Chemogenomics, application of genomic tools in pharmacology and toxicology, offers a promising approach that will enhance drug discovery (target identification/validation, lead identification, efficacy evaluation) and toxicity assessment 
. Presently, invertebrates such as the worm Caenorhabditis elegans
and fly Drosophila melanogaster
, are the only animal models that have benefited from whole-adult-organism expression chemogenomics 
. The benefits of whole-adult-organism chemogenomics would usually translate into large-scale, high-throughput, high-content and cost-effective applications for chemical biology. It is highly desirable that the benefits of whole-adult-organism chemogenomics can be realized in a vertebrate model because of the many biological processes, health risks and diseases that are restricted to a mature vertebrate system including humans. The existing cell-, fly- and worm-based models, while suited for high-throughput chemogenomics, lacked the relevant physiological whole-organism setting of an adult vertebrate. This is especially important in the context of pharmacology and toxicology when many of the potentially targeted organ-systems such as the endocrine, digestive (liver in particular), immune, muscular-skeletal, vasculature, kidney are absent from the existing high-throughput models. In contrast, the rodent models, though providing in vivo
adult vertebrate data, are not suited for high-throughput applications and are not cost-effective 
, thus creating a bottleneck situation when in vivo
biological data, especially toxicology, is required for the high number of ‘hits’ generated from in vitro
screenings or for the many newly emerging industrial compounds and waste that are coming into contact with the public and environment. We propose that whole-adult chemogenomics performed on a small vertebrate such as the zebrafish would be a strategy that is sufficiently high-throughput, cost-effective and would generate high content in vivo
vertebrate data potentially useful for large-scale screening and toxicity testing purposes.
Conceptually, whole-adult-organism expression chemogenomics would capture the sum-total of the transcriptomic changes in an entire adult organism as a single biological entity responding to exogenous chemical cues. This, however, would have its inherent limitations such as loss of weak signals or signals from smaller tissues and loss of specific location of response, and they may be compounded further by the greater biological complexity in vertebrates compared to invertebrates. Thus, while whole-adult-organism chemogenomics had been shown to be useful in invertebrate models with regard to compound screening 
and identifying biological processes affected by specific compounds 
, it is not known if chemogenomics data generated from a whole adult vertebrate will be useful. We hypothesized that since strong and well-represented expression signals are likely to be detected in whole-adult-organism chemogenomics, the expression signals that are captured would be robust for predictive chemical biology and for uncovering biology that is widely associated with the chemical-induced responses/effects in the adult vertebrate.
However, the idea of performing high-throughput whole-adult-organism chemogenomics on a vertebrate model was practically not feasible, if not unimaginable, until microarray technology was made available to small aquarium fish such as the zebrafish. The availability of the zebrafish in large numbers, its small size, low husbandry cost, vast genomic resources and its present use in disease modeling 
and drug screening 
, make the zebrafish ideal for high-throughput whole-adult-organism chemogenomics. Moreover, owing to their close physiological relationship with the environment, fish are highly sensitive to environmental changes particularly exogenous chemical cues; therefore the impact of chemical effects on fish system is more easily defined and readily studied than on terrestrial species 
. Previously, we and others have shown that zebrafish responded biologically to chemicals, such as small molecules, drugs and environmental toxicants, in a similar manner as mammals 
. In this study, we chose P(H)AHs [represented by Benzo[a]pyrene (BAP), 3-Methylcholanthrene (MC), 2,3,7,8-Tetrachlorodibenzodioxin (TCDD)] and ECs [represented by 17-beta estradiol (Es), Diethylstilbestrol (DES), Bisphenol A (Bis)] as model compounds because they represent two classes of chemicals with wide implications to human health. Both P(H)AHs and ECs are potent AHR and ER agonists, respectively, and these receptors are known to cross-talk and they are regulators of important cellular functions that are involved in various biological processes and have been associated with several patho-physiological conditions 
. Some of these compounds have been used as drugs or investigated for therapeutic potential 
. Moreover, both classes of compounds are also environmental carcinogens and endocrine disruptors that have generated considerable public health concern 
. By focusing on P(H)AHs and ECs in this study, we performed chemogenomics on whole adult zebrafish and demonstrated that it is good for large-scale predictive chemical biology, for discovering biomarkers and major signaling pathways, as well as useful for human health risk and biological insight inference. Our study placed zebrafish in a strategic position to bridge the gap between in vitro
cell-based model and in vivo
rodent model in chemogenomics.