Application of the Emerging Technologies in Toxicogenomics: An Overview

유소연,Saswati Paul,황승용 한국바이오칩학회 2016 BioChip Journal Vol.10 No.4

Toxicogenomics is a rapidly developing area of research which combines the understanding of molecular and cellular regulation in response to interaction of chemical stressors. Moreover, the emergence of comprehensive research method covering genomic, proteomic, and metabonomics analysis including bioinformatics has further substantiated the field of toxicogenomics. Thus, evaluation of such integrated analysis, conversing from variety of experimental techniques, along with the resulting database can decipher the importantance of such techniques in toxicogenomics. In addition, recent integration of epigenetic study (DNA Methylation, histone modification, small and noncoding RNAs) with toxicogenomics can pave the path to elucidate, highly reliable research results. The objective of the present review is to expand these understandings of toxicogenomics approach and validate the contribution of the developing research methods (genome, proteome, metabolites) to emphasize its importance in future toxicogenomics research.

Single-cell transcriptomics to understand the cellular heterogeneity in toxicology

Seon hwa Kim,조수영 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.2

Background Identification of molecular signatures from omics studies is widely applied in toxicological studies, and the evaluation of potential toxic effects provides novel insights into molecular resolution. Objective The prediction of toxic effects and drug tolerance provides important clues regarding the mode of action of target compounds. However, heterogeneity within samples makes toxicology studies challenging because the purity of the target cell in the samples remains unknown until their actual utilization. Result Single-cell resolution studies have been suggested in toxicogenomics, and several studies have explained toxic effects and drug tolerance using heterogeneous cells in both in vivo and in vitro conditions. In this review, we presented an understanding of single-cell transcriptomes and their applications in toxicogenomics. Conclusion The most toxicological mechanism in organisms occurs through intramolecular combinations, and heterogeneity issues have reached a surmountable level. We hope this review provides insights to successfully conduct future studies on toxicology. Purpose of the review Toxicogenomics is an interdisciplinary field between toxicology and genomics that was successfully applied to construct molecular profiles in a broad spectrum of toxicology. However, heterogeneity within samples makes toxicology studies challenging because the purity of target cell in the samples remains unknown until their actual utilisation. In this review, we presented an understanding of single-cell transcriptomes and their applications in toxicogenomics. Recent findings A high-throughput techniques have been used to understand cellular heterogeneity and molecular mechanisms at toxicogenomics. Single-cell resolution analysis is required to identify biomarkers of explain toxic effect and in order to understand drug tolerance.

Integrative toxicogenomics-based approach to risk assessment of heavy metal mixtures/complexes: strategies and challenges

Preeyaporn Koedrith,Hye Lim Kim,Young Rok Seo 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.3

Human exposure to metallic elements ranging from single metal ionic salt, metal compounds, and metal mixtures that may occur naturally, as well as from human activities and industrial applications. Some metals including arsenic, cadmium, chromium, lead, mercury, and nickel in both single element and mixture forms render confounding health effects and ultimately cause cancer. Studies of heavy metal-mediated global aberration using non-targeted multiple toxicogenomic technologies might help to elucidate environmentally relevant disorders, as well as to monitor biomarker of exposure and predict the health risk toward environmental toxicants. We describe recent toxicogenomic studies on heavy metal mixtures as well as relevant mechanism of toxicity and molecular signatures. On the basis of system toxicology approach, integrative toxicogenomic and bioinformatic tools might represent the biological pathways linked to disorders. We also strongly suggest that the toxicogenomic data can be adopted to risk assessment process. Furthermore, we mention challenges in utility of toxicogenomic studies data to risk assessment process of toxicity of metal mixtures. Overall, we realize that application and interpretation of toxicogenomic data regarding to their strengths and weaknesses would potentiate chemical risk assessment.

Use of genomic techniques to screen for potential immunotoxic effects

( Kyung Hee Sohn ),( In Young Kim ),( Juno H. Eom ),( Jong Kwon Lee ),( Jin Ho Kim ),( Jung Hun Ju ),( Hwa Chul Jung ),( Ji Hye Lee ),( Moon Sung Choi ),( Hyung Soo Kim ),( Seung Hee Kim ),( Kui Lea P 한국동물실험대체법학회 2007 한국동물실험대체법학회 학술대회집 Vol.2007 No.1

Application of genomic data to elucidate or predict an organism`s response to a toxicant is referred to as toxicogenomics. Toxicogenomics is increasingly applied to study alterations in gene expression after immunotoxicant exposure, but published data are still limited. The present study was performed to explore the potential role of genomics techniques for immunotoxicity screening. Genomic data alone are, however, insufficient to screen chemicals for immunotoxic potentialand should be anchored to a phenotypic marker. Therefore, we performed both DNA microarray analysis and traditional immunotoxicity tests to clarify the connection between changes in gene expression and pathological/functional endpoints. Cyclosporin A(CsA), tacrolimus(FK506), hexachlorobenzene(HCB) were used as immunotoxicants. Immunological effects of these chemicals on Balb/c mouse were confirmed by changes in parameters related to pathology, hematology, innate immunity, humoral immunity and cellular immunity. On the other hand, total RNAs were prepared from spleens and thymuses of Balb/c mice which were orally dosed with each chemical for 28 days. The changes in gene expression levels were analyzed using Applied Biosystems Mouse Genome Survey Microarray. Differentially expressed genes(DEG) were selected and classified through related biological processes and signal pathways. Comparative toxicogenomic analysis from these differential gene expression profiles was performed. Ultimately, the use of genomics techniques as a potential screening tools for immunotoxicity and as a technique to identify mode or mechanism of action will be discussed.

바이오 디지털 콘텐츠를 이용한 독성의 분석

강진석(Jin Seok Kang) 한국디지털콘텐츠학회 2010 한국디지털콘텐츠학회논문지 Vol.11 No.1

Numerous bio-digital contents have been produced by new technology using biochip and others for analyzing early chemical-induced genes. These contents have little meaning by themselves, and so they should be modified and extracted after consideration of biological meaning. These include genomics, transcriptomics, protenomics, metabolomics, which combined into omics. Omics tools could be applied into toxicology, forming a new field of toxicogenomics. It is possible that approach of toxicogenomics can estimate toxicity more quickly and accurately by analyzing gene/protein/metabolite profiles. These approaches should help not only to discover highly sensitive and predictive biomarkers but also to understand molecular mechanism(s) of toxicity, based on the development of analysing technology. Furthermore, it is important that bio-digital contents should be obtained from specific cells having biological events more than from whole cells. Taken together, many bio-digital contents should be analyzed by careful calculating algorism under well-designed experimental protocols, network analysis using computational algorism and related profound databases.

XPERNATO-TOX: an Integrated Toxicogenomics Knowledgebase

Woo Jung-Hoon,Kim Hyeoun-Eui,Kong Gu,Kim Ju-Han Korea Genome Organization 2006 Genomics & informatics Vol.4 No.1

Toxicogenomics combines transcriptome, proteome and metabolome profiling with conventional toxicology to investigate the interaction between biological molecules and toxicant or environmental stress in disease caution. Toxicogenomics faces the problems of comparison and integration across different sources of data. Cause of unusual characteristics of toxicogenomic data, researcher should be assisted by data analysis and annotation for getting meaningful information. There are already existing repositories which claim to stand for toxicogenomics database. However, those just contain limited abilities for toxicogenomic research. For supporting toxicologist who comes up against toxicogenomic data flood, now we propose novel toxicogenomics knowledgebase system, XPERANTO-TOX. XPERANTO-TOX is an integrated system for toxicogenomic data management and analysis. It is composed of three distinct but closely connected parts. Firstly, Data Storage System is for reposit many kinds of '-omics' data and conventional toxicology data. Secondly, Data Analysis System consists of analytical modules for integrated toxicogenomics data. At last, Data Annotation System is for giving extensive insight of data to researcher.

Application of Toxicogenomic Technology for the Improvement of Risk Assessment

Hwang, Myung-Sil,Yoon, Eun-Kyung,Kim, Ja-Young,Son, Bo-Kyung,Jang, Dong-Deuk,Yoo, Tae-Moo The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.3

Recently, there has been scientific discussion on the utility of -omics techniques such as genomics, proteomics, and metabolomics within toxicological research and mechanism-based risk assessment. Toxicogenomics is a novel approach integrating the expression analysis of genes (genomic) or proteins (proteomic) with traditional toxicological methods. Since 1999, the toxicogenomic approach has been extensively applied for regulatory purposes in order to understand the potential toxic mechanisms that result from chemical compound exposures. Therefore, this article's purpose was to consider the utility of toxicogenomic profiles for improved risk assessment, explore the current limitations in applying toxicogenomics to regulation, and finally, to rationalize possible avenues to resolve some of the major challenges. Based on many recent works, the significant impact toxicogenomic techniques would have on human health risk assessment is better identification of toxicity pathways or mode-of-actions (MOAs). In addition, the application of toxicogenomics in risk assessment and regulation has proven to be cost effective in terms of screening unknown toxicants prior to more extensive and costly experimental evaluation. However, to maximize the utility of these techniques in regulation, researchers and regulators must resolve many parallel challenges with regard to data collection, integration, and interpretation. Furthermore, standard guidance has to be prepared for researchers and assessors on the scientifically appropriate use of toxicogenomic profiles in risk assessment. The National Institute of Toxicological Research (NITR) looks forward to an ongoing role as leader in addressing the challenges associated with the scientifically sound use of toxicogenomics data in risk assessment.

Eco-toxicogenomics Research with Fish

Park, Kyeong-Seo,Kim, Han-Na,Gu, Man-Bock The Korean Society of Toxicogenomics and Toxicopro 2005 Molecular & cellular toxicology Vol.1 No.1

There are some critical drawbacks in the use of biomarkers for a global assessment of the toxicological impacts many chemicals and environmental pollutants have, primarily due to an individual biomarker's specificity for an explicit chemical or toxicant. In other words, the biomarker-based assessment methodology used to analyze toxicological effects lacks a high-throughput capability. Therefore, eco-toxicogenomics, or the study of toxicogenomics with organisms present within a given environmental locale, has recently been introduced with the advent of the so-called "-omics" era, which began with the creation of microarray technologies. Fish are comparable with humans in their toxicological responses and thus data from toxicogenomic studies performed with fish could be applied, with appropriate tools and implementation protocols, to the evaluation of environments where human or animal health is of concern. At present, there have been very active research streams for developing expression sequence tag (EST) databases (DBs) for zebra fish and rainbow trout. Even though few reports involve toxicogenomic studies with fish, a few groups have successfully fabricated and used cDNA microarrays or oligo DNA chips when studying the toxicological impacts of hypoxia or some toxicants with fish. Furthermore, it is strongly believed that this technology can also be implemented with non-model fish. With the standardization of DNA microarray technologies and ample progress in bioinformatics and proteomic technologies, data obtained from DNA microarray technologies offer not only multiple biomarker assays or an analysis of gene expression profiles, but also a means of elucidating gene networking, gene-gene relations, chemical-gene interactions, and chemical-chemical relationships. Accordingly, the ultimate target of eco-toxicogenomics should be to predict and map the pathways of stress propagation within an organism and to analyze stress networking.

Classification of Environmental Toxicants Using HazChem Human Array V2

An, Yu-Ri,Kim, Seung-Jun,Park, Hye-Won,Kim, Jun-Sub,Oh, Moon-Ju,Kim, Youn-Jung,Ryu, Jae-Chun,Hwang, Seung-Yong The Korean Society of Toxicogenomics and Toxicopro 2009 Molecular & cellular toxicology Vol.5 No.3

Toxicogenomics using microarray technology offers the ability to conduct large-scale detections and quantifications of mRNA transcripts, particularly those associated with alterations in mRNA stability or gene regulation. In this study, we developed the HazChem Human Array V2 using the Agilent Sure-Print technology-based custom array, which is expected to facilitate the identification of environmental toxicants. The array was manufactured using 600 VOCs and PAHs-specific genes identified in previous studies. In order to evaluate the viability of the manufactured HazChem human array V2, we analyzed the gene expression profiles of 9 environmental toxicants (6 VOCs chemicals and 3 PAHs chemicals). As a result, nine toxicants were separated into two chemical types-VOCs and PAHs. After the chip validations with VOCs and PAHs, we conducted an expression profiling comparison of additional chemical groups (POPs and EDCs) using data analysis methods such as hierarchical clustering, 1-way ANOVA, SAM, and PCA. We selected 58 genes that could be classified into four chemical types via statistical methods. Additionally, we selected 63 genes that evidenced significant alterations in expression with all 13 environmental toxicants. These results suggest that the HazChem Human Array V2 will expedite the development of a screening system for environmentally hazardous materials at the level of toxicogenomics in the future.

Promising Next Generation Technology in Toxicology-Toxicogenomics

Ryu, Jae-Chun,Kim, Meyoung-Kon,Cho, Man-Ho,Chun, Tae-Hoon The Korean Society of Toxicogenomics and Toxicopro 2005 Molecular & cellular toxicology Vol.1 No.1

Toxicology is a multidisciplinary field, and an important science that impacts both environmental health regulation and the development and practice of medicine. The rapid progress in cellular and molecular biology, like many other branches of biomedical research, toxicology is now experiencing a renaissance fueled by the application of "omic" technologies to gain a better understanding of the biological basis of toxicology of drugs and other environmental factors. In this review on current progress on toxicology, the future perspective, concept, approaches and applications of toxicogenomics as next generation promising technology in toxicology field will be described.