Session 6: Read Across Use

Read Across Use of Alternative Evidence in Replacement Research and Safety Assessment supported by OpenTox and ToxBank
OpenTox Euro 2014 speaker: Barry Hardy
PRESENTING AUTHOR: 

Barry Hardy

INSTITUTION / COMPANY : 

Douglas Connect GmbH, Switzerland

AUTHOR(S): 

Barry Hardy, Glenn Myatt (Leadscope), Micha
Rautenburg (in silico toxicology), Pekka Kohonen
and Roland Grafström (Karolinska Institutet)

WHEN: 
Wed, 24. Sep. 2014

REFERENCES:

1) Hardy, B. et al, Collaborative Development of Predictive Toxicology Applications, Journal of Cheminformatics 2010, 2:7, 31 August 2010.
2) Hardy, B., Apic, G., Carthew, P., et al. (2012). A toxicology ontology roadmap. ALTEX 29, 129-137.
3) Hardy, B., Apic, G., Carthew, P., et al. (2012). Toxicology ontology perspectives. ALTEX 29, 139-156.
4) Kohonen, P., et al, “The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing”, Molecular Informatics, Special Issue: Advances in Computational Toxicology, (2013), Volume 32, Issue 1, 47–63.

ABSTRACT CONTENT / DETAILS:
Data on SEURAT-1 Gold Compounds (SGCs) were obtained from the literature and organised and made available through the ToxBank wiki and data warehouse.

The data integration included transcriptomics data from TG-Gates, assay data from PubChem, toxicokinetics data and parameters from the literature, and in vivo data resources. Interoperability between ToxBank components and other resources was based on service implementation of OpenTox standards.

Analysis methods for Read Across, enriched meta analysis of multiple omics and functional data, background knowledge from GO ontologies and Kegg pathways, and pathway visualisation were developed and applied to the SGCs.

We present an analysis case study for Doxorubicin based on publically available data examining the variation of pathway interactions as a function of dose and time.

Using SGC examples, we discuss the differing information requirements and solutions for computational and expert-based components to Read Across and Weight of Evidence for the following contexts with consideration of the value and current limitations in Alternative-based evidence:

a) Hypothesis-driven mechanistic-based research;
b) Predictive goal of an integrated testing strategy;
c) Incorporation of evidence in safety assessment decision making.

The role of current studies and methods in providing guidance supporting Read Across practice and application development will be discussed.