Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Shen, Hua; McHale, Cliona M.; Smith, Martyn T.; Zhang, Luoping

doi:10.1016/j.mrrev.2015.01.002

Cited by 32 publications

(16 citation statements)

References 139 publications

(168 reference statements)

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“…Contrasting with toxicogenomics approaches based on the expressome (e.g., transcriptomics, proteomics and metabolomics) that indirectly correlate chemical exposure with gene products (e.g., mRNA, protein, metabolites), functional genomics can directly link genes and their functions to tolerance to substance exposure, providing unprecedented mechanistic insight into the critical genes and/or pathways modulated by chemicals. − Functional genomics involves genome-scale knockout or knockdown, followed by the screening of genes whose loss-of-function confers resistance or sensitivity to toxicity at the phenotype level (e.g., cell death) following toxic substance exposure. In unicellular organisms, functional genomic screening has been conducted on various species, such as bacteria, yeast …”

Section: Using Functional Genomics To Study Novel Molecular Mechanism...mentioning

confidence: 99%

Omics Advances in Ecotoxicology

Zhang

Xia

Wang

et al. 2018

Environ. Sci. Technol.

142

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Toxic substances in the environment generate adverse effects at all levels of biological organization from the molecular level to community and ecosystem. Given this complexity, it is not surprising that ecotoxicologists have struggled to address the full consequences of toxic substance release at ecosystem level, due to the limits of observational and experimental tools to reveal the changes in deep structure at different levels of organization. -Omics technologies, consisting of genomics and ecogenomics, have the power to reveal, in unprecedented detail, the cellular processes of an individual or biodiversity of a community in response to environmental change with high sample/observation throughput. This represents a historic opportunity to transform the way we study toxic substances in ecosystems, through direct linkage of ecological effects with the systems biology of organisms. Three recent examples of -omics advance in the assessment of toxic substances are explored here: (1) the use of functional genomics in the discovery of novel molecular mechanisms of toxicity of chemicals in the environment; (2) the development of laboratory pipelines of dose-dependent, reduced transcriptomics to support high-throughput chemical testing at the biological pathway level; and (3) the use of eDNA metabarcoding approaches for assessing chemical effects on biological communities in mesocosm experiments and through direct observation in field monitoring. -Omics advances in ecotoxicological studies not only generate new knowledge regarding mechanisms of toxicity and environmental effect, improving the relevance and immediacy of laboratory toxicological assessment, but can provide a wholly new paradigm for ecotoxicology by linking ecological models to mechanism-based, systems biology approaches.

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Section: Using Functional Genomics To Study Novel Molecular Mechanism...mentioning

confidence: 99%

Omics Advances in Ecotoxicology

Zhang

Xia

Wang

et al. 2018

Environ. Sci. Technol.

142

View full text Add to dashboard Cite

show abstract

“…Chemical toxicants act by many different mechanisms, however, the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and the identification of genes associated with a toxicity phenotype following toxicant exposure [127][128][129].…”

Section: Crispr/cas9 Genome-editingmentioning

confidence: 99%

Biomarkers and in vitro strategies for nephrotoxicity and renal disease assessment

Soares¹,

Souza²,

Cronin³

et al. 2020

Nephrol Renal Dis

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Acute kidney injury (AKI) is a global public health concern, impacting nearly 13.3 million patients and resulting in three million deaths per year. Chronic kidney disease (CKD) has increased by 135% since 1990, representing the pathology with the fastest growth rate worldwide. The annual costs of dialysis and kidney transplants range between US$35,000 and US$100,000 per patient. Despite its great impact, kidney disease has remained mostly asymptomatic for many years. AKI continues to be a major, unmet medical condition for which there are no pharmacological treatments available, while animal models are limited to provide direction for therapeutic translation into humans. Currently, serum creatinine is the standard biomarker to identify nephrotoxicity; however, it is a late stage biomarker. Hence, there is a pressing need to study in vitro biomarkers for the assessment of nephrotoxicity in order to develop new and safer drugs. Understanding of the mechanisms by which molecules produce nephrotoxicity is vital in order to both prevent adversity and treat kidney injury. In this review, we address new technologies and models that may be used to identify earlier biomarkers and pathways involved in nephrotoxicity, such as cell culture, omic approaches, bioinformatics platform, CRISPR/ Cas9 genome-editing, in silico, organoids and 3D bioprinting, considering adverse outcome pathways (AOP).

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“…A pathogenic variation can prompt sickness or cause various disarrange. Nonetheless, comprehension of pathogenic instruments makes an chance to anticipate serious results by creating novel analytic devices and by planning very successful medications for the infection (5,6). To accomplish this point it is important to perform extensive scale useful genome examination that includes diverse fields of study: genomics, epigenomics, transcriptomics, proteomics, and interactomics.…”

Section: Introductionmentioning

confidence: 99%

A Survey of Methods for Genome Functional Analysis in Comparative Genomics

Udayaraju¹,

Varma²,

Sujitha³

2018

IJET

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In biomedical technologies, Gene functional analysis is an emerging concept in understands the DNA sequence and gene product analysis and gene interaction in different real time medical applications. Finding data sequences of gene functionalities. There are many techniques have been used to progress functionality of functionality of genome analysis. In this paper, we present algorithmic, calculation oriented and mathematical comparison under analysis of genome. We develop techniques for dynamic and automatic calculation of Genome relations; these relations are enabled in automatic identification of orthodox for Genome from redundant Genes in yeast Genome. We present a method to identify automatic protein to protein interaction Based on related patterns related to specific presentations, we observe understand frame of functional proteins were developed to find Gene identification with accurate and reliable formations like sensitivity & specificity. We also present methods for systematic "denovo" identification of motifs. The techniques do not depend on previous information of gene operate and in that way stand out from the present literary works on computational design finding. Based on the genome-wide preservation styles of known elements, we designed three preservation requirements that we used to discover novel motifs. Our comparative results give comparative genomic to process our outstanding of any pieces. Our proposed techniques are flexible to verify comprehensive data genes and provide reliable research on complicated genomes on human specifications.

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Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Cited by 32 publications

References 139 publications

Omics Advances in Ecotoxicology

Omics Advances in Ecotoxicology

Biomarkers and in vitro strategies for nephrotoxicity and renal disease assessment

A Survey of Methods for Genome Functional Analysis in Comparative Genomics

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