Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets
The impact of exposure to multiple chemicals raises concerns for human and environmental health. The adverse outcome pathway method offers a framework to support mechanism-based assessment in environmental health starting by describing which mechanisms are triggered upon interaction with different s...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/11/2/189 |
| _version_ | 1797618029611188224 |
|---|---|
| author | Veronica Lizano-Fallas Ana Carrasco del Amor Susana Cristobal |
| author_facet | Veronica Lizano-Fallas Ana Carrasco del Amor Susana Cristobal |
| author_sort | Veronica Lizano-Fallas |
| collection | DOAJ |
| description | The impact of exposure to multiple chemicals raises concerns for human and environmental health. The adverse outcome pathway method offers a framework to support mechanism-based assessment in environmental health starting by describing which mechanisms are triggered upon interaction with different stressors. The identification of the molecular initiating event and the molecular interaction between a chemical and a protein target is still a challenge for the development of adverse outcome pathways. The cellular response to chemical exposure studied with omics could not directly identify the protein targets. However, recent mass spectrometry-based methods are offering a proteome-wide identification of protein targets interacting with s but unrevealing a molecular initiating event from a set of targets is still dependent on available knowledge. Here, we directly coupled the target identification findings from the proteome integral solubility alteration assay with an analytical hierarchy process for the prediction of a prioritized molecular initiating event. We demonstrate the applicability of this combination of methodologies with a test compound (TCDD), and it could be further studied and integrated into AOPs. From the eight protein targets identified by the proteome integral solubility alteration assay after analyzing 2824 human hepatic proteins, the analytical hierarchy process can select the most suitable protein for an AOP. Our combined method solves the missing links between high-throughput target identification and prediction of the molecular initiating event. We anticipate its utility to decipher new molecular initiating events and support more sustainable methodologies to gain time and resources in chemical assessment. |
| first_indexed | 2024-03-11T08:04:27Z |
| format | Article |
| id | doaj.art-fec9cbb613874171b28f1bb86fd897b1 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T08:04:27Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-fec9cbb613874171b28f1bb86fd897b12023-11-16T23:38:10ZengMDPI AGToxics2305-63042023-02-0111218910.3390/toxics11020189Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical TargetsVeronica Lizano-Fallas0Ana Carrasco del Amor1Susana Cristobal2Department of Biomedical and Clinical Sciences, Cell Biology, Faculty of Medicine, Linköping University, 581 85 Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Cell Biology, Faculty of Medicine, Linköping University, 581 85 Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Cell Biology, Faculty of Medicine, Linköping University, 581 85 Linköping, SwedenThe impact of exposure to multiple chemicals raises concerns for human and environmental health. The adverse outcome pathway method offers a framework to support mechanism-based assessment in environmental health starting by describing which mechanisms are triggered upon interaction with different stressors. The identification of the molecular initiating event and the molecular interaction between a chemical and a protein target is still a challenge for the development of adverse outcome pathways. The cellular response to chemical exposure studied with omics could not directly identify the protein targets. However, recent mass spectrometry-based methods are offering a proteome-wide identification of protein targets interacting with s but unrevealing a molecular initiating event from a set of targets is still dependent on available knowledge. Here, we directly coupled the target identification findings from the proteome integral solubility alteration assay with an analytical hierarchy process for the prediction of a prioritized molecular initiating event. We demonstrate the applicability of this combination of methodologies with a test compound (TCDD), and it could be further studied and integrated into AOPs. From the eight protein targets identified by the proteome integral solubility alteration assay after analyzing 2824 human hepatic proteins, the analytical hierarchy process can select the most suitable protein for an AOP. Our combined method solves the missing links between high-throughput target identification and prediction of the molecular initiating event. We anticipate its utility to decipher new molecular initiating events and support more sustainable methodologies to gain time and resources in chemical assessment.https://www.mdpi.com/2305-6304/11/2/189molecular initiating eventadverse outcome pathwaychemical targetproteome integral solubility alteration assaythermal proteome profilingpredictive toxicology |
| spellingShingle | Veronica Lizano-Fallas Ana Carrasco del Amor Susana Cristobal Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets Toxics molecular initiating event adverse outcome pathway chemical target proteome integral solubility alteration assay thermal proteome profiling predictive toxicology |
| title | Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets |
| title_full | Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets |
| title_fullStr | Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets |
| title_full_unstemmed | Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets |
| title_short | Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets |
| title_sort | prediction of molecular initiating events for adverse outcome pathways using high throughput identification of chemical targets |
| topic | molecular initiating event adverse outcome pathway chemical target proteome integral solubility alteration assay thermal proteome profiling predictive toxicology |
| url | https://www.mdpi.com/2305-6304/11/2/189 |
| work_keys_str_mv | AT veronicalizanofallas predictionofmolecularinitiatingeventsforadverseoutcomepathwaysusinghighthroughputidentificationofchemicaltargets AT anacarrascodelamor predictionofmolecularinitiatingeventsforadverseoutcomepathwaysusinghighthroughputidentificationofchemicaltargets AT susanacristobal predictionofmolecularinitiatingeventsforadverseoutcomepathwaysusinghighthroughputidentificationofchemicaltargets |