Toxygates: interactive toxicity analysis on a hybrid microarray and linked data platform

Nyström-Persson, Johan; Igarashi, Yoshinobu; Ito, Maori; Morita, Mizuki; Nakatsu, Noriyuki; Yamada, Hiroshi; Mizuguchi, Kenji

doi:10.1093/bioinformatics/btt531

Cited by 30 publications

(40 citation statements)

References 31 publications

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“…The Mode of Action by NeTwoRk Analysis Mantra 2.0 database has clustered the CMap database and annotated the MoA of each compound, enabling determination of an unknown compound's MoA by referring to the neighbouring compounds in the network [58]. Connectivity mapping has been implemented for the TGGATEs data set in the liver toxicity map service; the Toxygates interface to the TG-GATEs data also enables ranking of compounds based on the genes that they regulate [54,57].…”

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%

“…Connectivity mapping with gene expression or HTS data is an example of data-driven activity [10,13,44,54,57]. Differently, the identification of molecular initiating events and key events that lead to an adverse outcome is a concept-driven activity that facilitates evaluation of evidence for toxicity [12,13,31,32,64].…”

Section: Concluding Statementsmentioning

confidence: 99%

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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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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%

See 1 more Smart Citation

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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“…When Open TG-GATEs had originally been released, it was necessary to perform substantial pre-processing before any investigation could commence. To lower the barrier to entry for new investigators, we developed Toxygates 6 (http://toxygates.nibiohn.go.jp), the first version of which was made publicly available in 2013. At that time, the main achievement was to allow anybody who was interested to select samples quickly (e.g., compounds, exposure times) and look at expression data, visualise time or dose series, and show their annotations such as Gene Ontology (GO) terms 7 or KEGG pathways 8 .…”

Section: Introductionmentioning

confidence: 99%

Interactive Toxicogenomics: Gene set discovery, clustering and analysis in Toxygates

Nyström-Persson

Natsume-Kitatani

Igarashi

et al. 2017

Sci Rep

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Toxygates was originally released as a user-friendly interface to enhance the accessibility of the large-scale toxicogenomics database, Open TG-GATEs, generated by the Japanese Toxicogenomics Project. Since the original release, significant new functionality has been added to enable users to perform sophisticated computational analysis with only modest bioinformatics skills. The new features include an orthologous mode for data comparison among different species, interactive clustering and heatmap visualisation, enrichment analysis of gene sets, and user data uploading. In a case study, we use these new functions to study the hepatotoxicity of peroxisome proliferator-activated receptor alpha (PPARα) agonist WY-14643. Our findings suggest that WY-14643 caused hypertrophy in the bile duct by intracellular Ca2+ dysregulation, which resulted in the induction of genes in a non-canonical WNT/Ca2+ signalling pathway. With this new release of Toxygates, we provide a suite of tools that allow anyone to carry out in-depth analysis of toxicogenomics in Open TG-GATEs, and of any other dataset that is uploaded.

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“…Toxygates was originally developed for this purpose, which enables to display the gene expression intensity values obtained by selected compounds and experimental conditions for genes of interest [6]. …”

Section: Introductionmentioning

confidence: 99%

Integrated toxicogenomics analysis with Toxygates for inferring molecular mechanisms

Natsume-Kitatani

Nyström-Persson

Igarashi

et al. 2017

Genomics Comput Biol

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Assessment of the safety of drug candidates in early research and development (R&D) stage holds the key to the successful drug development. Toxicogenomics is one of the promising approaches using omics techniques since a number of ‘omics databases is rapidly growing. Although many of these databases are open to the public, there remain some barriers for biologists regardless of their bioinformatics skills. Toxygates was originally developed as a user-friendly interface for Open TG-GATEs, which is one of the largest and most widely used toxicogenomics databases. Since the original Toxygates was developed to enable users to display the gene expression values obtained by selected compounds or experimental conditions for genes of interest, there were some limitations as an analytical platform. To overcome this situation, significant improvements have been added and finally, a new version of Toxygates allows users to analyze the data such as creating heatmap for visualization of gene expression profile, performing hierarchical clustering and creating a dendrogram with interactive display, performing several types of enrichment analysis such as gene ontology and pathways and uploading user data for further analysis. As a case study, we used Toxygates to successfully find novel insights that the hepatotoxicity caused by well-studied PPARα agonist WY-14643 may include the disruption of intracellular calcium dynamics and imbalance between PPARα signaling and Wnt signaling.

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Toxygates: interactive toxicity analysis on a hybrid microarray and linked data platform

Cited by 30 publications

References 31 publications

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

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

Interactive Toxicogenomics: Gene set discovery, clustering and analysis in Toxygates

Integrated toxicogenomics analysis with Toxygates for inferring molecular mechanisms

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