Cheminfostream

Warren Delano RIP

It was only a couple of weeks ago we had Warren presenting on new PyMol developments at our eCheminfo community of practice program at Bryn Mawr:
http://echeminfo.com/comty_conf09delanow

What a shock and sadness to see this news in my email box today. Our thoughts are with his family and friends.

As a scientific community let's make sure that Warren's work continues and is built upon. He created something useful for others to benefit from, and the Open Source model allows that to continue!

You can post memories to the following blog page:

http://warrendelano.blogspot.com/2009/11/my-brother-warren.html

Barry Hardy
Founder & Director
eCheminfo Community of Practice
Douglas Connect, Switzerland

Satisfying REACH Requirements in Predictive Toxicology

The OpenTox workshop on "Satisfying REACH Requirements in Predictive Toxicology" to be held at the ISS in Rome 10-11 September 2009. 

Participants at the workshop will involve cross-industry users and regulatory experts in addition to solution developers and providers who will discuss the requirements and use cases of users in chemical toxicology evaluation and risk assessment, and including satisfaction of current and future requirements of the REACH legislation using alternative testing methods. The workshop format involves short presentations to provide user, regulatory and solution needs perspectives, followed by knowledge cafe discussions discussing use cases, challenges, issues, solutions, collaboration opportunities and ways forward in small groups.

PROGRAM

Thursday 10 September

08.30 Welcome Coffee

09.00 Introduction & Workshop Overview, Barry Hardy (OpenTox and Douglas Connect, Switzerland)

09.15 The Use of Computational Methods for the in silico  Prediction of Chemical Properties in REACH, Andrew P Worth (Systems Toxicology Unit, Institute for Health and Consumer Protection, European Commission -Joint Research Centre, Italy)

09.40 Automated Workflows for Hazard Assessment, Elena Fioravanzo (S-IN Soluzioni Informatiche, Italy)

10.05 OpenTox Predictive Toxicology Use Cases, Barry Hardy (OpenTox and Douglas Connect, Switzerland)

10.30 Coffee Break

11.00 Knowledge Café Discussions

12.30 Group Discussion

13.00 Lunch

14.00 Opportunities for using  Systems Biology Data for in silico  Modeling of Personalized Medicine, Richard D. Beger  (Division of Systems Toxicology, National Center for Toxicological Research, Food and Drug Administration, USA)

14.25 A Framework for Using Structural, Reactivity, Metabolic and Physicochemical Similarity to Evaluate the Suitability of Analogs for SAR-based Toxicological Assessments, Joanna Jaworska (Procter & Gamble, Modeling & Simulation, Biological Systems, Brussels Innovation Center, Belgium)

 14.50 Integration of Integrated Assessment Tools for Environmental Risk Assessment, Willie Peijnenburg (National Institute for Public Health and the Environment, The Netherlands)

15.15 Prediction of Animal Toxicity Endpoints for ToxCAST Phase I Compounds using a Combination of Chemical and Biological in vitro Descriptors, Alex Tropsha (Carolina Center for Computational Toxicology and Carolina Environmental Bioinformatics Research Center, University of North Carolina at Chapel Hill, USA)

15.40 Coffee Break

16.00 Knowledge Café Discussions

17.30 Group Discussion

18.00 Close

 

Friday 11 September

08.30 Welcome Coffee

09.00 Predictive Toxicology for Cosmetics - An Industry Perspective, Stephanie Ringeissen (Safety Research Department, L’Oréal R&D, France)

09.25 OECD (Q)SAR Application Toolbox: Progress and Ongoing Developments, (OECD, Paris, France)

09.50 Italian Specialty Chemical Industry Perspective on Predictive Toxicology, Maurizio Colombo (Health & Safety Evaluation, Industrial Regulation Management, Lamberti S.p.A., Italy)

10.15 Coffee Break

10.45 Knowledge Café Discussions

12.00 Group Discussion

12.30 Lunch

13.30 The Italian Chemical Industry and the REACH impact on SMEs, Antonio Conto (Chemsafe Srl, Italy)

13.55 Classification- and Regression-Based QSAR of Chemical Toxicity on the Basis of Structural and Physicochemical Similarity, Oleg Raevsky (Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds of Russian Academy of Sciences, Moscow, Russia)

14.20 Analysis of Toxcast Data and in vitro / in vivo Endpoint Relationships, Romualdo Benigni (Istituto Superiore di Sanità, Italy)

14.45 Coffee Break

15.15 Knowledge Café Discussions

16.30 Group Discussion

17.00 Close

More Information including Abstracts:

http://www.opentox.org/data/blogentries/public/opentoxworkshoprome09

Collaborative Development of Predictive Toxicology Applications

I enclose here an abstract and copy of the presentation for the Plenary Lecture "Collaborative Development of Predictive Toxicology Applications" that I presented in Istanbul on 6 July 2009 at the Fifth International Symposium on Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (CMTPI 2009).

Presentation

Download OpenTox-CMTPI 2009 Presentation 90706

Abstract

Collaborative Development of Predictive Toxicology Applications

Barry Hardy*^a, Christoph Helma^b, Nina Jeliazkova^c, Romualdo Benigni^d, Stefan Kramer^e, Andreas Karwath^f, Haralambos Sarimveis^g, David Gallagher^h, Vladimir Poroikovⁱ, Sunil Chawla^j, Sylvia Escher^k

This lecture will provide a perspective on the growing significance of community and collaboration approaches in predictive toxicology.  In part these challenges are technical and involve progressing issues related to cross-organisational, enterprise and application interoperability. Additional challenges include the development and application of best practices related to knowledge management, culture, organizational and industry development.

The EC-funded FP7 project “OpenTox” (www.opentox.org) is developing an Open Source-based predictive toxicology framework that provides a unified access to toxicological data and (Quantitative) Structure-Activity Relationship i.e., (Q)SAR models. OpenTox provides tools for the integration of data, for the generation and validation of (Q)SAR models for toxic effects, libraries for the development and integration of (Q)SAR algorithms, and scientifically sound validation routines. OpenTox will support the development of applications for non-computational specialists in addition to interfaces for risk assessors, toxicological experts and model and algorithm developers.

OpenTox is relevant for the implementation of REACH as it allows risk assessors to access experimental data, (Q)SAR models and toxicological information from a unified interface that adheres to European and international regulatory requirements including OECD Guidelines for validation and reporting.  The OpenTox framework is being populated initially with data and models for chronic, genotoxic and carcinogenic effects. These are the endpoints where computational methods promise the greatest potential reduction in animal testing required under REACH. Initial research has defined the essential components of the framework architecture, approach to data access, schema and management, use of controlled vocabularies and ontologies, web service and communications protocols, and selection and integration of algorithms for predictive modelling.  The initial results of this research and next steps will be discussed.

OpenTox has been initiated as a collaborative project involving a combination of 11 different enterprise, university and government research groups to design and build the initial framework.  Additionally numerous organizations with industry, regulatory or expert interests are being included from the start in providing guidance and direction.  The goal is to expand OpenTox as a community project enabling additional expert and user participants to be involved in developments in as timely a manner as possible. To this end, our agreed upon intention is to carry out developments in an open and transparent manner from the early days of the project, and to open up discussions and development to the global community at large, who may either participate in developments or provide user perspectives.  Cooperation on data standards, data integration, ontologies, integration of algorithm predictions from different methods, and testing and validation all have significant collaboration opportunities and benefits for the community.  Additionally, practices for building effective collaborations from the OpenTox community approach will be discussed.

About OpenTox

OpenTox - An Open Source Predictive Toxicology Framework, www.opentox.org, is funded under the EU Seventh Framework Program: HEALTH-2007-1.3-3 Promotion, development, validation, acceptance and implementation of QSARs (Quantitative Structure-Activity Relationships) for toxicology, Project Reference Number Health-F5-2008-200787 (2008-2011).

Project Partners

Douglas Connect^a, In Silico Toxicology^b, Ideaconsult^c, Istituto Superiore di Sanita'^d, Technical University of Munich^e, Albert Ludwigs University Freiburg^f, National Technical University of Athens^g, David Gallagher^h, Institute of Biomedical Chemistry of the Russian Academy of Medical Sciencesⁱ, Seascape Learning^j and the Fraunhofer Institute for Toxicology & Experimental Medicine^k

Advisory Board
European Centre for the Validation of Alternative Methods, European Chemicals Bureau, U.S Environmental Protection Agency, U.S. Food & Drug Administration, Nestle, Roche, AstraZeneca, LHASA, Leadscope, University of North Carolina, EC Environment Directorate General, Organisation for Economic Co-operation & Development, CADASTER and Bayer Healthcare

*Contact Address: Dr. Barry Hardy, OpenTox Project Coordinator and Director, Community of Practice & Research Activities, Douglas Connect, Baermeggenweg 14, 4314 Zeiningen, Switzerland

Overcoming the challenges to reducing animal experimentation through an Open Source community-based development of in silico methods

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 and  better curated public databases.

The routine application of these new generation models is however still rare, because

l  Toxicity data has been collected in a variety of different databases.

l  These databases use different formats, that are frequently not compatible with (Q)SAR programs

l  Many databases lack important information for (Q)SAR modeling (e.g. chemical structures)

l  It 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)

l  There is no straightforward integration of predictions from various programs

l  There is no commonly accepted framework for the validation of (Q)SAR predictions and many (Q)SAR tools provide limited support for reliable validation procedures

l  The 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:

l  A simple and intuitive interface for toxicological experts, that provides unified access to (Q)SAR predictions, toxicological data, (Q)SAR models and supporting information

l  An expert interface for the streamlined development and validation of new (Q)SAR models

l  An 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.

Do consider joining the OpenTox community effort through signing up on the website!

Blending meeting presentations with virtual community activity

Rich Apodaca made the suggestion to me that we should consider making presentations available from our face-to-face community of practice activities to the virtual.  We have actually taken this approach with eCheminfo and InnovationWell and both with virtual conferences and face-to-face meetings since we started the communities late 2003.  And I currently have a headache to solve - how can I combine such material into a useful community resource archive?

Another problem I have had is the level of effort required for such activity.  Technically we can do it but it takes time and resources.  Plus there is then editing and review.  And on top of that, there are all the complications on varying permissions that different participants may have for you.  At last's years Autumn meetings I just pulled back and went for the simpler solution of pdf file sharing through a wiki, as I could not deal with adding additional workload at that time.  Plus this kind of knowledge-sharing is usually mainly a cost rather than a revenue stream that can pay for the effort, and although there could be some possibilities there, it is not a major motivation for me to be spending my time on such a direction.

But tools are getting better and I am on the look out for what could be a better solution.  File sharing tools like box, video-sharing tools like youtube, widgets linking your presentations into LinkedIn or a Wetpaint wiki are all getting more user friendly.  But like U2's Bono I have not yet quite found what I am looking for.  Perhaps people have some suggestions to make?  Let me try some requirements for the solution:

- has content management and workflows for the content

- has self service for group members with permissions and review

- handles files, audio, video

- easy-to use live and playback multimedia editing and upload

- effective search over content including multimedia

- supports vocabulary, tagging

- works for variety of situations including face-to-face, virtual and blended

- supports user registration and profiles

- affordable

- usable

- Open Source would be nice

- interoperable with other collaboration and Web 2.0 tools so we can maintain context

------

- And for the specific eCheminfo context, also adding interoperable cheminformatics capability would be very nice!

I recently posted some related thoughts on Context, Google Wave and Colayer on the Ferryman.

Welcome your suggestions!

eCheminfo Virtual Community Activities in Cheminformatics

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:

https://www.linkedin.com/e/gis/1173/77EB680070FF/

I also really welcome suggestions from the community there on what you would like to see as further developments in coming years!

Barry

Preliminary Program for eCheminfo 2009 Drug Discovery Informatics Meeting Available

The eCheminfo 2009 community of practice meeting on drug discovery informatics will take place at Bryn Mawr College, Philadelphia 13-16 October 2009.

This annual community of practice meeting is taking place for the fifth time and brings together a unique combination of pharmaceutical and healthcare industry experts, principal investigators and researchers from the academic and government sectors, and leaders from innovative enterprises.  The smaller and more intimate meeting format pursued has fostered the type of collaboration not always found at large conferences.

The preliminary program with abstracts received so far is now available at http://echeminfo.com/COMTY_conferencesprog09 and will be updated as remaining abstracts are received.

The topics addressed this year will include Structure-based Drug Design Applications and Methods, Macromolecular Interactions and Networks, Data Analysis and Visualisation, PDB Ligands, and Predictive Toxicology.

A pre-conference best practices workshop on Binding Energy prediction will take place October 12, 2009.

This meeting will take place concurrently with the InnovationWell 2009 meeting addressing the topics of Collaboration in Discovery and Development, Translational Bioinformatics, Systems Biology and Biomarkers, Blood Brain Barrier modeling and Predictive Toxicology.

Below is a short summary of the program.

Latest Advances in Drug Discovery Informatics - eCheminfo 2009 InterAction Meeting
October 13-16, 2009
Bryn Mawr College, Bryn Mawr, Philadelphia, USA

Conference Link with Abstracts:
http://echeminfo.com/comty_conferences

Program as pdf download: Download ECheminfoProgramBrynMawr09

eCheminfo 2009 Program Summary

Monday 12 October
Pre-conference Workshop on Drug Binding Affinities
Co-Chaired by Scott Brown (Abbott Laboratories) and Judith Lalonde (Bryn Mawr College)

Tuesday 13 October
Structure-Based Drug Design Applications, Chaired by Alan Cheng (Amgen)

Macromolecular Interactions and Networks, Chaired by Emil Alexov (Clemson University)

Wednesday 14 October
Structure-Based Drug Design Methods, Chaired by Natasja Brooijmans (Wyeth)

Data Analysis and Visualisation Applications in Chemical Biology, Chaired by Brian Marsden (Structural Genomics Consortium Oxford)

Thursday 15 October
PDB Ligands, Chaired by John Westbrook (Rutgers University)

Predictive Toxicology, Co-Chaired by Richard Judson (US EPA) and Vladimir Poroikov (Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences)

Friday 16 October
Predictive Toxicology, Co-Chaired by Richard Judson (US EPA) and Vladimir Poroikov (Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences)

Contact:
Program: Dr. Barry Hardy, eCheminfo Community of Practice, Douglas
Connect. Tel: +41 61 851 0170. email: barry.hardy -(at)- douglasconnect.com

Meeting Support: Rob Reedijk, eCheminfo Community of Practice, Douglas
Connect. Tel: (416)978-0774. email: rob.reedijk -(at)- douglasconnect.com

Registration Enquiries: Nicki Douglas, Douglas Connect, Baermeggenweg
14, 4314 Zeiningen, Switzerland. Tel: +41 61 851 0461. email: echeminfo -(at)- douglasconnect.com

eCheminfo 2009 Drug Discovery meeting at Bryn Mawr - call for contributions

We will hold our fifth annual eCheminfo community of practice meeting on drug discovery informatics at Bryn Mawr College, Philadelphia 13 -16 October 2009.

We invite contributed papers from members of academic, government research and commercial organizations on areas of new research and innovation involving drug discovery research informatics. The work presented should involve innovative new method development or application to drug discovery problems and involving methods from computational chemistry, computational biology, cheminformatics or bioinformatics. Studies including experimental work in medicinal chemistry, screening, in vitro assay development, pre-clinical evaluation, lead optimisation and translational medicine are welcome.

Abstracts for talks (300-500 words) should be submitted to echeminfo -[at]- douglasconnect.com by 31 March 2009, and be accompanied by a short biography of the presenting author (300-500 words). Abstracts approved by the scientific organizing committee will be selected for scheduling on the conference program. Authors will be notified of acceptance as soon as a review of submitted materials takes place and at the latest by 15 April 2009. Abstracts for posters will continue be accepted for review through 31 August 2009.

The following sessions are currently planned:

Pre-conference Workshop on Drug Binding Affinities
chaired by Scott Brown (Abbott Laboratories) and Judith Lalonde (Bryn Mawr College)

Structure-Based Drug Design: The Roles of Conformation, Water and Hydrogen Bonds
chaired by Alan Cheng (Amgen)

Macromolecular Interactions and Networks
chaired by Emil Alexov (Clemson University)

Structure-Based Drug Design: Advanced Scoring Methods
chaired by Natasja Brooijmans (Wyeth)

Data Analysis and Visualisation Applications in Chemical Biology
chaired by Brian Marsden (Structural Genomics Consortium Oxford)

PDB Ligands
chaired by John Westbrook (Rutgers University)

Predictive Toxicology
chaired by Vladimir Poirikov (Russian Academy of Medical Sciences) and Richard Judson (US EPA)

Cheminformatics Workshop Week on Drug Discovery in Oxford

We are running the eCheminfo drug discovery workshop week at Oxford University this year the week of 20-24 July.

Workshop groups will study problems with hands-on examples using computational drug discovery methods and discuss issues highlighted by examples and Case Studies presented by instructors. A Case Study set with a focus on Kinases will be used to link all workshop activities throughout the week.

Workshop topics will include:

- Virtual Screening
- Structure-based Drug Design & Planning
- Ligand Optimisation & Library Design
- Structure Search, Similarity and Property Estimation
- Bioactive Conformations & Conformational Search
- Pharmacophore Modelling for Lead Identification
- Fragment-based Drug Design
- Free Energy-based Calculation of Binding Energies
- Modelling Reactions & Synthetic Feasibility of Workshop Libraries
- Application of ADME and Metabolic Property Prediction to Library Design

A Bursary Award will be used to support the attendance of a selection of academic participants, who may be working in any area of research related to drug discovery. To apply for the bursary please send an email with a) description of your research (ca. 500 words); b) your training needs (ca. 500 words), c) your CV to eCheminfo -[at]- douglasconnect.com by 27 February 2009.

More information on program can be found at: eCheminfo Drug Discovery Workshop 2009 in Oxford Program

Registration: Registration for eCheminfo Drug Discovery Workshop 2009 in Oxford

or contact Nicki Douglas at eCheminfo -(at)- douglasconnect.com

The Mukuni Project: Lions and Cheetah

I have posted a short summary with photos on our visit with the new Mukuni lions and cheetah conservation project located just outside Livingstone in Zambia at:

http://barryhardy.blogs.com/theferryman/2009/02/walking-with-lions-and-licked-by-cheetahs-a-visit-with-the-mokuni-project-in-zambia.html