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Published on: April 3, 2017
Systematic Review of Multi-Omics Approaches to Investigate Toxicological Effects in Macrophages
Isabel Karkossa1, Stefanie Raps1, Martin von Bergen1,2
1Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research-UFZ, 04318 Leipzig, Germany.
Abstract:
Insights into the modes of action (MoAs) of xenobiotics are of utmost importance for the definition of adverse outcome pathways (AOPs), which are essential for a mechanism-based risk assessment. A well-established strategy to reveal MoAs of xenobiotics is the use of omics. However, often an even more comprehensive approach is needed, which can be achieved using multi-omics. Since the immune system plays a central role in the defense against foreign substances and pathogens, with the innate immune system building a first barrier, we systematically reviewed multi-omics studies investigating the effects of xenobiotics on macrophages. Surprisingly, only nine publications were identified, combining proteomics with transcriptomics or metabolomics. We summarized pathways and single proteins, transcripts, or metabolites, which were described to be affected upon treatment with xenobiotics in the reviewed studies, thus revealing a broad range of effects. In summary, we show that macrophages are a relevant model system to investigate the toxicological effects induced by xenobiotics. Furthermore, the multi-omics approaches led to a more comprehensive overview compared to only one omics layer with slight advantages for combinations that complement each other directly, e.g., proteome and metabolome.
Insights
Understanding how foreign substances (xenobiotics) affect cells is key for safety assessments. Multi-omics studies on macrophages reveal diverse toxicological effects, highlighting their importance in risk assessment.
Area of Science:
- Toxicology
- Immunology
- Systems Biology
Background:
- Understanding xenobiotic modes of action (MoAs) is crucial for mechanism-based risk assessment and defining adverse outcome pathways (AOPs).
- Omics technologies are established tools for MoA elucidation, but multi-omics approaches offer a more comprehensive understanding.
- The innate immune system, particularly macrophages, plays a vital role in defending against foreign substances.
Purpose of the Study:
- To systematically review multi-omics studies investigating the effects of xenobiotics on macrophages.
- To summarize affected pathways, proteins, transcripts, and metabolites in response to xenobiotics.
- To assess the utility of macrophages and multi-omics in toxicological investigations.
Main Methods:
- Systematic literature review of multi-omics studies (proteomics combined with transcriptomics or metabolomics) on xenobiotic-treated macrophages.
- Summarization of identified pathways and molecular changes.
- Comparative analysis of single-omics versus multi-omics approaches.
Main Results:
- Only nine publications met the criteria for multi-omics studies on xenobiotics and macrophages.
- A broad range of molecular effects were identified, impacting various pathways, proteins, transcripts, and metabolites.
- Multi-omics approaches provided a more comprehensive overview of xenobiotic effects compared to single-omics.
Conclusions:
- Macrophages are a relevant model system for investigating the toxicological effects of xenobiotics.
- Multi-omics, especially complementary combinations like proteome and metabolome, offer enhanced insights into xenobiotic MoAs.
- This review underscores the value of integrated omics for robust toxicological risk assessment.
