-
Critical Reviews in Toxicology Jan 2015Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those... (Comparative Study)
Comparative Study Review
Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water.
Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.
Topics: Animals; Benzo(a)pyrene; Carcinogens; Drinking Water; Gene Expression Regulation; Genomics; Humans; Mice; Risk Assessment; Species Specificity; Toxicogenetics
PubMed: 25605026
DOI: 10.3109/10408444.2014.973934 -
Frontiers in Genetics 2019
PubMed: 30891065
DOI: 10.3389/fgene.2019.00165 -
Computational and Structural... 2022The recent advancements in toxicogenomics have led to the availability of large omics data sets, representing the starting point for studying the exposure mechanism of...
The recent advancements in toxicogenomics have led to the availability of large omics data sets, representing the starting point for studying the exposure mechanism of action and identifying candidate biomarkers for toxicity prediction. The current lack of standard methods in data generation and analysis hampers the full exploitation of toxicogenomics-based evidence in regulatory risk assessment. Moreover, the pipelines for the preprocessing and downstream analyses of toxicogenomic data sets can be quite challenging to implement. During the years, we have developed a number of software packages to address specific questions related to multiple steps of toxicogenomics data analysis and modelling. In this review we present the Nextcast software collection and discuss how its individual tools can be combined into efficient pipelines to answer specific biological questions. Nextcast components are of great support to the scientific community for analysing and interpreting large data sets for the toxicity evaluation of compounds in an unbiased, straightforward, and reliable manner. The Nextcast software suite is available at: ( https://github.com/fhaive/nextcast).
PubMed: 35386103
DOI: 10.1016/j.csbj.2022.03.014 -
Protein & Cell May 2018Inter-individual heterogeneity in drug response is a serious problem that affects the patient's wellbeing and poses enormous clinical and financial burdens on a societal... (Review)
Review
Inter-individual heterogeneity in drug response is a serious problem that affects the patient's wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recognized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposition (absorption, distribution, metabolism and excretion). In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.
Topics: Anti-Infective Agents; Biodiversity; Humans; Microbiota; Pharmacogenetics; Precision Medicine; Toxicogenetics
PubMed: 29705929
DOI: 10.1007/s13238-018-0547-2 -
Frontiers in Genetics 2022The Frontiers Media family has over 200 journals, which are each headed by usually one Field Chief Editor, and several thousand specialty sections, which are each headed... (Review)
Review
The Frontiers Media family has over 200 journals, which are each headed by usually one Field Chief Editor, and several thousand specialty sections, which are each headed by one or more Specialty Chief Editors. The year 2021 was the 10th anniversary of the founding of the Frontiers in Genetics journal and the Frontiers in Toxicogenomics specialty section of this journal. In 2021, we also announce one of the newest of the Frontiers journals-Frontiers in Toxicology which is part of the Frontiers Media family of journals but independent of Frontiers in Genetics. Dr. Ruden is the founding, and currently sole, Specialty Chief Editor of Frontiers in Toxicogenomics and one of 9 Specialty Chief Editors of Frontiers in Toxicology. As of 2021, Frontiers in Toxicogenomics has published over 138 articles and has over 370 Editors including 90 Associate Editors and 280 Review Editors. The Frontiers in Genetics impact factor was initially approximately 2.5 when it was first listed in PubMed in 2015 and has risen steadily to its current value of 4.8, which is typical for the majority of the over 200 Frontiers journals that have established impact factors. In this overview of the first decade of Frontiers in Toxicogenomics, we discuss the top 5 articles with the highest Scopus citations, which were all written in the first few years of the journal. The article with the highest number of citations, with 353 Scopus over 600 Google Scholar citations, and the highest average number of citations (67) that steadily increased from 10 citations in 2013 to 119 citations in 2021, was written in 2012 by Dr. Ruden's laboratory and titled, "Using as a model for genotoxic chemical mutational studies with a new program, SnpSift." The five most influential authors who published in the journal in the past 10 years based on Scopus citations of a particular paper are Dr. Ruden's laboratory, with 353 Scopus citations for the SnpSift paper mentioned above; Drs. Brock Christensen and Carmen J. Marsit, with 86 Scopus citations for their review, "Epigenomics in environmental health"; Dr. Michael Aschner and colleagues, with 61 Scopus citations for their paper "Genetic factors and manganese-induced neurotoxicity"; and Dr. Sandra C. dos Santos and colleagues, with 59 Scopus citations for their paper, "Yeast toxicogenomics: genome-wide responses to chemical stresses with impact in environmental health, pharmacology, and biotechnology." While the top 5 papers were published in the early years of the journal, we will also discuss a more recent article published in 2018 on a comparison of RNA-seq and microarray methods by Dr. Michael Liguori's laboratory, "Comparison of RNA-Seq and Microarray Gene Expression Platforms for the Toxicogenomic Evaluation of Liver From Short-Term Rat Toxicity Studies," that far exceeds the number of downloads and views of all the other articles published in the first 10 years of the journal and will likely be a top cited paper in the second decade highlights of this journal. Finally, we discuss where the Frontiers in Toxicogenomics specialty journal and the Frontiers in Toxicology journal will go to advance the field of toxicogenomics, and more generally, toxicology, in the future.
PubMed: 36171875
DOI: 10.3389/fgene.2022.979761 -
BMC Bioinformatics Oct 2009The Comparative Toxicogenomics Database (CTD) is a publicly available resource that promotes understanding about the etiology of environmental diseases. It provides... (Comparative Study)
Comparative Study
BACKGROUND
The Comparative Toxicogenomics Database (CTD) is a publicly available resource that promotes understanding about the etiology of environmental diseases. It provides manually curated chemical-gene/protein interactions and chemical- and gene-disease relationships from the peer-reviewed, published literature. The goals of the research reported here were to establish a baseline analysis of current CTD curation, develop a text-mining prototype from readily available open source components, and evaluate its potential value in augmenting curation efficiency and increasing data coverage.
RESULTS
Prototype text-mining applications were developed and evaluated using a CTD data set consisting of manually curated molecular interactions and relationships from 1,600 documents. Preliminary results indicated that the prototype found 80% of the gene, chemical, and disease terms appearing in curated interactions. These terms were used to re-rank documents for curation, resulting in increases in mean average precision (63% for the baseline vs. 73% for a rule-based re-ranking), and in the correlation coefficient of rank vs. number of curatable interactions per document (baseline 0.14 vs. 0.38 for the rule-based re-ranking).
CONCLUSION
This text-mining project is unique in its integration of existing tools into a single workflow with direct application to CTD. We performed a baseline assessment of the inter-curator consistency and coverage in CTD, which allowed us to measure the potential of these integrated tools to improve prioritization of journal articles for manual curation. Our study presents a feasible and cost-effective approach for developing a text mining solution to enhance manual curation throughput and efficiency.
Topics: Computational Biology; Databases, Factual; Gene Regulatory Networks; Information Storage and Retrieval; Toxicogenetics
PubMed: 19814812
DOI: 10.1186/1471-2105-10-326 -
Toxicologic Pathology Oct 2023Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related...
Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related to the dynamic range of the assays, sensitivity, cost, and technological limitations, transcriptomic approaches are predominantly used in toxicogenomics. Toxicogenomics is being used to understand the mechanisms of toxicity and carcinogenicity, evaluate the translational relevance of toxicological responses from in vivo and in vitro models, and identify predictive biomarkers of disease and exposure. In this session, a brief overview of various transcriptomic technologies and practical considerations related to experimental design was provided. The advantages of gene network analyses to define mechanisms were also discussed. An assessment of the utility of toxicogenomic technologies in the environmental and pharmaceutical space showed that these technologies are being increasingly used to gain mechanistic insights and determining the translational relevance of adverse findings. Within the environmental toxicology area, there is a broader regulatory consideration of benchmark doses derived from toxicogenomics data. In contrast, these approaches are mainly used for internal decision-making in pharmaceutical development. Finally, the development and application of toxicogenomic signatures for prediction of apical endpoints of regulatory concern continues to be area of intense research.
Topics: Toxicogenetics; Liver; Proteomics; Gene Expression Profiling; Transcriptome
PubMed: 38288963
DOI: 10.1177/01926233241227942 -
Journal of Food and Drug Analysis Nov 2022The co-occurrence and accumulation of mycotoxin in food and feed constitutes a major issue to food safety, food security, and public health. Accurate and sensitive... (Review)
Review
The co-occurrence and accumulation of mycotoxin in food and feed constitutes a major issue to food safety, food security, and public health. Accurate and sensitive mycotoxins analysis can avoid toxin contamination as well as reduce food wastage caused by false positive results. This mini review focuses on the recent advance in detection methods for multiple mycotoxins, which mainly depends on immunoassay technologies. Advance immunoassay technologies integrated in mycotoxin analysis enable simultaneous detection of multiple mycotoxins and enhance the outcomes' quality. It highlights toxicogenomic as novel approach for hazard assessment by utilizing computational methods to map molecular events and biological processes. Indeed, toxicogenomic is a powerful tool to understand health effects from mycotoxin exposure as it offers insight on the mechanisms by which mycotoxins exposures cause diseases.
Topics: Mycotoxins; Toxicogenetics; Food Contamination; Immunoassay; Animal Feed
PubMed: 36753365
DOI: 10.38212/2224-6614.3430 -
Ecotoxicology and Environmental Safety Jun 2021The combined toxicological assessment provides a realistic approach for hazard evaluation of chemical cocktails that co-existed in the environment. This review provides... (Review)
Review
The combined toxicological assessment provides a realistic approach for hazard evaluation of chemical cocktails that co-existed in the environment. This review provides a holistic insight into the studies highlighting the mixture toxicity of the endocrine-disrupting chemicals (EDCs), especially focusing on the screening of biochemical pathways and other toxicogenetic endpoints. Reviewed literature showed that numerous multiplexed toxicogenomic techniques were applied to determine reproductive effects in vertebrates, but limited studies were found in non-mammalian species after mixture chemical exposure. Further, we found that the experimental design and concentration selection are the two important parameters in mixture toxicity studies that should be time- and cost-effective, highly precise, and environmentally relevant. A summary of EDC mixtures affecting the thyroid axis, estrogen axis, androgen axis, growth stress, and immune system via in vivo bioassays was also presented. It is interesting to mention that majority of estrogenic effects of the mixtures were sex-dependent, particularly observed in male fish as compared to female fish. Further, the androgen axis was perturbed with serious malformations in male rat testis (epididymal or gubernacular lesions, and deciduous spermatids). Also, transgenerational epigenetic effects were promoted in the F and F generations in the form of DNA methylation epimutations in sperm, increasing polycystic ovaries and reducing the offspring. Similarly, increased oxidative stress, high antioxidant enzymatic activities, disturbed estrous cycle, and decreased steroidogenesis were the commonly found effects after acute or chronic exposure to EDC mixtures. Importantly, the concentration addition (CA) and independent action (IA) models became more prevalent and suitable predictive models to unveil the prominence of synergistic estrogenic and anti-androgenic effects of chemical mixtures. More importantly, this review encompasses the research challenges and gaps in the existing knowledge and specific future research perspectives on combined toxicity.
Topics: Androgen Antagonists; Animals; Biological Assay; DNA Methylation; Endocrine Disruptors; Estrogens; Female; Fishes; Male; Rats; Reproduction; Spermatozoa; Thyroid Gland
PubMed: 33735605
DOI: 10.1016/j.ecoenv.2021.112136 -
Archives of Toxicology Jun 2020The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of... (Review)
Review
The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as "omics" approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.
Topics: Animals; Carcinogenicity Tests; Carcinogens; DNA Damage; Humans; Mutagenicity Tests; Mutagens; Risk Assessment; Toxicogenetics
PubMed: 32542409
DOI: 10.1007/s00204-020-02733-2