The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing

Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin P.; Grafström, Roland C.; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott A.; Myatt, Glenn J.; Rautenberg, Micha; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

doi:10.1002/minf.201200114

Cited by 39 publications

(33 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…But the toxicology field would benefit from even further developed integrated tools such as the Mantra 2.0 or the cBio Cancer genomics portal that integrates gene expression information, genomic alterations, cancer survival analysis and antibody-based pathway assays from more than 20 different cancer types and 1000 cellular models [24,58]. The European SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing 1) including the ToxBank consortium (www.toxbank.net) has created a cross-cluster data warehouse to facilitate storage and analysis of all data generated by the more than 70 research groups that form the SEURAT-1 cluster [28,53]. The data warehouse uses the Investigation/Study/Assay (ISA) tab-delimited (TAB) format as a general purpose framework with which to collect and communicate complex metadata (i.e.…”

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

“…sample characteristics, technologies used, type of measurements made) from experiments employing a combination of technologies [62]. Publicly available data from the ToxCast and the TG-GATEs projects are used as a benchmark [6,10,38,43,45,53]. The SEURAT-1 cluster has selected reference compounds, including doxorubicin and compiled extensive information on them in a semantic mediawiki (wiki.toxbank.net) [53].…”

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

“…3A) [53,54]. Bioinformatics tools variably identify a number of key pathways at different doses ( fig.…”

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

“…Development of wellstandardized and documented bioinformatics workflows is key for integration of various omics and HTS data. Solutions to standardization of data and metadata descriptions sufficiently well for biomarker development and modelling come from implementing standardized file formats such as ISA-TAB, ontologies, for experimental factors, chemical structural and ENM descriptors, and also standard operating procedures for accurate models and classifiers of toxicity [47,53,62,66,67].…”

Section: Concluding Statementsmentioning

confidence: 99%

See 3 more Smart Citations

Cancer Biology, Toxicology and Alternative Methods Development Go Hand‐in‐Hand

Kohonen

Ceder

Smit

et al. 2014

Basic Clin Pharma Tox

Self Cite

View full text Add to dashboard Cite

Toxicological research faces the challenge of integrating knowledge from diverse fields and novel technological developments generally in the biological and medical sciences. We discuss herein the fact that the multiple facets of cancer research, including discovery related to mechanisms, treatment and diagnosis, overlap many up and coming interest areas in toxicology, including the need for improved methods and analysis tools. Common to both disciplines, in vitro and in silico methods serve as alternative investigation routes to animal studies. Knowledge on cancer development helps in understanding the relevance of chemical toxicity studies in cell models, and many bioinformatics-based cancer biomarker discovery tools are also applicable to computational toxicology. Robotics-aided, cell-based, high-throughput screening, microscale immunostaining techniques and gene expression profiling analyses are common tools in cancer research, and when sequentially combined, form a tiered approach to structured safety evaluation of thousands of environmental agents, novel chemicals or engineered nanomaterials. Comprehensive tumour data collections in databases have been translated into clinically useful data, and this concept serves as template for computer-driven evaluation of toxicity data into meaningful results. Future 'cancer research-inspired knowledge management' of toxicological data will aid the translation of basic discovery results and chemicals-and materials-testing data to information relevant to human health and environmental safety.Assessing the intrinsic toxicological properties of environmental agents is central to defining hazard within the paradigm of human risk assessment used now for decades [1]. A constantly increasing number of chemicals and engineered nanomaterials (ENMs) emphasize the need of applying novel tools and screening technologies outside of the standard, both lengthy and expensive, rodent toxicological tests traditionally used in such work [1][2][3][4][5][6][7][8][9][10][11][12][13]. Especially considered for the future innovation of novel ENMs, safety evaluations should be integrated proactively and efficiently already in the material and product development phase [9,12]. Summarized under a concept termed 'Toxicity Testing in the 21st Century' or 'Tox21', biochemical and cell-based in vitro assays coupled with bioinformatics and modelling-driven in silico assays are now considered key to transforming toxicology from a previously animal-based testing practice into a computational science built on systems biology [2,4,6,[9][10][11]13]. The resulting novel research field is variably termed 'systems toxicology', 'toxicogenomics' or 'computational toxicology' [3,4,8,14,15]. Such effort typically relies on informatics-driven and modelling-based analyses of results from several experimental systems and data-rich technologies for measuring pools of biological molecules, such as mRNAs, the overall aim being to interdependently analyse toxicity data and profiling results for understanding...

show abstract

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

“…3A) [53,54]. Bioinformatics tools variably identify a number of key pathways at different doses ( fig.…”

Section: Surveying the Landscape Of Databases For Cancer Biology And mentioning

confidence: 99%

Section: Concluding Statementsmentioning

confidence: 99%

See 2 more Smart Citations

Cancer Biology, Toxicology and Alternative Methods Development Go Hand‐in‐Hand

Kohonen

Ceder

Smit

et al. 2014

Basic Clin Pharma Tox

Self Cite

View full text Add to dashboard Cite

show abstract

“…The potential ambiguity associated with how to record different experimental variables can be illustrated by considering differences between the NanoPUZZLES ISA-TABNano [47] and ToxBank ISA-TAB templates [82,83]: (1) the NanoPUZZLES Study file template "s_InvID_InVitro.CB.xls" contains the column "Factor Value [exposure medium]" for describing the suspension medium via which a tested nanomaterial is applied to the cells in an in vitro study, whereas the ToxBank Study file template "studySample.xml" contains the column "Characteristics[vehicle]" for describing the medium used to dilute a tested compound in an in vitro, in vivo or ex vivo study; (2) the NanoPUZZLES Assay file templates treat the identity of assay controls as "Parameter Value …”

Section: Experimental Variables Captured By the Templatesmentioning

confidence: 99%

An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology

Robinson¹,

Cronin²,

Richarz³

et al. 2016

Nano Online

View full text Add to dashboard Cite

Analysis of trends in nanotoxicology data and the development of data driven models for nanotoxicity is facilitated by the reporting of data using a standardised electronic format. ISA-TAB-Nano has been proposed as such a format. However, in order to build useful datasets according to this format, a variety of issues has to be addressed.These issues include questions regarding exactly which (meta)data to report and how to report them. The current article discusses some of the challenges associated with the use of ISA-TAB-Nano and presents a set of resources designed to facilitate the manual creation of ISA-TAB-Nano datasets from the nanotoxicology literature. These resources were developed within the context of the NanoPUZZLES EU project and include data collection templates, corresponding business rules that extend the generic ISA-TAB-Nano specification as well as Python code to facilitate parsing and integration of these datasets within other nanoinformatics resources. The use of these resources is illustrated by a "Toy Dataset" presented in the Supporting Information. The strengths and weaknesses of the resources are discussed along with possible future developments.

show abstract