"Molecular Fingerprinting": Characterization of Biological Effects by Patterns of Perturbations in Cellular Levels of Macro and Small Molecules
An important aspect of the ability to monitor patterns of perturbations in key pathways through global analysis of cellular levels of molecular components is the ability to develop "fingerprints" of cellular responses to classes of chemicals with known common biological effects (e.g., Hamadeh et al., 2002; Robertson et al., 2000; Murata et al., 1999). Such fingerprints have the potential: (1) to allow classification of chemicals based on the biological responses they elicit, (2) to provide mechanistic information about the cellular perturbations and responses elicited by specific exposures (through comparison with responses associated with previously characterized mechanisms), and (3) to identify biomarkers specific to particular classes of molecular damage.
It should become possible to develop a compendium of chemical class-specific cellular perturbations, and to introduce a new system of biological classification of chemicals based on similarities in their mechanisms of interaction with key cell receptors and response elements (Hughes et al., 2000). Such a classification would have several practical applications. In product development, for example, the biological fingerprints of new candidates for development could be compared with previously characterized agents with known beneficial or detrimental properties. Complex mixtures, such as environmental samples or product impurities, could be analyzed to determine if they produce patterns that indicate adverse biological effects—and the patterns observed would provide valuable mechanistic information about the nature of the expected effects as well as the chemical class likely to be associated with a particular pattern. Such fingerprints would also predict particular mechanisms of action, guiding subsequent studies designed to provide confirmatory evidence. This ability to predict mechanism based on "fingerprints" of biomarker and pathway responses, and to categorize chemicals based on patterns of effect produced by well-characterized agents, should facilitate selection of agents for product development and greatly increase the efficiency of toxicology testing strategies (e.g., Ulrich and Friend, 2002).