Validation of Transcriptomics-Based In Vitro Methods.

The field of transcriptomics has expanded rapidly during the last decades. This methodology provides an exceptional framework to study not only molecular changes underlying the adverse effects of a given compound, but also to understand its Mode of Action (MoA). However, the implementation of transcriptomics-based tests within the regulatory arena is not a straightforward process. One of the major obstacles in their regulatory implementation is still the interpretation of this new class of data and the judgment of the level of confidence of these tests. A key element in the regulatory acceptance of transcriptomics-based tests is validation, which still represents a major challenge. Although important advances have been made in the development and standardisation of such tests, to date there is limited experience with their validation. Taking into account the experience acquired so far, this chapter describes those aspects that were identified as important in the validation process of transcriptomics-based tests, including the assessment of standardisation, reliability and relevance. It also critically discusses the challenges posed to validation in relation to the specific characteristics of these approaches and their application in the wider context of testing strategies.