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Trends in Pharmacological Sciences Feb 2019Toxicogenomics (TGx) has contributed significantly to toxicology and now has great potential to support moves towards animal-free approaches in regulatory decision... (Review)
Review
Toxicogenomics (TGx) has contributed significantly to toxicology and now has great potential to support moves towards animal-free approaches in regulatory decision making. Here, we discuss in vitro TGx systems and their potential impact on risk assessment. We raise awareness of the rapid advancement of genomics technologies, which generates novel genomics features essential for enhanced risk assessment. We specifically emphasize the importance of reproducibility in utilizing TGx in the regulatory setting. We also highlight the role of machine learning (particularly deep learning) in developing TGx-based predictive models. Lastly, we touch on the topics of how TGx approaches could facilitate adverse outcome pathways (AOP) development and enhance read-across strategies to further regulatory application. Finally, we summarize current efforts to develop TGx for risk assessment and set out remaining challenges.
Topics: Animal Testing Alternatives; Animals; Humans; Machine Learning; Reproducibility of Results; Risk Assessment; Toxicogenetics
PubMed: 30594306
DOI: 10.1016/j.tips.2018.12.001 -
Current Drug Metabolism Mar 2008Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics and metabolomics) and toxicology. It is a scientific field that studies how the... (Review)
Review
Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics and metabolomics) and toxicology. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. It combines studies of mRNA expression, cell and tissue-wide protein expression and metabonomics to understand the role of gene-environment interactions in disease. One of the important aspects of toxicogenomics research is the development and application of bioinformatics tools and databases in order to facilitate the analysis, mining, visualizing and sharing of the vast amount of biological information being generated in this field. This rapidly growing area promises to have a large impact on many other scientific and medical disciplines as scientists could now generate complete descriptions of how components of biological systems work together in response to various stresses, drugs, or toxicants.
Topics: Animals; Chromatography, Gas; Chromatography, High Pressure Liquid; Electrophoresis, Capillary; Humans; Metabolism; Toxicogenetics
PubMed: 18336230
DOI: 10.2174/138920008783884696 -
International Journal of Molecular... Jul 2022Pollution is defined as the presence in or introduction of a substance into the environment that has harmful or poisonous effects [...].
Pollution is defined as the presence in or introduction of a substance into the environment that has harmful or poisonous effects [...].
Topics: Biomarkers; Risk Assessment; Toxicogenetics
PubMed: 35955413
DOI: 10.3390/ijms23158280 -
Advances in Biochemical... 2017This chapter reviews the current knowledge and recent progress in the field of environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods. In... (Review)
Review
This chapter reviews the current knowledge and recent progress in the field of environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods. In ecotoxicogenomics the omics technologies are applied for the detection and assessment of adverse effects in the environment, and thus are to be distinguished from omics used in human toxicology [Snape et al., Aquat Toxicol 67:143-154, 2004]. Transcriptomic methods in ecotoxicology are applied to gain a mechanistic understanding of toxic effects on organisms or populations, and thus aim to bridge the gap between cause and effect. A worthwhile effect-based interpretation of stressor induced changes on the transcriptome is based on the principle of phenotypic-anchoring [Paules, Environ Health Perspect 111:A338-A339, 2003]. Thereby, changes on the transcriptomic level can only be identified as effects if they are clearly linked to a specific stressor-induced effect on the macroscopic level. By integrating those macroscopic and transcriptomic effects, conclusions on the effect-inducing type of the stressor can be drawn. Stressor-specific effects on the transcriptomic level can be identified as stressor-specific induced pathways, transcriptomic patterns, or stressors-specific genetic biomarkers. In this chapter, examples of the combined application of macroscopic and transcriptional effects for the identification of environmental stressors, such as aquatic pollutants, are given and discussed. By means of these examples, challenges on the way to a standardized application of transcriptomics in ecotoxicology are discussed. This is also done against the background of the application of transcriptomic methods in environmental regulation such as the EU regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
Topics: Animals; Biological Assay; Ecology; Ecotoxicology; Environmental Monitoring; Environmental Pollutants; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Mutagenicity Tests; Mutagens; Risk Assessment; Toxicogenetics; Transcriptome
PubMed: 27864593
DOI: 10.1007/10_2016_15 -
Advances in Experimental Medicine and... 2018The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and... (Review)
Review
The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression. Toxicological responses of NPs have been discussed in this chapter with the aim to provide a clear understanding of the molecular mechanism of NPs induced toxicity both in in vivo and in vitro test models.
Topics: Animals; Gene Expression Regulation; Humans; Nanoparticles; Toxicogenetics
PubMed: 29453537
DOI: 10.1007/978-3-319-72041-8_9 -
Biomedicine & Pharmacotherapy =... Jul 2023More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards... (Review)
Review
More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards personalized treatment. Additionally, the promotion of non-animal testing has fueled the computational toxicogenomics as a pivotal part of the next-gen risk assessment paradigm. Artificial Intelligence (AI) has the potential to provid new ways analyzing the patient data and making predictions about treatment outcomes or toxicity. As personalized medicine and toxicogenomics involve huge data processing, AI can expedite this process by providing powerful data processing, analysis, and interpretation algorithms. AI can process and integrate a multitude of data including genome data, patient records, clinical data and identify patterns to derive predictive models anticipating clinical outcomes and assessing the risk of any personalized medicine approaches. In this article, we have studied the current trends and future perspectives in personalized medicine & toxicology, the role of toxicogenomics in connecting the two fields, and the impact of AI on personalized medicine & toxicology. In this work, we also study the key challenges and limitations in personalized medicine, toxicogenomics, and AI in order to fully realize their potential.
Topics: Humans; Artificial Intelligence; Precision Medicine; Toxicogenetics; Algorithms; Technology
PubMed: 37121152
DOI: 10.1016/j.biopha.2023.114784 -
Environmental Science & Technology Aug 2022The toxicity evaluation system of environmental pollutants has undergone numerous changes due to the application of new technologies. Single-cell toxicogenomics is... (Review)
Review
The toxicity evaluation system of environmental pollutants has undergone numerous changes due to the application of new technologies. Single-cell toxicogenomics is rapidly changing our view on environmental toxicology by increasing the resolution of our analysis to the level of a single cell. Applications of this technology in environmental toxicology have begun to emerge and are rapidly expanding the portfolio of existing technologies and applications. Here, we first summarized different methods involved in single-cell isolation and amplification in single-cell sequencing process, compared the advantages and disadvantages of different methods, and analyzed their development trends. Then, we reviewed the main advances of single-cell toxicogenomics in environmental toxicology, emphatically analyzed the application prospects of this technology in identifying the target cells of pollutants in early embryos, clarifying the heterogeneous response of cell subtypes to pollutants, and finding pathogenic bacteria in unknown microbes, and highlighted the unique characteristics of this approach with high resolution, high throughput, and high specificity by examples. We also offered a prediction of the further application of this technology and the revolution it brings in environmental toxicology. Overall, these advances will provide practical solutions for controlling or mitigating exogenous toxicological effects that threaten human and ecosystem health, contribute to improving our understanding of the physiological processes affected by pollutants, and lead to the emergence of new methods of pollution control.
Topics: Ecosystem; Ecotoxicology; Environmental Pollutants; Humans; Toxicogenetics; Toxicology
PubMed: 35881918
DOI: 10.1021/acs.est.2c01098 -
Frontiers in Bioscience (Landmark... Oct 2022Environmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances... (Review)
Review
Environmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health.
Topics: Animals; Humans; Toxicogenetics; Genomics; Proteomics; Computational Biology; Metabolomics
PubMed: 36336867
DOI: 10.31083/j.fbl2710294 -
Nihon Yakurigaku Zasshi. Folia... Nov 2012
Review
Topics: Animals; Biomarkers, Pharmacological; Glutathione; Liver; Rats; Toxicogenetics
PubMed: 23138320
DOI: 10.1254/fpj.140.221 -
Environmental Research Jun 2019It is still a major challenge to protect humans at workplaces and in the environment. To cope with this task, it is a prerequisite to obtain detailed information on the... (Review)
Review
It is still a major challenge to protect humans at workplaces and in the environment. To cope with this task, it is a prerequisite to obtain detailed information on the extent of chemical perturbations of biological pathways, in particular, adaptive vs. adverse effects and the dose-response relationships. This knowledge serves as the basis for the classification of non-carcinogens and carcinogens and for further distinguishing carcinogens in genotoxic (DNA damaging) or non-genotoxic compounds. Basing on quantitative dose-response relationships, points of departures can be derived for chemical risk assessment. In recent years, new methods have shown their capability to support the established rodent models of carcinogenicity testing. In vitro high throughput screening assays assess more comprehensively cell response. In addition, omics technologies were applied to study the mode of action of chemicals whereby the term "toxicogenomics" comprises various technologies such as transcriptomics, epigenomics, or metabolomics. This review aims to summarize the current state of toxicogenomic approaches in risk science and to compare them with established ones. For example, measurement of global transcriptional changes generates meaningful information for toxicological risk assessment such as accurate classification of genotoxic/non-genotoxic carcinogens. Alteration in mRNA expression offers previously unknown insights in the mode of action and enables the definition of key events. Based on these, benchmark doses can be calculated for the transition from an adaptive to an adverse state. In short, this review assesses the potential and challenges of transcriptomics and addresses the impact of other omics technologies on risk assessment in terms of hazard identification and dose-response assessment.
Topics: Carcinogenicity Tests; Carcinogens; Dose-Response Relationship, Drug; Humans; Risk Assessment; Toxicogenetics
PubMed: 30909101
DOI: 10.1016/j.envres.2019.03.025