connecting people and data for decision making in safety...
TRANSCRIPT
Nat ional Academy of Sciences Workshop
Informing Environmental Health Decis ions Through Data Integration
W as hington DC, 20- 21 February, 2018
Connecting People and Data for Decis ion Making in Safety Assessment
Barry Hardy, CEO, Douglas Connect and President , OpenTox Associat ion
Overview
• Greater Investment in Data Practices & Data Science
• Better Integration of Data Science to enable Program Goals
• Stronger Relationships between End Users and Data Generators
Knowledge Work on the Is lands
Knowledge Work Together
OpenTox and Open Components and Standards
Feature GET POST PUT DELETE
Compound GET POST PUT DELETE
Dataset GET POST PUT DELETE
Ontology GET POST PUT DELETE
Algorithm GET POST PUT DELETE
Model GET POST PUT DELETE
AppDomain GET POST PUT DELETE
Validation GET POST PUT DELETE
Report GET POST PUT DELETE
www.jcheminf.com/content/2/1/7
Investigation (Study, Assay) GET POST PUT DELETE
<- ToxBank API addition to cover biological data
Authorisation & Authentication GET POST PUT DELETE
Init ial OpenTox Vis ion, Framework and Prototyping Proposed the components and specif ications for a semant ic web for toxicology
Collaborative development of predictive toxicology applications Journal of Cheminformatics 2010, 2:7 doi:10.1186/1758-2946-2-7 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
Open Access publication available at www.jcheminf.com/content/2/1/7
Lost in Translat ion
Consensus on need for Common Language and Ontology
• See perspectives and roadmap published in A Toxicology Ontology Roadmap ALTEX 29(2), 129- 137 and Toxicology Ontology Perspectives 139 - 156 (2012)
• Available online in Open Access mode from www.altex.ch • Barry Hardy (Douglas Connect and OpenTox), Gordana Apic
(Cambridge Cell Networks), Philip Carthew (Unilever), Dominic Clark (EMBL-EBI), David Cook (AstraZeneca), Ian Dix (AstraZeneca & Pistoia Alliance), Sylvia Escher (Fraunhofer Institute for Toxicology & Experimental Medicine), Janna Hastings (EMBL-EBI), David J. Heard (Novartis), Nina Jeliazkova (Ideaconsult), Philip Judson (Lhasa Ltd.), Sherri Matis-Mitchell (AstraZeneca), Dragana Mitic (Cambridge Cell Networks), Glenn Myatt (Leadscope), Imran Shah (US EPA), Ola Spjuth (University of Uppsala), Olga Tcheremenskaia (Istituto Superiore di Sanità), Luca Toldo (Merck KGaA), David Watson (Lhasa Ltd.), Andrew White (Unilever), Chihae Yang (Altamira)
Based on Proceedings from the Toxicology Ontology Roadmap Workshop EMBL-EBI Industry Programme Workshop
16 -17th November 2010, Hinxton, UK
Conversat ions overcoming Language Barriers
Bioclipse-OpenTox Integration – See Application example in Chapter in Open Source Software in Life Science Research: Practical Solutions to Common Challenges in the Pharmaceutical Industry and Beyond (Woodhead Publishing Series in Biomedicine) edited by Lee Harland and Mark Forster (30 Oct 2012)
Toxicity Predict ion – inspiring and enabling third part ies
OpenTox Associat ion Founding Principle (2015)
“The purpose of the Association is to promote the community-based exchange and use of open knowledge, methods, tools, data, reference resources, and standards including OpenTox Software and the OpenTox Application Programming Interfaces in the scientific activities of predictive toxicology, safety assessment and risk management, including the “3Rs” goal of the Reduction, Refinement and Replacement of Animal Testing.”
Article 4.1
OpenTox Community Act ivity and Hackathons
Facilitating Interactions and Best Practices
Warehouse
Gold Compounds Database
Biobank
Users access compounds, biological materials, data and models for experimental planning and integrated analysis of experimental results
Data Models
SOPs Compounds
SOPs Biological Materials
Data Models
RES
www.toxbank.net
Need for Process and Protocols
Investigator Principal Investigator
Use templates or define new
templates
Generate and enter data
Generate and write protocol
Review protocol
Upload/update and assign: - summary info - access level - keywords
Send email alert Investigator
Register interest
Investigator
Investigator
Search for information
Access protocols and data
Request access to confidential information
Bilateral agreement
Phase 2: Integrated data analysis
Other sources
Phase 1: Unified data access
Review data
Comment
EUToxRisk case study program
Training Testing / Application
Cmpd X is part of a group of cmpds with similar MoA/shared KE
Cmpd
X is
par
t of a
gro
up o
f cm
pds w
ith si
mila
r st
ruct
ure
Cases of initial information
AO blinded (test) AO unknown (real)
Case 3 (biol RAX)
grouping & prediction algorithms
Haza
rd p
redi
ctio
n Ri
sk a
sses
smen
t
RAX
ab initio procedure
optim
isatio
n cy
cles
Case 2 (QSAR)
Case 1
Case 4 (ab initio)
Project case
studies
mechanistic rationale
Case 1 ‚Case 2‘ Case 3
Case 4 (ab initio)
Case 3 Case 4 (ab initio)
No YES
Case 1 Case 2
YES
No
Project industry use case studies
• Four different case study scenarios based on available information.
• Iterative approach to optimize test system selection & IATA
development.
Omics Analysis - Access ing TG- GATES in KNIME
The workflow first gets a list of all available samples in TG-GATES for valproic acid. It then selects the repeated dose samples for rat in vivo with the highest exposure concentration and downloads the fold changes, averages them over the three replicates and then select all genes with fold changes above 2.0 or below -2.0. These are then visualized as heat maps where one can review the fold changes over time (4, 8, 15 and 29 days).
Processing and Visualising Toxicogenomics Data with Garuda - OpenTox
Dashboard
“Social” network
Cell designer Percellome
Next Generat ion OpenTox Expanded to Global Open Platform for Risk Assessment
EU-funded e-infrastructure project
Data Management and Workf lows
Principles as a Foundat ion for Best Pract ice
Quality Reliability
Robustness
Interoperability
Reproducibility
Harmonisation
Completeness
Open
Confidence
The journey started with Collaborative development of predictive toxicology applications Journal of Cheminformatics 2010, 2:7 doi:10.1186/1758-2946-2-7 Open Access publication available at www.jcheminf.com/content/2/1/7
Value Ext racted f rom Data Science and Metadata
Integrated Test ing St rategy
A ToxHQ Collaboration between Procter and Gamble & Douglas Connect
Title
Conversat ion with Weida Tong (FDA) at SOT 2017 on reproducibilit y …
… leading to a ToxHQ collaboration project we discussed at the Global Summit on Regulatory Science in Bras ilia
https://www.linkedin.com/pulse/towards-reproducible-silico-practice-via-opentox-barry-hardy
© 2015/2016, Johns Hopkins University. All rights reserved.
10 approved drugs
Evidence Stream 1 Systematic literature review of animal and human published
studies
Evidence Stream 2 Tox21/ ToxCast in vitro mechanistic
data
Evidence Stream 3 Human Adverse
Events
Tox 21 Project
Evidence Integration
Hubert Dirven (Norwegian Institute of
Public Health)
Ahmed Abdelaziz (Douglas Connect)
Maja Brajnik (Douglas Connect)
Main question: How well do the in vitro tests predict the liver outcomes in animals (mice, rats, Beagle dogs and NHPs)
and humans?
Omics – Examples of Variations in Biological Data
Container technology providing reliable delivery of code and data
In silico toxicology (IST) protocol consort ium
• An international consortium including regulators, government agencies, industry, academics, model developers, and consultants across many different sectors
• This consortium initially developing the overall strategy • Working subgroups are/will be developing individual in
silico toxicology protocols for major toxicological endpoints, including genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity, …
• Working subgroups are open for additional participation
Courtesy of Glenn Myatt
Combining Tradit ional and Modern Ref lect ions
Integrat ing Ontology for Nano Safety Assessment
NanoCommons
NanoCommons
Discussions preparing for Managing Crisis Situat ions
nanoehs.enanomapper.net
Our Knowledge and Innovat ion Future
