@article{2fedd01700e84337b8702995fe2732a6,
title = "Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses",
abstract = "Gene expression profiling is a widely used technique with data from the majority of published microarray studies being publicly available. These data are being used for meta-analyses and in silico discovery; however, the comparability of toxicogenomic data generated in multiple laboratories has not been critically evaluated. Using the power of prospective multilaboratory investigations, seven centers individually conducted a common toxicogenomics experiment designed to advance understanding of molecular pathways perturbed in liver by an acute toxic dose of N-acetyl-p-aminophenol (APAP) and to uncover reproducible genomic signatures of APAP-induced toxicity. The nonhepatotoxic APAP isomer N-acetyl-m-aminophenol was used to identify gene expression changes unique to APAP. Our data show that c-Myc is induced by APAP and that c-Myc-centered interactomes are the most significant networks of proteins associated with liver injury. Furthermore, sources of error and data variability among Centers and methods to accommodate this variability were identified by coupling gene expression with extensive toxicological evaluation of the toxic responses. We show that phenotypic anchoring of gene expression data is required for biologically meaningful analysis of toxicogenomic experiments.",
keywords = "Liver injury, Phenotypic anchoring, Toxicogenomics",
author = "Beyer, {Richard P.} and Fry, {Rebecca C.} and Lasarev, {Michael R.} and McConnachie, {Lisa A.} and Meira, {Lisiane B.} and Palmer, {Valerie S.} and Powell, {Christine L.} and Ross, {Pamela K.} and Bammler, {Theo K.} and Bradford, {Blair U.} and Cranson, {Alex B.} and Cunningham, {Michael L.} and Fannin, {Rickie D.} and Higgins, {Gregory M.} and Patrick Hurban and Kayton, {Robert J.} and Kerr, {Kathleen F.} and Oksana Kosyk and Lobenhofer, {Edward K.} and Sieber, {Stella O.} and Vliet, {Portia A.} and Weis, {Brenda K.} and Russel Wolfinger and Woods, {Courtney G.} and Freedman, {Jonathan H.} and Elwood Linney and Kaufmann, {William K.} and Kavanagh, {Terrance J.} and Paules, {Richard S.} and Ivan Rusyn and Samson, {Leona D.} and Spencer, {Peter S.} and William Suk and Tennant, {Raymond J.} and Helmut Zarbl",
note = "Funding Information: The authors wish to thank David Schwartz (NIEHS) for contributing to the study design. The members of the Toxicogenomics Research Consortium also acknowledge the efforts of David Balshaw and Michael Humble of the NIEHS, and support of Molly Vallant of the NTP and the technical assistance of Laurene Fomby, Tammy Wheat, Daphne Vasconcelos, Michael Ryan, Brian Burback, and Milton Hejtacik (all from Battelle), and the Investigation Genomics Group of Cogenics. This work was supported (in part) by the Intramural Research Program of the National Institutes of Health and NIEHS.",
year = "2007",
month = sep,
doi = "10.1093/toxsci/kfm150",
language = "English (US)",
volume = "99",
pages = "326--337",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "1",
}