Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease

Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kimberly C. Paul [verfasserIn] Beate Ritz [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate

Übergeordnetes Werk:	In: Environment International - Elsevier, 2019, 170(2022), Seite 107613-
Übergeordnetes Werk:	volume:170 ; year:2022 ; pages:107613-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.envint.2022.107613

Katalog-ID:	DOAJ083776311

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allfields	10.1016/j.envint.2022.107613 doi (DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6 DE-627 ger DE-627 rakwb eng GE1-350 Kimberly C. Paul verfasserin aut Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences Beate Ritz verfasserin aut In Environment International Elsevier, 2019 170(2022), Seite 107613- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:170 year:2022 pages:107613- https://doi.org/10.1016/j.envint.2022.107613 kostenfrei https://doaj.org/article/50e25edbd660490a8c6166e98e4049e6 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412022005402 kostenfrei https://doaj.org/toc/0160-4120 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 170 2022 107613-
spelling	10.1016/j.envint.2022.107613 doi (DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6 DE-627 ger DE-627 rakwb eng GE1-350 Kimberly C. Paul verfasserin aut Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences Beate Ritz verfasserin aut In Environment International Elsevier, 2019 170(2022), Seite 107613- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:170 year:2022 pages:107613- https://doi.org/10.1016/j.envint.2022.107613 kostenfrei https://doaj.org/article/50e25edbd660490a8c6166e98e4049e6 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412022005402 kostenfrei https://doaj.org/toc/0160-4120 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 170 2022 107613-
allfields_unstemmed	10.1016/j.envint.2022.107613 doi (DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6 DE-627 ger DE-627 rakwb eng GE1-350 Kimberly C. Paul verfasserin aut Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences Beate Ritz verfasserin aut In Environment International Elsevier, 2019 170(2022), Seite 107613- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:170 year:2022 pages:107613- https://doi.org/10.1016/j.envint.2022.107613 kostenfrei https://doaj.org/article/50e25edbd660490a8c6166e98e4049e6 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412022005402 kostenfrei https://doaj.org/toc/0160-4120 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 170 2022 107613-
allfieldsGer	10.1016/j.envint.2022.107613 doi (DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6 DE-627 ger DE-627 rakwb eng GE1-350 Kimberly C. Paul verfasserin aut Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences Beate Ritz verfasserin aut In Environment International Elsevier, 2019 170(2022), Seite 107613- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:170 year:2022 pages:107613- https://doi.org/10.1016/j.envint.2022.107613 kostenfrei https://doaj.org/article/50e25edbd660490a8c6166e98e4049e6 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412022005402 kostenfrei https://doaj.org/toc/0160-4120 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 170 2022 107613-
allfieldsSound	10.1016/j.envint.2022.107613 doi (DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6 DE-627 ger DE-627 rakwb eng GE1-350 Kimberly C. Paul verfasserin aut Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology. Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences Beate Ritz verfasserin aut In Environment International Elsevier, 2019 170(2022), Seite 107613- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:170 year:2022 pages:107613- https://doi.org/10.1016/j.envint.2022.107613 kostenfrei https://doaj.org/article/50e25edbd660490a8c6166e98e4049e6 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412022005402 kostenfrei https://doaj.org/toc/0160-4120 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 170 2022 107613-
language	English
source	In Environment International 170(2022), Seite 107613- volume:170 year:2022 pages:107613-
sourceStr	In Environment International 170(2022), Seite 107613- volume:170 year:2022 pages:107613-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate Environmental sciences
isfreeaccess_bool	true
container_title	Environment International
authorswithroles_txt_mv	Kimberly C. Paul @@aut@@ Beate Ritz @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	306580829
id	DOAJ083776311
language_de	englisch
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Paul</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. 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callnumber-first	G - Geography, Anthropology, Recreation
author	Kimberly C. Paul
spellingShingle	Kimberly C. Paul misc GE1-350 misc Parkinson's disease misc Pesticides misc Toxicogenomics misc Tox21 misc Chlorpyrifos misc Copper sulfate misc Environmental sciences Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease
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topic_title	GE1-350 Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease Parkinson's disease Pesticides Toxicogenomics Tox21 Chlorpyrifos Copper sulfate
topic	misc GE1-350 misc Parkinson's disease misc Pesticides misc Toxicogenomics misc Tox21 misc Chlorpyrifos misc Copper sulfate misc Environmental sciences
topic_unstemmed	misc GE1-350 misc Parkinson's disease misc Pesticides misc Toxicogenomics misc Tox21 misc Chlorpyrifos misc Copper sulfate misc Environmental sciences
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title	Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease
ctrlnum	(DE-627)DOAJ083776311 (DE-599)DOAJ50e25edbd660490a8c6166e98e4049e6
title_full	Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease
author_sort	Kimberly C. Paul
journal	Environment International
journalStr	Environment International
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author_browse	Kimberly C. Paul Beate Ritz
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title_sort	epidemiology meets toxicogenomics: mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and parkinson’s disease
callnumber	GE1-350
title_auth	Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease
abstract	Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology.
abstractGer	Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology.
abstract_unstemmed	Background: Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson’s disease (PD). Objectives: Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. Methods: We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Results: Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Conclusions: Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology.
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title_short	Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease
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