title: The liver pharmacological and xenobiotic gene response repertoire.
abstract: We have used a supervised classification approach to systematically mine a large microarray database derived from livers of compound-treated rats. Thirty-four distinct signatures (classifiers) for pharmacological and toxicological end points can be identified. Just 200 genes are sufficient to classify these end points. Signatures were enriched in xenobiotic and immune response genes and contain un-annotated genes, indicating that not all key genes in the liver xenobiotic responses have been characterized. Many signatures with equal classification capabilities but with no gene in common can be derived for the same phenotypic end point. The analysis of the union of all genes present in these signatures can reveal the underlying biology of that end point as illustrated here using liver fibrosis signatures. Our approach using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development.
authors: Iconix Biosciences now Entelos, Foster City, CA, USA. natsoulis@gmail.com
authors: Georges
authors: G
authors: Natsoulis
authors: Cecelia I
authors: CI
authors: Pearson
authors: Jeremy
authors: J
authors: Gollub
authors: Barrett
authors: B
authors: P Eynon
authors: Joe
authors: J
authors: Ferng
authors: Ramesh
authors: R
authors: Nair
authors: Radha
authors: R
authors: Idury
authors: May D
authors: MD
authors: Lee
authors: Mark R
authors: MR
authors: Fielden
authors: Richard J
authors: RJ
authors: Brennan
authors: Alan H
authors: AH
authors: Roter
authors: Kurt
authors: K
authors: Jarnagin
mesh_terms: D000818:Animals; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D023281:Genomics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics; D051381:Rats; D015203:Reproducibility of Results; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D015262:Xenobiotics