Proteome integral solubility alteration assay combined with multi-criteria decision-making analysis for developing adverse outcome pathways

ABSTRACT: To simplify chemical risk assessment, the adverse outcome pathway (AOP) method has arisen as a framework to predict the impact of chemical exposure on human and environmental health. The development of this predictive tool requires knowledge of the molecular interaction between chemicals and protein targets. Here, we demonstrate that the identification and selection of a target candidate to develop adverse outcome pathways can be obtained by applying high-throughput identification of chemical targets by proteome integral solubility alteration (PISA) assay, followed by selecting the priority target candidate by an analytical hierarchy process. From 8 identified protein targets for TCDD from a soluble proteome extracted from hepatocytes, we selected the priority target for developing AOPs. Our combined methodologies provide identification of a molecular initiating event, essential knowledge to link molecular interaction to impact on health. The identification of chemical targets following a systematic analysis of chemical protein interaction by proteomics increases the high-throughput and reduces the traditional bias. The target selection eliminates conflicting criteria by applying a multiple-criteria decision-making analysis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Veronica Lizano-Fallas  

LAB HEAD: Susana Cristobal

PROVIDER: PXD033056 | Pride | 2023-03-11

REPOSITORIES: Pride