent study by the European Chemical Bureau, it has been estimated that the new EU chemical legislation REACH will require 3.9 million additional test animals, if no alternative methods are accepted. The same study shows that it is possible to reduce the number of test animals significantly by utilizing existing experimental data in conjunction with (Quantitative) Structure Activity Relationship ((Q)SAR) models. Chronic and reproductive toxicity, in vivo mutagenicity and carcinogenicity are the endpoints that will require the largest number of test animals within REACH, because no alternative in vitro assays are currently available.
Recent (Q)SAR developments allow a much more accurate prediction of complex toxicological endpoints than a few years ago. This progress has been caused by (i) the development of improved (Q)SAR algorithms and (ii) by the availability of larger andbetter curated public databases.
The routine application of these new generation models is however still rare, because
lToxicity data has been collected in a variety of different databases.
lThese databases use different formats, that are frequently not compatible with (Q)SAR programs
lMany databases lack important information for (Q)SAR modeling (e.g. chemical structures)
lIt is hard to integrate confidential in-house data with public data for model building and validation
l(Q)SAR models have been published in a variety of different formats (ranging from simple regression based equations to full-fledged computer programs)
lThere is no straightforward integration of predictions from various programs
lThere is no commonly accepted framework for the validation of (Q)SAR predictions and many (Q)SAR tools provide limited support for reliable validation procedures
lThe application, interpretation, and development of (Q)SAR models is still difficult for most toxicological experts. It requires a considerable amount of statistical, chemoinformatics and computer science expertise and the procedures are labor intensive and prone to human errors.
The overall objective of the FP7-funded OpenTox is to develop a framework, that provides a unified access to toxicity data, (Q)SAR models, procedures supporting validation and additional information that helps with the interpretation of (Q)SAR predictions. OpenTox will be accessible at three levels:
lA simple and intuitive interface for toxicological experts, that providesunified access to (Q)SAR predictions, toxicological data, (Q)SAR models and supporting information
lAn expert interface for the streamlined development and validation of new (Q)SAR models
lAn application programming interface (API) for the development, integration and validation of new (Q)SAR algorithms
The OpenTox framework is being developed as an Open Source project to optimize the dissemination and impact, to allow the inspection and review of algorithms and to attract external contributors. Our approach is to closely collaborate with related projects (e.g. OECD QSAR toolbox, CADASTER, Leadscope’s ToxML development), industry users, developers and regulatory authorities to agree on common standards and to avoid duplicated and redundant work.
When I started the eCheminfo community of practice in late 2003 we focused initially on using the approach of virtual conferencing and communications to get the community started. More recently I have given more attention to developing face-to-face conference and workshop activity and initiating collaborative research. While on this journey it has been personally rewarding to have met and made contact with hundreds of scientists in the international community and to additionally be involved in supporting their networking, career development and research in drug design, discovery and modelling. It has also been rewarding to have just met so many great people and to have had the chance to interact with them, be it on a computer, in a workshop exercise, or on a punt trying to get down the river as we usually do when we are in Oxford. So far we seem to be better on computer-based physics than boat physics!
And so I have come full circle and can see the need to prioritise the virtual community aspects of eCheminfo further again, to support the continuation of all these worthwhile interactions in the community. So LinkedIn is one place to start. I have been on there for some years and we have had a group area, but have not really done much with it. It has primarily been useful for some introductions between people. However recent feature additions for discussion, posting of news, job announcements etc. have been added, so it seems worthwhile to try using it more for supporting continuing interactions in the community. So I am initiating today invitations to the eCheminfo community to join us there for discussion, news and networking on what is happening in the world of drug discovery informatics, cheminformatics, bioinformatics, etc. Use of the group is intended for scientific and professional exchange purposes only. As included in our mission we encourage cross-disciplinary cross-sector participation so from medicinal chemists in the pharmaceutical industry through toxicologists in government institutes through PhD students working on their modelling research problems are welcome!
To request joining the eCheminfo LinkedIn group please follow the following link and introduce yourself with a group joining request:
I had an interesting and productive expedition in the Caprivi Delta in Namibia at the end of 2008. I have posted a description of some experiences there on The Ferryman and look forward to more conservation and sustainable development work later this year and beyond.
But 2009 is here and we are all tired already of the pessimistic news of the year ahead!
Nevertheless, our new OpenTox Predictive Toxicology research project has been progressing and I encourage you to join the community for this exciting project.
We will be holding our discovery informatics workshop week in Oxford again in July, with the interesting addition of a case study approach on kinases this year. We are also adding a second week dedicated solely to Predictive ADME and Tox problems. Both weeks should be excellent group working experiences. Please visit the eCheminfo community site for more details.
We are currently planning our community of practice activity for the year, which will include an introduction of new virtual resources and activities, and the planning for our annual meeting at Bryn Mawr in October. We should make progress I hope on several initiatives including the new PDB ligands initiative of Marc Nicklaus (NIH), the virtual screening intiative and further collaborative projects. Do contact me on barry.hardy -(at)- douglasconnect.com to discuss further.