The Ferryman

OpenTox 1.0 - what we have reached on its third birthday

 


On the eve of its 3rd birthday, I told the story so far of our development of OpenTox in Slovenia last week.

The lecture (slides and video) recorded at the Josef Stefan institute in Ljubljana on "OpenTox - the creation of a semantic web for toxicology" is available at:
http://videolectures.net/solomon_hardy_semantic/

I look forward to that future "Sixth Sense" journey interoperating with OpenTox to revisit the Tamboti Trees in South Africa and the Mopane Trees in Namibia, and to test the delivery of safety advice from the distributed semantic knowledge of OpenTox 3.0 use cases in the field :)!

Innovation Questions for the field of Predictive Toxicology

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?



Innovation in Predictive Toxicology (#OpenTox Munich meeting program)

The preliminary program with schedule for the #OpenTox InterAction Meeting in Munich in August has been loaded at:
Innovation in Predictive Toxicology
9-12 August, Munich, Germany
http://www.opentox.org/meet/opentox2011/opentox2011

Abstracts for the poster session and awards are still being accepted through June at:
https://www.easychair.org/conferences/?conf=opentox2011

There is no registration fee to attend the conference but places are limited to 100 attendees.
Please complete the registration application form while still available at:
https://www.surveymonkey.com/s/opentox2011

Innovation in Predictive Toxicology

We are holding an OpenTox InterAction Meeting, in Munich, Germany (10-12 August 2011 on Innovation in Predictive Toxicology.

Further information including a preliminary list of speakers and topics, and links to abstract submission and registration forms is located at:
http://www.opentox.org/meet/opentox2011

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.

Registration should be completed using the form located at
https://www.surveymonkey.com/s/opentox2011

Registration involves no fee, but please note that places are limited to 100 participants, and we will have to close registration once our confirmed invitation and acceptance list is full.

A pre-conference OpenTox workshop on new developments in methods, REACH-relevant models and applications will be held 9 August.

Scientists Against Malaria - our first step to creating a Collaborative Learning Machine against Neglected Diseases

Last year we formed the “Scientists Against Malaria” (SAM) collaboration to apply modern drug design and modelling techniques in combination with industry standard infrastructure and interdisciplinary science to help develop new treatments against Malaria. The group’s first project assembles a number of leading academic researchers together with smaller innovative companies who are collaborating to develop novel inhibitors active against the Plasmodium parasite.

 

This is our first step in creating a collaboration learning machine for our community to enable and accelerate knowledge flow to progress the scientific research needed to develop new treatments against neglected diseases, which include other parasitic and tropical diseases, and diseases such as ALS which devastate people's health and are currently without any available treatment solutions.

Our drug design project involve situations when a number of partners collaborate to jointly solve molecular design problems as an early stage step in a drug discovery situation. The partners may involve commercial organisations, academic labs, and individual consultants who form a Virtual Organisation (VO) to collaborate on running the project, that typically has been historically carried out at a pharmaceutical organisation. The knowledge and experience of the partners involved is a critical resource and success factor for the project as is the ability to collaborate effectively. Additional resources include computer software and machinery for molecular design, modelling and virtual screening, experimental lab facilities for running assays and experiments on predicted hits for the problem studied, and supporting Information and Communications Technology (ICT) infrastructure. A significant amount of activity involving analysis, interpretation of results, synthesis and discussion is involved in many steps of the research process.

 

Computer-based models of Protein targets, Protein-Ligand and Protein-Protein interactions are built based on existing knowledge from crystal structures, physical chemistry and applications of bioinformatics and cheminformatics methods.  A variety of methods including virtual screening, docking, pharmacophore-based design and free energy simulation methods are applied to the design of drug candidate molecules and their affinity for the target based on interactions such as involving specific hydrogen bonding and hydrophobic interactions with the active site of an enzyme.  Holistic approaches to design also take into account specificity, cross-target interactions, Lipinski’s rule of 5 on druglikedness, ADME and toxicity properties of candidate molecules.  Predictions are tested in the laboratory using a variety of experimental screening methods. High Throughput Screening (HTS) can be used to examine the activities of libraries of molecules against a target, whereas High Content Assays may probe a specific toxicity mechanism and property of a molecule.

 

A Lessons Learned process is run at the end of every significant process in the collaborative research workflow and prioritised lessons are documented into the VO knowledge base. Best Practices are agreed and documented at the start of the project. If best or better practices are discovered during the Lessons Learned process (e.g., on discussing “what went well”), they are documented into the VO knowledge base for future reference.

 

A complex event-driven engine is used to track all significant events occuring during the collaborative work and to provide recommendations with regards to traffic light situations (e.g., green: positive, red: negative, yellow: uncertain) where yellow situations may trigger discussion and further actions. The combination of people and infrastructure may evolve and improve as activity expands, thus becoming a Collaboration Learning Machine for Drug Discovery and Neglected Diseases Research.

 

I will discuss the activities of the Scientists Against Malaria (SAM) consortium at the BIO-IT conference in Boston, taking place 12 – 14 April 2011 in its collaborative drug discovery session (http://www.bio-itworldexpo.com/Bio-It_Expo_Content.aspx?id=101305). SAM was formed in 2010 from the InnovationWell Neglected Diseases Collaboration Pool as a virtual drug discovery organization to collaborate on the design of kinase inhibitors against the Plasmodium Malarial parasite. Work activities have included target selection and modelling, protein expression and assay development, computational drug design, and screening. Supported by developments on the EU FP7 funded SYNERGY and OpenTox projects, a combination of interoperable information systems, ontologies and web services were designed and deployed to manage the data, documents, computational and assay results, activity and toxicology predictions, as well as dashboards to track project progress and to support decision making. We will discuss our results, experiences and lessons learned to date, and future directions and opportunities for collaborative drug design based on our virtual organization approach.

 

Collaborative development of predictive toxicology applications

The following initial paper on OpenTox has now been published and is available in preliminary form:

Collaborative development of predictive toxicology applications
Barry Hardy, Nicki Douglas, Christoph Helma, Micha Rautenberg, Nina Jeliazkova, Vedrin Jeliazkov, Ivelina Nikolova, Romualdo Benigni, Olga Tcheremenskaia, Stefan Kramer, Tobias Girschick, Fabian Buchwald, Joerg Wicker, Andreas Karwath, Martin Gutlein, Andreas Maunz, Haralambos Sarimveis, Georgia Melagraki, Antreas Afantitis, Pantelis Sopasakis, David Gallagher, Vladimir Poroikov, Dmitry Filimonov, Alexey Zakharov, Alexey Lagunin, Tatyana Gloriozova, Sergey Novikov, Natalia Skvortsova, Dmitry Druzhilovsky, Sunil Chawla, Indira Ghosh, Surajit Ray, Hitesh Patel and Sylvia Escher
Journal of Cheminformatics 2010, 2:7 (31 August 2010)
http://www.jcheminf.com/content/2/1/7

Please feel free to circulate in the community and to your contacts who might be interested. Thanks!

And a special thanks to all who have contributed to advancing this work, including our advisors, and growing community of friends, interactions and partners!

Barry 

OpenTox Workshop in Potsdam to discuss collaborative approach to linking resources to improve human safety

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.

More details on program can be located at:

http://www.opentox.org/data/blogentries/public/opentoxworkshoppotsdam2010

Neglected diseases, HIV, and development work on the ground in communities

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!

Barry

Collaboration Pools:

OpenTox - predictive toxicology
https://www.surveymonkey.com/s/M7TFM6C

eCheminfo - drug discovery
https://www.surveymonkey.com/s/V6T2YSD
 
InnovationWell - life science innovation and knowledge management
https://www.surveymonkey.com/s/782L9DZ

InnovationWell Collaboration Pool Formation

We are establishing an InnovationWell Collaboration Pool of individuals and organisations who have an interest in collaborating together in areas of healthcare and life science innovation. For example, a selection of Pool members could participate in a collaborative life science, systems biology or predictive toxicology project, develop a funding proposal or response to a call opportunity together, or develop an innovation or best practice.

To join the InnovationWell Collaboration Pool please complete the short form located at https://www.surveymonkey.com/s/782L9DZ

Collaborations will take a virtual organisation approach, i.e., partners can bring contributing knowledge, computational or experimental capabilities to a partnership for the duration of a project or other endeavour.

We will run two such virtual organisation (VO) projects for the first time this year starting later this Spring:
A) Drug Design project which will examine the application of a variety of leading modelling and design approaches to novel target kinases, to experimentally test predictions, and to initiate a best practices virtual screening resource.
B) Predictive Toxicology project to apply a combination of in silico and in vitro approaches to predict in vivo toxicity including exposure.

Both VOs will be supported by a variety of leading modelling and design software, informatics infrastructure, and collaborative content management and electronic lab notebook systems.

The VOs will be supported by knowledge-oriented collaboration services developed under the FP7 Synergy research project, including a reactive complex event driven engine, collaboration moderator, collaboration pattern services and partner knowledge base.

The Predictive Toxicology VO will be supported by distributed REST-driven web services for data management, model building, validation and reporting, developed under the OpenTox Framework (http://www.opentox.org/)

We will also consider incorporation of Case Studies into the eCheminfo Drug Discovery and Predictive ADME/Tox workshops to be held in Oxford this summer. See http://echeminfo.com/

Barry Hardy PhD
InnovationWell 

Douglas Connect
Switzerland

Growing significance of communities and collaboration in discovery and development

Just saw an article I wrote for Future Science has come out as a Perspective:

Growing significance of communities and collaboration in discovery and development
Barry Hardy, Future Medicinal Chemistry, June 2009, Vol. 1, No. 3, Pages 435-449.
http://www.future-science.com/toc/fmc/1/3

Sorry, but I don't have the budget just right now to take the Open Access option, but there is some other open material available at the above link.

In summarising the drivers for the growing significance of communites and collaboration I introduced:

The benefits of community participation or collaboration should outweigh the costs to support a rational decision to pursue such routes.  Lions usually prefer to hunt as a group as the shared food from group kills offers a better return and lower risk than hunting alone; in a similar manner organisations may also choose to collaborate to have greater success in acquiring new resources or income. The current convergence of a number of factors appears to be driving up the R&D collaboration benefit/cost ratio. The drivers include:

1.      Scientific research is becoming more complex and multi-disciplinary, requiring researchers to move more away from “working in the expert’s box”.

2.      Our work, economy and society are becoming more knowledge-oriented. (I define knowledge here as including understanding gained from experience and involves individual and collective knowledge in addition to explicit knowledge such as intellectual property (IP).)

3.      Business models in the chemistry and pharmaceutical industry that worked fine historically, e.g., manufacturing products based predominantly on patents related to chemistry, appear to be increasingly lacking.

4.      The goals of translational and personalized medicine have stronger requirements for networked and collaborative approaches over discipline and time than the historically relatively linear drug discovery and development process.  Integrated services offer greater future value creation than stand-alone products.

5.      Patient Safety has become an issue of growing concern requiring new more integrative approaches to data, knowledge and disciplines.

6.      Computational Science continues to grow in importance, fueling overlaps and interactions between scientific disciplines including that of computer science.

7.      The maturing of the Internet-based World Wide Web including enhanced usability, services, social software and the semantic web, provide new community and collaboration resource opportunities.

8.      Challenging problems we face as a race such as global warming, energy management, population growth, and sustainable development are often linked to healthcare issues and are demonstrating the need and benefit for greater cooperation and at larger scales.

9.      Continuing education and learning throughout life has been growing in importance as knowledge workers go through greater numbers of career and job changes than in the industrial age.

10.  Work can increasingly be done anywhere on the planet where the best combination of costs and skills are available.  As Thomas Friedman discussed in his recent book, the “world is now flat” (1). A work objective can be broken into a workflow of numerous tasks, each of which may be done in different locations or by different organizations or individuals.

And I will add three more uncertain or controversial factors here:

11.  There is a growing importance of small and medium size enterprises (SMEs) collaborating in knowledge-oriented activity and growth in the global economy.

12.  As our modern life seems increasingly less rewarding beneath the surface, we need, search for and find new happiness from the benefits of taking advantage of new collaboration opportunities through interacting with others more.  In addition to needing better conversations for learning, work and self-development, we also simply need them psychologically and to feel good.  (Happier workers are also more productive ones.)

13.  Enabling international cooperation, collaboration and knowledge transfer in socio-economic areas such as healthcare, including building shared cultural meaning between different countries, races and cultures will significantly progress the security and prosperity of the world we leave to our children, whereas other current flawed political, military and unsustainable economic strategies will not.

Welcome your feedback and additions...

The Ferryman

(1) Friedman TL, “The World is Flat”, Picador, (2005).