The Comparative Toxicogenomics Database (CTD): a resource for comparative toxicological studies

Mattingly, Carolyn J.; Rosenstein, MC; Colby, Glenn T.; Forrest, Jr Jn; Jl, Boyer

doi:10.1002/jez.a.307

Cited by 134 publications

(110 citation statements)

References 12 publications

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“…This cell line from a cartilaginous fish provides a means to study the cell biology, physiology, and genomics of Chondrichthyes. Recently, the National Human Genome Research Institute targeted for comprehensive genomic sequencing Leucoraja erinacia, an elasmobranch of the superorder Squaliformes, related to S. acanthias, underscoring the value of Chondrichthyes for comparative biology (6) In efforts to explore the cell biology and genomics of cartilaginous fish, we used the SAE shark cell line to prepare a normalized cDNA library primed from the 3Ј end of the mRNA. A database of Ͼ5,000 EST sequences representative of gene expression in the cell line was generated by sequencing from the 5Ј end of the ESTs.…”

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confidence: 99%

RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

Forest

Nishikawa

Kobayashi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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We have established a cartilaginous fish cell line [Squalus acanthias embryo cell line (SAE)], a mesenchymal stem cell line derived from the embryo of an elasmobranch, the spiny dogfish shark S. acanthias. Elasmobranchs (sharks and rays) first appeared >400 million years ago, and existing species provide useful models for comparative vertebrate cell biology, physiology, and genomics. Comparative vertebrate genomics among evolutionarily distant organisms can provide sequence conservation information that facilitates identification of critical coding and noncoding regions. Although these genomic analyses are informative, experimental verification of functions of genomic sequences depends heavily on cell culture approaches. Using ESTs defining mRNAs derived from the SAE cell line, we identified lengthy and highly conserved gene-specific nucleotide sequences in the noncoding 3 UTRs of eight genes involved in the regulation of cell growth and proliferation. Conserved noncoding 3 mRNA regions detected by using the shark nucleotide sequences as a starting point were found in a range of other vertebrate orders, including bony fish, birds, amphibians, and mammals. Nucleotide identity of shark and human in these regions was remarkably well conserved. Our results indicate that highly conserved gene sequences dating from the appearance of jawed vertebrates and representing potential cis-regulatory elements can be identified through the use of cartilaginous fish as a baseline. Because the expression of genes in the SAE cell line was prerequisite for their identification, this cartilaginous fish culture system also provides a physiologically valid tool to test functional hypotheses on the role of these ancient conserved sequences in comparative cell biology.noncoding sequence ͉ sequence conservation ͉ Squalus acanthias E fforts toward a comprehensive compilation of cell biological, physiological, and genomic information from a variety of vertebrate species are providing a rich source of comparative data representing critical points in evolutionary divergence (1). Although available information is rapidly expanding for teleosts (bony fishes; ref.2), few cell biological or genomic data are available for the most primitive jawed vertebrates, the cartilaginous fish, class Chondrichthyes, largely represented by the order Elasmobranchii (3, 4). This information would extend comparative data through Ͼ450 million years of evolution. We have derived an embryonic mesenchymal stem cell line [Squalus acanthias embryo cell line (SAE)] from the elasmobranch S. acanthias, the spiny dogfish shark (5). This cell line from a cartilaginous fish provides a means to study the cell biology, physiology, and genomics of Chondrichthyes. Recently, the National Human Genome Research Institute targeted for comprehensive genomic sequencing Leucoraja erinacia, an elasmobranch of the superorder Squaliformes, related to S. acanthias, underscoring the value of Chondrichthyes for comparative biology (6) In efforts to explore the cell biology and genomics of c...

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mentioning

confidence: 99%

RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

Forest

Nishikawa

Kobayashi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, the figure below shows an implementation of ODIN customized for curation of the Comparative Toxicogenomics Database (CTD, Mattingly et al, 2006). The left panel shows…”

Section: Resultsmentioning

confidence: 99%

EMBnet.journal 18 Suppl. B

journal¹

2012

EMBnet j.

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“…Toxicogenomics has provided valuable mechanistic insight into various adverse drug reactions and has been reviewed with a focus on hepatotoxicity and nephrotoxicity (Kienhuis et al 2011). With the development of toxicogenomics, many toxicogenomics databases have been created, such as Connectivity map (CMap) (Lamb et al 2006), the Genomics-Assisted Toxicity Evaluation System (TGGATEs) (Uehara et al 2010), and the Comparative Toxicogenomics Database (CTD) (Davis et al 2013;Mattingly et al 2006). These databases provide insight into complex chemical-gene and protein interaction networks and improve our understanding of the toxicity mechanisms.…”

Section: Systems Toxicologymentioning

confidence: 99%

In silicoADME/T modelling for rational drug design

Wang

Xing

Yue

et al. 2015

Quart. Rev. Biophys.

280

155

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Abstract. In recent decades, in silico absorption, distribution, metabolism, excretion (ADME), and toxicity (T) modelling as a tool for rational drug design has received considerable attention from pharmaceutical scientists, and various ADME/T-related prediction models have been reported. The high-throughput and low-cost nature of these models permits a more streamlined drug development process in which the identification of hits or their structural optimization can be guided based on a parallel investigation of bioavailability and safety, along with activity. However, the effectiveness of these tools is highly dependent on their capacity to cope with needs at different stages, e.g. their use in candidate selection has been limited due to their lack of the required predictability. For some events or endpoints involving more complex mechanisms, the current in silico approaches still need further improvement. In this review, we will briefly introduce the development of in silico models for some physicochemical parameters, ADME properties and toxicity evaluation, with an emphasis on the modelling approaches thereof, their application in drug discovery, and the potential merits or deficiencies of these models. Finally, the outlook for future ADME/T modelling based on big data analysis and systems sciences will be discussed.

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The Comparative Toxicogenomics Database (CTD): a resource for comparative toxicological studies

Cited by 134 publications

References 12 publications

RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

EMBnet.journal 18 Suppl. B

In silicoADME/T modelling for rational drug design

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