Mechanism of Action

Although generation of a validated reference compendium is sufficient for the classification of novel compounds, the marker genes identified are also a valuable resource for further characterizing the MOA of compounds and compound classes. For this purpose a detailed and comprehensive description of the genes' functions, as well as of their involvement in cellular pathways, is essential. Bioinformatics will have a major influence on improving our understanding of such diverse areas as the regulation of gene expression, protein structure determination, protein-protein interactions, and cross-species comparisons. Information about exons, introns, regulators, transcription factor binding sites, splicing variants, and SNPs can be accessed and used to enlarge the knowledge about the structure and function of genes. Protein structures and motifs, functional annotations, and information about proteinprotein interactions and protein-DNA interactions can be included in more wide-reaching analyses. Metabolite data from tissues and fluids treated with compounds provide further indication of the drug's effects on a system, and such data can be correlated with gene expression and protein expression data.

Although a comprehensive discussion of the possibilities of genomics is outside the scope of this chapter, the following section outlines a few examples of MOA studies that immediately can follow the profiling of mRNA data.

0 0

Post a comment