Abstract
The mapping of the human genome and the determination of corresponding gene functions, pathways, and biological mechanisms are driving the emergence of the new research fields of toxicogenomics and systems toxicology. Many technological advances such as microarrays are enabling this paradigm shift that indicates an unprecedented advancement in the methods of understanding the expression of toxicity at the molecular level. At the National Center for Toxicological Research (NCTR) of the U.S. Food and Drug Administration, core facilities for genomic, proteomic, and metabonomic technologies have been established that use standardized experimental procedures to support centerwide toxicogenomic research. Collectively, these facilities are continuously producing an unprecedented volume of data. NCTR plans to develop a toxicoinformatics integrated system (TIS) for the purpose of fully integrating genomic, proteomic, and metabonomic data with the data in public repositories as well as conventional (Italic)in vitro(/Italic) and (Italic)in vivo(/Italic) toxicology data. The TIS will enable data curation in accordance with standard ontology and provide or interface a rich collection of tools for data analysis and knowledge mining. In this article the design, practical issues, and functions of the TIS are discussed through presenting its prototype version, ArrayTrack, for the management and analysis of DNA microarray data. ArrayTrack is logically constructed of three linked components: a) a library (LIB) that mirrors critical data in public databases; b) a database (MicroarrayDB) that stores microarray experiment information that is Minimal Information About a Microarray Experiment (MIAME) compliant; and c) tools (TOOL) that operate on experimental and public data for knowledge discovery. Using ArrayTrack, we can select an analysis method from the TOOL and apply the method to selected microarray data stored in the MicroarrayDB; the analysis results can be linked directly to gene information in the LIB.
Full Text
The Full Text of this article is available as a PDF (6.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aardema Marilyn J., MacGregor James T. Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies. Mutat Res. 2002 Jan 29;499(1):13–25. doi: 10.1016/s0027-5107(01)00292-5. [DOI] [PubMed] [Google Scholar]
- Afshari C. A., Nuwaysir E. F., Barrett J. C. Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res. 1999 Oct 1;59(19):4759–4760. [PubMed] [Google Scholar]
- Ashburner M., Ball C. A., Blake J. A., Botstein D., Butler H., Cherry J. M., Davis A. P., Dolinski K., Dwight S. S., Eppig J. T. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000 May;25(1):25–29. doi: 10.1038/75556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ball Catherine A., Sherlock Gavin, Parkinson Helen, Rocca-Sera Philippe, Brooksbank Catherine, Causton Helen C., Cavalieri Duccio, Gaasterland Terry, Hingamp Pascal, Holstege Frank. The underlying principles of scientific publication. Bioinformatics. 2002 Nov;18(11):1409–1409. doi: 10.1093/bioinformatics/18.11.1409. [DOI] [PubMed] [Google Scholar]
- Baxevanis Andreas D. The Molecular Biology Database Collection: 2003 update. Nucleic Acids Res. 2003 Jan 1;31(1):1–12. doi: 10.1093/nar/gkg120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benson Dennis A., Karsch-Mizrachi Ilene, Lipman David J., Ostell James, Wheeler David L. GenBank. Nucleic Acids Res. 2003 Jan 1;31(1):23–27. doi: 10.1093/nar/gkg057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boeckmann Brigitte, Bairoch Amos, Apweiler Rolf, Blatter Marie-Claude, Estreicher Anne, Gasteiger Elisabeth, Martin Maria J., Michoud Karine, O'Donovan Claire, Phan Isabelle. The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 2003 Jan 1;31(1):365–370. doi: 10.1093/nar/gkg095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brazma A., Hingamp P., Quackenbush J., Sherlock G., Spellman P., Stoeckert C., Aach J., Ansorge W., Ball C. A., Causton H. C. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001 Dec;29(4):365–371. doi: 10.1038/ng1201-365. [DOI] [PubMed] [Google Scholar]
- Brazma Alvis, Parkinson Helen, Sarkans Ugis, Shojatalab Mohammadreza, Vilo Jaak, Abeygunawardena Niran, Holloway Ele, Kapushesky Misha, Kemmeren Patrick, Lara Gonzalo Garcia. ArrayExpress--a public repository for microarray gene expression data at the EBI. Nucleic Acids Res. 2003 Jan 1;31(1):68–71. doi: 10.1093/nar/gkg091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edgar Ron, Domrachev Michael, Lash Alex E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002 Jan 1;30(1):207–210. doi: 10.1093/nar/30.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner-Garden M., Littlejohn T. G. A comparison of microarray databases. Brief Bioinform. 2001 May;2(2):143–158. doi: 10.1093/bib/2.2.143. [DOI] [PubMed] [Google Scholar]
- Hamadeh Hisham K., Amin Rupesh P., Paules Richard S., Afshari Cynthia A. An overview of toxicogenomics. Curr Issues Mol Biol. 2002 Apr;4(2):45–56. [PubMed] [Google Scholar]
- Kanehisa Minoru. The KEGG database. Novartis Found Symp. 2002;247:91-101; discussion 101-3, 119-28, 244-52. [PubMed] [Google Scholar]
- Marshall A., Hodgson J. DNA chips: an array of possibilities. Nat Biotechnol. 1998 Jan;16(1):27–31. doi: 10.1038/nbt0198-27. [DOI] [PubMed] [Google Scholar]
- Medlin Jennifer. Toxicogenomics research consortium sails into uncharted waters. Environ Health Perspect. 2002 Dec;110(12):A744–A746. doi: 10.1289/ehp.110-a744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nuwaysir E. F., Bittner M., Trent J., Barrett J. C., Afshari C. A. Microarrays and toxicology: the advent of toxicogenomics. Mol Carcinog. 1999 Mar;24(3):153–159. doi: 10.1002/(sici)1098-2744(199903)24:3<153::aid-mc1>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
- Ramsay G. DNA chips: state-of-the art. Nat Biotechnol. 1998 Jan;16(1):40–44. doi: 10.1038/nbt0198-40. [DOI] [PubMed] [Google Scholar]
- Schmidt Charles W. Toxicogenomics: an emerging discipline. Environ Health Perspect. 2002 Dec;110(12):A750–A755. doi: 10.1289/ehp.110-a750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spengler S. J. Techview: computers and biology. Bioinformatics in the information age. Science. 2000 Feb 18;287(5456):1221–1223. doi: 10.1126/science.287.5456.1221. [DOI] [PubMed] [Google Scholar]
- Tennant Raymond W. The National Center for Toxicogenomics: using new technologies to inform mechanistic toxicology. Environ Health Perspect. 2002 Jan;110(1):A8–10. doi: 10.1289/ehp.110-a8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tong Weida, Hong Huixiao, Fang Hong, Xie Qian, Perkins Roger. Decision forest: combining the predictions of multiple independent decision tree models. J Chem Inf Comput Sci. 2003 Mar-Apr;43(2):525–531. doi: 10.1021/ci020058s. [DOI] [PubMed] [Google Scholar]
- Ulrich Roger, Friend Stephen H. Toxicogenomics and drug discovery: will new technologies help us produce better drugs? Nat Rev Drug Discov. 2002 Jan;1(1):84–88. doi: 10.1038/nrd710. [DOI] [PubMed] [Google Scholar]