Dataset Information

Assessing the Feasibility of In Vitro Assays in Combination with Biological Matrices to Screen for Endogenous CYP450 Phenotype Biomarkers Using an Untargeted Metabolomics Approach—A Proof of Concept Study

ABSTRACT:

Cytochrome P450 (CYP) enzymes are crucial for drug metabolism, yet inter-individual variability in their activity remains a significant clinical challenge. Current phenotyping methods are often impractical or even impossible, particularly in forensic toxicology and vulnerable populations. This proof-of-concept study investigated the feasibility of using in vitro assays with human liver microsomes (HLM) and recombinant CYP enzymes (isoenzymes), combined with untargeted metabolomics, to identify endogenous biomarkers indicative of CYP phenotype. We demonstrate that HLM and isoenzymes maintain activity in the presence of complex biological matrices (blood/plasma), enabling metabolomic profiling. Untargeted analysis revealed numerous potential biomarkers, with several showing significant correlations to enzyme activity. While identification remains the major challenge, this approach offers a promising avenue for developing accessible and efficient methods for indirect CYP phenotyping, potentially facilitating investigations in scenarios where traditional approaches are limited. This work provides a foundation for future studies focused on further developing in vitro assays and validating the proposed biomarkers as well as establishing their utility in clinical and forensic settings.

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS13325 | MetaboLights | 2025-12-12

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS13325_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS13325_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13325_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13325_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 6

Similar Datasets

Project description:The goal of this project is to understand the etiology and pathology of host-pathogen interaction using high-throughput cellular phenotyping. By combining the expertise in pathogen biology, informatics and stem cell biology across the institute, this project will use targeted genetic modification in mouse embryonic stem cells to identify functions of host genes in innate immunity. We will also explore the biology of mouse embryonic stem cells and their differentiation into immune competent cells. To this end we will generate homozygous and inducible knockout lines in mouse embryonic stem cells, which will be differentiated into immune competent cells, such as macrophages or dendritic cells. These will be subjected to a panel of immune challenge and stimulation assays to characterise the functions of the disrupted genes. To identify new functions for mammalian genes in innate immunity we will:\Generate a panel of homozygous inducible gene knockout mouse ES cell lines working from a list of ca. 80 candidate genes (MGP phenotyping and GWAS hits). \Scale up differentiation protocols for immune challenge and stimulation assays.\Benchmark in vitro differentiated ES cell models against primary immune cells from selected MGP mouse lines and eventually against human iPS cells.\Screen a panel of 30 genetically modified cell lines in immunological challenge and stimulation assays, defining phenotypes at the cellular level by high content imaging, biochemically by assaying cytokine production, and at the molecular level by transcriptome analysis.\Define novel gene functions in innate immunity through network analysis of gene expression data from all challenged cell lines.\In the longer term scale up the production and phenotyping of genetically modified cell lines (mouse or human as appropriate).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

Dataset Information

Assessing the Feasibility of In Vitro Assays in Combination with Biological Matrices to Screen for Endogenous CYP450 Phenotype Biomarkers Using an Untargeted Metabolomics Approach—A Proof of Concept Study

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets