Blood transcriptomics: applications in toxicology

Abstract

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article.

A Meta-Analysis of the Performance of a Blood-Based Exposure Response Gene Signature Across Clinical Studies on the Tobacco Heating System 2.2 (THS 2.2)

“…Therefore, the value of blood-based gene expression profiling resides in the genes, in which expression pattern is distinctively representative of an exposure or a disease. For example, blood-based gene signatures have been shown to reflect different lung pathologies in patients (Showe et al, 2009; Rotunno et al, 2011; Zander et al, 2011; Bloom et al, 2013; DePianto et al, 2014; Huang et al, 2015) and even toxicant exposures (LaBreche et al, 2011; Beineke et al, 2012; Joseph et al, 2013; Bushel et al, 2016).…”

The sbv IMPROVER Systems Toxicology computational challenge: Identification of human and species-independent blood response markers as predictors of smoking exposure and cessation status

“…Exogenous chemicals (e.g., lead), chemical-derived metabolites, and endogenous molecules produced by primarily exposed organs (e.g., lung, gut) can pass into the blood stream and may induce molecular changes in blood cells [1]. Therefore, investigating whether specific markers in response to chemical exposure can be identified in blood cells may be highly valuable for monitoring chemical exposure [2, 3]. Interestingly, new ‘omics’ technologies (e.g., genomics, transcriptomics, proteomics, metabolomics, lipidomics) can be applied to toxicity testing in order to increase efficiency and provide a more data- and system-driven approach to exposure response assessment [3, 4].…”

“…In liver and pulmonary toxicity studies, gene signatures have been identified successfully in blood showing (i) capability to predict exposure and toxicity to chemicals such as acetaminophen in liver (drug-induced liver injury) or crystalline silica in lung; (ii) superior sensitivity as predictors of toxicity compared with the classical toxicity markers in rats; and (iii) to some extent, similarities in pathways and functions that are perturbed in primary tissue and blood [3]. These findings, in addition to its easy access, make blood highly relevant as a surrogate to identify gene expression-based signatures as specific markers for toxicological evaluation and risk assessment.…”

Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study

“…Increasing sequencing depth and ever-expanding coverage of next generation sequencing technology has made RNA-Seq an attractive approach for the identification of DEG in response to several different stimuli [ 73 , 74 ]. Molecular profiling of circulating blood cells has been associated with physiological, toxicological and pathological events originating from different tissues and organs in the body making it a rich source for potential biomarker identification [ 33 , 75 , 76 , 77 , 78 , 79 ] for the evaluation of treatment responses [ 45 , 80 , 81 ]. Our study consisted of whole blood RNA samples averaging 70M reads.…”