Toxicity mechanisms identification via gene set enrichment analysis of time-series toxicogenomics data: impact of time and concentration

Environmental Science & Technology
Ce GaoApril Z Gu

Abstract

The advance in high-throughput "toxicogenomics" technologies, which allows for concurrent monitoring of cellular responses globally upon exposure to chemical toxicants, presents promises for next-generation toxicity assessment. It is recognized that cellular responses to toxicants have a highly dynamic nature, and exhibit both temporal complexity and dose-response shifts. Most current gene enrichment or pathway analysis lack the recognition of the inherent correlation within time series data, and may potentially miss important pathways or yield biased and inconsistent results that ignore dynamic patterns and time-sensitivity. In this study, we investigated the application of two score metrics for GSEA (gene set enrichment analysis) to rank the genes that consider the temporal gene expression profile. One applies a novel time series CPCA (common principal components analysis) to generate scores for genes based on their contributions to the common temporal variation among treatments for a given chemical at different concentrations. Another one employs an integrated altered gene expression quantifier-TELI (transcriptional effect level index) that integrates altered gene expression magnitude over the exposure time. By comparing the...Continue Reading

References

Dec 1, 1981·Environmental Health Perspectives·B Altshuler
Jul 21, 2000·Pacific Symposium on Biocomputing·S RaychaudhuriR B Altman
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·T K Van DykR A LaRossa
Jun 8, 2001·Bioinformatics·J Aach, G M Church
May 8, 2004·Bioinformatics·Ziv Bar-Joseph
Mar 22, 2005·Chemical Research in Toxicology·Kevin R Hayes, Christopher A Bradfield
May 11, 2005·Nature Reviews. Genetics·Mads KaernJames J Collins
Sep 2, 2005·Nature·Steve E CalvanoUNKNOWN Inflamm and Host Response to Injury Large Scale Collab. Res. Program
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Oct 19, 2006·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Alexander SchliepAlexander Schönhuth
Jan 15, 2008·Toxicology and Applied Pharmacology·Gene J AhlbornDon A Delker
Apr 29, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lyle D Burgoon, Timothy R Zacharewski
May 24, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Melvin E AndersenRussell S Thomas
Jul 1, 2008·Bioinformatics·Tien-ho LinZiv Bar-Joseph
Aug 8, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·George P Daston
Feb 6, 2009·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Gal Chechik, Daphne Koller
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dmitry NevozhayGábor Balázsi
Jul 17, 2009·Environmental Science & Technology·Annalisa Onnis-HaydenApril Z Guc
Jun 25, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Daniel KrewskiLauren Zeise
Mar 19, 2011·Cell·Nir Yosef, Aviv Regev
Apr 14, 2011·Radiation Research·Alexandre Mezentsev, Sally A Amundson
May 27, 2011·Environmental Science & Technology·Na Gou, April Z Gu
Dec 20, 2011·Current Opinion in Biotechnology·Sahar MelamedShimshon Belkin
Mar 3, 2012·PLoS Computational Biology·Purvesh KhatriAtul J Butte
Jun 19, 2012·Environmental Science & Technology·Ce GaoApril Z Gu
Jul 19, 2012·Nature Reviews. Genetics·Ziv Bar-JosephItamar Simon
Nov 3, 2012·Interdisciplinary Toxicology·Gagan FloraArchana Tiwari
Nov 13, 2012·Nucleic Acids Research·Ingrid M KeselerPeter D Karp

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Citations

Feb 10, 2017·PLoS Computational Biology·Tracey M FilzenMatthew Tudor
Mar 3, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Dalinda Isabel Sánchez-VidañaMan-Sau Wong
Nov 3, 2016·Alternatives to Laboratory Animals : ATLA·Jenny McCann, Terry McCann
Jul 7, 2018·Environmental Science & Technology·Thomas H HamptonJoseph R Shaw

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