Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases

Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Elias Zgheib [verfasserIn] Alice Limonciel [verfasserIn] Xiaoqi Jiang [verfasserIn] Anja Wilmes [verfasserIn] Steven Wink [verfasserIn] Bob van de Water [verfasserIn] Annette Kopp-Schneider [verfasserIn] Frederic Y. Bois [verfasserIn] Paul Jennings [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	transcriptomics Nrf2 AhR ATF4 toxicity pathways toxicogenomic

Übergeordnetes Werk:	In: Frontiers in Genetics - Frontiers Media S.A., 2011, 9(2018)
Übergeordnetes Werk:	volume:9 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fgene.2018.00429

Katalog-ID:	DOAJ020389922

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allfieldsGer	10.3389/fgene.2018.00429 doi (DE-627)DOAJ020389922 (DE-599)DOAJc18d3b58a931460a896ffcf06e513c59 DE-627 ger DE-627 rakwb eng QH426-470 Elias Zgheib verfasserin aut Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway. Toxicogenomic datasets from three projects (carcinoGENOMICS, Predict-IV and TG-GATEs) obtained in various experimental conditions (in human and rat in vitro liver and kidney models and rat in vivo, with bolus administration and with repeated doses) were combined and consolidated where overlaps between datasets existed. A bioinformatic analysis was performed to refine pathways' signatures and to create chemical activation capacity scores to classify chemicals by their potency and selectivity of activation of each pathway. With some refinement such an approach may improve chemical safety classification and allow biological read across on a pathway level. transcriptomics Nrf2 AhR ATF4 toxicity pathways toxicogenomic Genetics Alice Limonciel verfasserin aut Xiaoqi Jiang verfasserin aut Anja Wilmes verfasserin aut Steven Wink verfasserin aut Bob van de Water verfasserin aut Annette Kopp-Schneider verfasserin aut Frederic Y. Bois verfasserin aut Paul Jennings verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00429 kostenfrei https://doaj.org/article/c18d3b58a931460a896ffcf06e513c59 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00429/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsSound	10.3389/fgene.2018.00429 doi (DE-627)DOAJ020389922 (DE-599)DOAJc18d3b58a931460a896ffcf06e513c59 DE-627 ger DE-627 rakwb eng QH426-470 Elias Zgheib verfasserin aut Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway. Toxicogenomic datasets from three projects (carcinoGENOMICS, Predict-IV and TG-GATEs) obtained in various experimental conditions (in human and rat in vitro liver and kidney models and rat in vivo, with bolus administration and with repeated doses) were combined and consolidated where overlaps between datasets existed. A bioinformatic analysis was performed to refine pathways' signatures and to create chemical activation capacity scores to classify chemicals by their potency and selectivity of activation of each pathway. With some refinement such an approach may improve chemical safety classification and allow biological read across on a pathway level. transcriptomics Nrf2 AhR ATF4 toxicity pathways toxicogenomic Genetics Alice Limonciel verfasserin aut Xiaoqi Jiang verfasserin aut Anja Wilmes verfasserin aut Steven Wink verfasserin aut Bob van de Water verfasserin aut Annette Kopp-Schneider verfasserin aut Frederic Y. Bois verfasserin aut Paul Jennings verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00429 kostenfrei https://doaj.org/article/c18d3b58a931460a896ffcf06e513c59 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00429/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
language	English
source	In Frontiers in Genetics 9(2018) volume:9 year:2018
sourceStr	In Frontiers in Genetics 9(2018) volume:9 year:2018
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	transcriptomics Nrf2 AhR ATF4 toxicity pathways toxicogenomic Genetics
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container_title	Frontiers in Genetics
authorswithroles_txt_mv	Elias Zgheib @@aut@@ Alice Limonciel @@aut@@ Xiaoqi Jiang @@aut@@ Anja Wilmes @@aut@@ Steven Wink @@aut@@ Bob van de Water @@aut@@ Annette Kopp-Schneider @@aut@@ Frederic Y. Bois @@aut@@ Paul Jennings @@aut@@
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callnumber-first	Q - Science
author	Elias Zgheib
spellingShingle	Elias Zgheib misc QH426-470 misc transcriptomics misc Nrf2 misc AhR misc ATF4 misc toxicity pathways misc toxicogenomic misc Genetics Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases
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topic_title	QH426-470 Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases transcriptomics Nrf2 AhR ATF4 toxicity pathways toxicogenomic
topic	misc QH426-470 misc transcriptomics misc Nrf2 misc AhR misc ATF4 misc toxicity pathways misc toxicogenomic misc Genetics
topic_unstemmed	misc QH426-470 misc transcriptomics misc Nrf2 misc AhR misc ATF4 misc toxicity pathways misc toxicogenomic misc Genetics
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title	Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases
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title_full	Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases
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author_browse	Elias Zgheib Alice Limonciel Xiaoqi Jiang Anja Wilmes Steven Wink Bob van de Water Annette Kopp-Schneider Frederic Y. Bois Paul Jennings
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title_sort	investigation of nrf2, ahr and atf4 activation in toxicogenomic databases
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title_auth	Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases
abstract	Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway. Toxicogenomic datasets from three projects (carcinoGENOMICS, Predict-IV and TG-GATEs) obtained in various experimental conditions (in human and rat in vitro liver and kidney models and rat in vivo, with bolus administration and with repeated doses) were combined and consolidated where overlaps between datasets existed. A bioinformatic analysis was performed to refine pathways' signatures and to create chemical activation capacity scores to classify chemicals by their potency and selectivity of activation of each pathway. With some refinement such an approach may improve chemical safety classification and allow biological read across on a pathway level.
abstractGer	Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway. Toxicogenomic datasets from three projects (carcinoGENOMICS, Predict-IV and TG-GATEs) obtained in various experimental conditions (in human and rat in vitro liver and kidney models and rat in vivo, with bolus administration and with repeated doses) were combined and consolidated where overlaps between datasets existed. A bioinformatic analysis was performed to refine pathways' signatures and to create chemical activation capacity scores to classify chemicals by their potency and selectivity of activation of each pathway. With some refinement such an approach may improve chemical safety classification and allow biological read across on a pathway level.
abstract_unstemmed	Toxicological responses to chemical insult are largely regulated by transcriptionally activated pathways that may be independent, correlated and partially or fully overlapping. Investigating the dynamics of the interactions between stress responsive transcription factors from toxicogenomic data and defining the signature of each of them is an additional step toward a system level understanding of perturbation driven mechanisms. To this end, we investigated the segregation of the genes belonging to the three following transcriptionally regulated pathways: the AhR pathway, the Nrf2 pathway and the ATF4 pathway. Toxicogenomic datasets from three projects (carcinoGENOMICS, Predict-IV and TG-GATEs) obtained in various experimental conditions (in human and rat in vitro liver and kidney models and rat in vivo, with bolus administration and with repeated doses) were combined and consolidated where overlaps between datasets existed. A bioinformatic analysis was performed to refine pathways' signatures and to create chemical activation capacity scores to classify chemicals by their potency and selectivity of activation of each pathway. With some refinement such an approach may improve chemical safety classification and allow biological read across on a pathway level.
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title_short	Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases
url	https://doi.org/10.3389/fgene.2018.00429 https://doaj.org/article/c18d3b58a931460a896ffcf06e513c59 https://www.frontiersin.org/article/10.3389/fgene.2018.00429/full https://doaj.org/toc/1664-8021
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Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases

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