The Ferryman

Innovation from Discovery to Application

The theme of the ACS meeting activities in Boston the next few days is one close to our values and current attention with Douglas Connect and our communities and partners: Innovation from Discovery to Application.

I will present on a few of our initiatives on this innovation path at the meeting in Boston and will upload the presentations on the net (including here).

Look forward to interacting in Boston or virtually!

Barry

Monday 17 August
8-10.30, room 103
Session on Workflow Tools & Data Pipelining in Drug Discovery
chaired by Tim Dudgeon and Erin Davis

9.30
Workflows supporting drug discovery against malaria
Barry Hardy, Thomas Exner and Alessandro Contini

The goal of Scientists Against Malaria (SAM) is the discovery of novel anti-malarial compounds. SAM supports virtual drug discovery organizational structures collaborating on target selection and modeling, protein expression and assay development, computational drug design, and screening. 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. Workflows were developed for consensus virtual screening of candidate malarial kinase inhibitors including docking, pharmacophore-based screening and free energy-based molecular simulations. The models were applied to the discovery of active ligands against a novel target with previously unknown structure or ligands. The workflows were extended to include OpenTox model web services to prioritize drug candidates according to their predicted toxicities, supporting a weight of evidence categorization of candidate molecules according to their activity and toxicity profiles.

DOWNLOAD SAM Drug Discovery Presentation  Download 150817 SAM ACS

13-18.00, room 103
Session on The Growing Impact of Openness in Chemistry: A Symposium in Honor of JC Bradley
chaired by Andrew Lang and Antony Williams

14.55
OpenTox - an open community and framework supporting predictive toxicology and safety assessment
Barry Hardy

One important goal of OpenTox is to support the development of an Open Standards-based predictive toxicology framework that provides a unified access to toxicological data and models. OpenTox supports the development of tools for the integration of data, for the generation and validation of in silico models for toxic effects, libraries for the
development and integration of modelling algorithms, and scientifically sound validation and reporting routines.

The OpenTox Application Programming Interface (API) is an important open standards development for software development purposes. It provides a specification against which development of global interoperable toxicology resources by the broader community can be carried out. The use of OpenTox API-compliant web services to communicate instructions between linked resources with URI addresses supports the use of a wide variety of commands to carry out operations such as data integration, algorithm use, model building and validation. The OpenTox Framework currently includes, with its APIs, services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, reporting, investigations, studies, assays, and authentication and authorisation, which may be combined into multiple applications satisfying a variety of different user needs. As OpenTox creates a semantic web for toxicology, it should be an ideal framework for incorporating toxicology data, ontology and modelling developments, thus supporting both a mechanistic framework for toxicology and best practices in statistical analysis and computational modelling.

In this presentation I will review the recent OpenTox-based development of applications including the ToxBank data infrastructure supporting integrated analysis across biochemical, functional and omics datasets supporting the safety assessment goals of the SEURAT-1 program which aims to develop alternatives to animal testing.

Finally, I will provide an overview of the working group activities of the newly formed OpenTox Association which aim to progress the development of open source, data, standards and tools in this area.

DOWNLOAD OpenTox Presentation: Download 150817 OpenTox ACS

Tuesday 18 August
13.30-17.00, waterfront 1A/1B
Session on Current Topics in Chemical Safety Information
chaired by Leah McEwen and Ralph Stuart

15.40
eNanoMapper - A Database and Ontology Framework for Nanomaterials Design and Safety Assessment
Barry Hardy, Egon L. Willighagen, Janna Hastings, Markus Hegi, Lucian Farcal, Nina Jeliazkova, Haralambos Sarimveis

The eNanoMapper EU FP7 project is developing a data management and analysis infrastructure together with ontologies supporting the safety assessment activities of the European nanomaterials research and development community. The project addresses the requirements of safety assessment of nanomaterials by providing databases, analysis tools and ontologies for risk assessment and linking them with existing resources in this area.

The work involves close cooperation with the EC NanoSafety Cluster members and other international organisations such as the EC JRC, and the EU-US NanoEHS cooperation initiative. Their requirements guide the development of tools for experimental design, model building, systems biology, and meta analysis across multiple datasets.

An ontology for nanosafety research is being developed to provide the following features: annotation of nanostructures and relevant biological properties, annotation of experimental model systems (e.g. cell lines), conditions, and protocols, complex search and reasoning capabilities, and the integration of data from existing nanotoxicology sources.

Systematic physicochemical, geometrical, structural, and biological studies of nanomaterials are rare in the public domain and data sharing is only just commencing, given the absence of readily available solutions for that purpose. eNanomapper will address that issue, as the establishment of a universal standardisation schema and infrastructure for nanomaterials safety assessment is a key goal of the project. It will catalyze collaboration, integrated analysis, and discoveries from data organised within a knowledge-based framework. It will support the discovery of nanomaterial properties responsible for toxicity, the identification of toxicity pathways and nano-bio interactions from linked datasets, ontologies, omics data and external data sources.

By interfacing with statistical and data mining tools, eNanoMapper aims to provide scientifically sound guidelines for experimental design as well as computational models for predicting nanotoxicity. These computational models will help to design safe nanomaterials and improve the risk assessment of existing nanoparticles.

This presentation will provide an overview of the progress made in the initial 18 months of the project, including outlines of the initial development releases of the data platform and ontology.

Download eNanoMapper presentation:  Download 150813 eNanoMapper ACS Boston

Wednesday 19 August
08.15 - 17.10, room 103
Session on Computational Toxicology: From QSAR Models to Adverse Outcome Pathways
chaired by Mohamed AbdulHameed

Using OpenTox to map toxicity data to AOPS
Barry Hardy

09.20
OpenTox provides a framework where data and model predictions can be retrieved from a federated set of data sources.

In this presentation we will discuss the concept of using relevant information (including its retrieval and organisation from multiple sources) in the development and application of Adverse Outcome Pathways (AOPs).

Analysis and discussion of the information obtained were used in conjunction with a collaborative wiki based approach to AOP development and interpretation.

We discuss the requirements and prospective solutions for the further computational development of AOPs e.g., using data and metadata to semantically annotate AOP nodes, challenge limitations in an AOP or propose new nodes for the AOP.

We will present meta analysis examples from the ToxBank data infrastructure project supporting integrated analysis across biochemical, functional and omics datasets supporting the safety assessment goals of the SEURAT-1 program which aims to develop alternatives to animal testing.

Download OpenTox, ToxBank and AOPS presentation  Download 150819 OpenTox AOP 1.2

 

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Roland Grafstrom and Pekka Kohonen win Scientific Lush Prize

eCheminfo Drug Design Meeting, Johns Hopkins, 9 - 11 Feb 2015

Innovation in Development and Translational Medicine

On the 13 February 2015 we will hold an InnovationWell workshop at Johns Hopkins, Baltimore.

The goal of the workshop is to discuss experiences, practices and solutions in drug development and translational medicine.

We will discuss case study experiences involving collaboration in drug and biotech discovery and development, obstacles experienced in practice and methods used to overcome barriers, approaches used to data sharing including IP and contractual issues, practices in knowledge management and innovation success.

We will subsequently flush out the real problems and issues involved in current practices in translational medicine, identify the strengths and weaknesses in current approaches being used and explore new strategies that might be of use to address and achieve improved translational success.

The workshop will be facilitated by Frank Hollinger (Sphaera Pharma), Michael Liebman (Strategic Medicine) and Barry Hardy (Douglas Connect).

Further information on the program can be found at
http://www.innovationwell.net/events/innovationwell-2015

OpenTox USA 2015

I am pleased to announce the program for the OpenTox USA 2015 meeting which will take place 10-12 Feburary at Johns Hopkins, Baltimore.

The goal of the meeting is to discuss and develop important components for driving 21st century approaches to safety assessment forward. We assume that collaboration driven by an open global platform and open standards will be a key success factor. Integrating heterogenous evidence supported by a common knowledge framework and ecosystem of tools and partners will enable practical application, judgements and decisions including industrial application and regulatory acceptance.

The program will involve conference sessions and associated hands-on workshops, poster session and knowledge cafes.

The main themes of the meeting are:

Data Science, facilitated by Barry Hardy (Douglas Connect)
Adverse Outcome Pathways, facilitated by Stephen Edwards (US EPA)
Exposure Modelling, facilitated by Tim Pastoor (Syngenta)
Integrating Evidence and Analysis, Thomas Hartung (Johns Hopkins)
Risk Assessment & Management Applications, Grace Patlewicz (Du Pont)

We are open for submission of abstracts for consideration for the program.

Further information on the program can be found at
http://www.opentox.com/events/opentox-usa-2015

On behalf of the OpenTox Community and the Organising Committee.

Related articles

Evidence-based Toxicology Collaboration

Innovation in Predictive Toxicology

OpenTox USA 2013 program and goals

OpenTox USA 2013 program (Cheminfostream)

OpenTox USA 2013 program

Video: OpenTox Toxicology Framework

eCheminfo drug discovery workshop in Oxford this year will work on anti-malarial case studies

We are organising our next eCheminfo hands-on drug design workshop in Oxford running 21 - 25 July:

http://www.douglasconnect.com/events/echeminfo-2014

Details on the program which we will run at St Hugh's College:
http://www.douglasconnect.com/dd2014/echeminfo2014.pdf

As in previous workshops the emphasis is on problem solving, practical hands-on use of methods and software applied to drug design problems, and working together throughout the week.

This year we will offer a neglected disease case study focus expanding on the initial collaboration activities of the Scientists Against Malaria initiative. We plan to try to develop and test most promising designs and predictions as workshop followup.

 

Related articles

eCheminfo drug discovery workshop, Oxford, 21 - 25 July

eCheminfo Drug Design workshop, bursary

Goodbye Patrik, we will miss you.

How malaria defeats our drugs

A Shared Moment of Great Happiness

Barry Hardy and Spela Predan, Just Married.

 

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.