The Japanese toxicogenomics project: Application of toxicogenomics

Uehara, Takeki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

doi:10.1002/mnfr.200900169

Cited by 178 publications

(172 citation statements)

References 35 publications

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“…From a total of three tests an average IC 10 value of 18 mM was calculated. The subcytotoxic concentration of APAP used in hHEP was 5 mM, which corresponds to the value previously described [42]. PCA of the microarray data shows highly reproducible results for the in vitro samples (Fig.…”

Section: Predictive Capacity Of Hskp-hpc For Apap-induced Hepatotoxicitysupporting

confidence: 73%

“…Microarray data of human hepatocyte cultures (hHEP) established from human cryopreserved hepatocytes were obtained from the toxicology database TG-GATEs. The latter being established by a 5-year collaboration between the National Institute of Health Sciences and 17 pharmaceutical companies in Japan [41,42]. Only data from cells exposed for 24 h to 5 mM APAP and the respective vehicle controls was used for comparative gene expression analysis with self obtained data.…”

Section: Microarray Data Analysismentioning

confidence: 99%

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Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

et al. 2015

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Section: Predictive Capacity Of Hskp-hpc For Apap-induced Hepatotoxicitysupporting

confidence: 73%

Section: Microarray Data Analysismentioning

confidence: 99%

Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

et al. 2015

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“…[37] Terms in grey have a significance, after multiple testing correction, below adjP < 0.05 (Supporting Information SI Table 6). B) The gene dao (D-amino-acid oxidase) is associated with a number of the gold compounds according to the Comparative Toxicogenomics Database (CTD), sorted by frequency of chemical-gene associations.…”

Section: Discussionmentioning

confidence: 99%

“…[36] Recently this situation has been addressed by the release of two such datasets: the TGP (TG-GATEs) dataset [37] and the DrugMatrix. [38] Both have a uniform experimental design, assess a large number of marketed drugs alongside standard toxicological model compounds (such as acetaminophen) and provide in vitro as well as in vivo data for comparative analysis.…”

Section: Public Datamentioning

confidence: 99%

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

Kohonen

Benfenati

Bower

et al. 2013

Molecular Informatics

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The aim of the SEURAT‐1 (Safety Evaluation Ultimately Replacing Animal Testing‐1) research cluster, comprised of seven EU FP7 Health projects co‐financed by Cosmetics Europe, is to generate a proof‐of‐concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT‐1 strategy is to adopt a mode‐of‐action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross‐cluster infrastructure project whose activities include the development of a data warehouse to provide a web‐accessible shared repository of research data and protocols, a physical compounds repository, reference or “gold compounds” for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA‐Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds.

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“…Reduced sets of toxicity associated genes can be assayed at higher throughput or lower cost, for example with Luminex â technology [36,37]. Microarrays, such as Affymetrix GeneChips â , form currently the basis for most of the existing gene profiling data, including the 'Japanese Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system' (TG-GATEs) reference database [15,25,38]. Pathway activation can be studied using open source tools or commercial tools, such as the Ingenuity Pathway Analysis (Ingenuity â Systems, www.ingenuity.com) or the freely available InCroMap tool [39,40].…”

Section: From Hts Of Many Agents To Genomic Profiling Analysis Of Thementioning

confidence: 99%

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

Kohonen

Ceder

Smit

et al. 2014

Basic Clin Pharma Tox

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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...

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The Japanese toxicogenomics project: Application of toxicogenomics

Cited by 178 publications

References 35 publications

Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

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

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

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