Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology

@article{citeulike:2996807, abstract = {The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology.}, author = {Lam, Siew H. and Mathavan, Sinnakarupan and Tong, Yan and Li, Haixia and Karuturi and Wu, Yilian and Vega, Vinsensius B. and Liu, Edison T. and Gong, Zhiyuan }, citeulike-article-id = {2996807}, doi = {http://dx.doi.org/10.1371/journal.pgen.1000121}, journal = {PLoS Genet}, keywords = {chemogenomics, cross-species, zebrafish}, month = {July}, number = {7}, pages = {e1000121+}, posted-at = {2008-07-12 21:19:12}, priority = {2}, publisher = {Public Library of Science}, title = {Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology}, url = {http://dx.doi.org/10.1371/journal.pgen.1000121}, volume = {4}, year = {2008} }

TY - JOUR ID - citeulike:2996807 L3 - citeulike-article-id:2996807 TI - Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology JF - PLoS Genet VL - 4 IS - 7 SP - e1000121 PB - Public Library of Science N2 - The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology. KW - chemogenomics KW - cross-species KW - zebrafish AU - Lam, Siew AU - Mathavan, Sinnakarupan AU - Tong, Yan AU - Li, Haixia AU - Karuturi AU - Wu, Yilian AU - Vega, Vinsensius AU - Liu, Edison AU - Gong, Zhiyuan PY - 2008/07/11/ UR - http://dx.doi.org/10.1371/journal.pgen.1000121 ER -