BOX 9-1

Validation of Toxicogenomic Applications

  1. Platform validation: Does the particular technology provide reproducible and reliable measurements?

  2. Software/data analysis validation: Is the software used for analysis of a particular experimental design appropriate and does it provide insight into the biology of the problem under study?

  3. Biologic validation: Are the results from an “-omics” analysis consistent with the biology or can they be verified by another focused approach such as quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for microarrays or enzyme-linked immunosorbent assay (ELISA)1 for proteomics?

  4. Generalizability: Can the results of a particular analysis be extended from the test samples to the broader population or from animal models to humans?

  5. Regulatory validation: Is a particular assay or test suitable for use in evaluating the safety and efficacy of new compounds or in diagnostic or prognostic applications?

It is important to recognize that validation is an iterative process, so that, for example, the biologic validation step can refine platform and software validation and help direct efforts to generalize the results.

Platform Validation

Any toxicogenomic study is predicated on the assumption that the technologies provide accurate and relevant measures of the biologic processes underlying what is being assayed. For transcriptomic profiles with microarrays, for which we have the most data, there have been many successful applications, often with high rates of validation using an alternative technology such as Northern analysis or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR); however, it should be noted that each of these techniques has experimental biases. The issue of concordance between different microarray platforms was discussed in Chapter 2. However, recent reports suggest that adherence to good, standard laboratory practices and careful analysis of data can lead to high-quality, reproducible results in which the biology of the system under study drives the gene expression profiles that are observed (Bammler et al. 2005; Dobbin et al. 2005; Irizarry et al. 2005; Larkin et al. 2005). Similar efforts


ELISA is a quantitative in vitro test for an antibody or antigen in which the test material is adsorbed on a surface and exposed to either a complex of an enzyme linked to an antibody specific for the antigen or an enzyme linked to an anti-immunoglobulin specific for the antibody followed by reaction of the enzyme with a substrate to yield a colored product corresponding to the concentration of the test material. (Merriam-Webster’s Medical Dictionary, Immunosorbent Assay, [Accessed: April 12, 2007]).

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