Transcriptomics in toxicogenomics, Part I: Experimental design, technologies, publicly available data, and regulatory aspects

Pia Anneli Sofia Kinaret , Angela Serra , Antonio Federico , Pekka Kohonen , Penny Nymark , Irene Liampa , My Kieu Ha , Jang-Sik Choi , Karolina Jagiełło , Natasha Sanabria , Georgia Melagraki , Luca Cattelani , Michele Fratello , Haralambos Sarimveis , Antreas Afantitis , Tae-Hyun Yoon , Mary Gulumian , Roland Grafström , Tomasz Puzyn , Dario Greco

Abstract

The starting point of successful hazard assessment is the generation of unbiased and trustworthy data. Conventional toxicity testing deals with extensive observations of phenotypic endpoints in vivo and complementing in vitro models. The increasing development of novel materials and chemical compounds dictates the need for a better understanding of the molecular changes occurring in exposed biological systems. Transcriptomics enables the exploration of organisms’ responses to environmental, chemical, and physical agents by observing the molecular alterations in more detail. Toxicogenomics integrates classical toxicology with omics assays, thus allowing the characterization of the mechanism of action (MOA) of chemical compounds, novel small molecules, and engineered nanomaterials (ENMs). Lack of standardization in data generation and analysis currently hampers the full exploitation of toxicogenomics-based evidence in risk assessment. To fill this gap, TGx methods need to take into account appropriate experimental design and possible pitfalls in the transcriptomic analyses as well as data generation and sharing that adhere to the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. In this review, we summarize the recent advancements in the design and analysis of DNA microarray, RNA sequencing (RNA-Seq), and single-cell RNA-Seq (scRNA-Seq) data. We provide guidelines on exposure time, dose and complex endpoint selection, sample quality considerations and sample randomization. Furthermore, we summarize publicly available data resources and highlight applications of TGx data to understand and predict chemical toxicity potential. Additionally, we discuss the efforts to implement TGx into regulatory decision making to promote alternative methods for risk assessment and to support the 3R (reduction, refinement, and replacement) concept. This review is the first part of a three-article series on Transcriptomics in Toxicogenomics. These initial considerations on Experimental Design, Technologies, Publicly Available Data, Regulatory Aspects, are the starting point for further rigorous and reliable data preprocessing and modeling, described in the second and third part of the review series.
Author Pia Anneli Sofia Kinaret
Pia Anneli Sofia Kinaret,,
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, Angela Serra
Angela Serra,,
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, Antonio Federico
Antonio Federico,,
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, Pekka Kohonen
Pekka Kohonen,,
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, Penny Nymark
Penny Nymark,,
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, Irene Liampa
Irene Liampa,,
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, My Kieu Ha
My Kieu Ha,,
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, Jang-Sik Choi
Jang-Sik Choi,,
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, Karolina Jagiełło (FCh / DEChR / LECh)
Karolina Jagiełło,,
- Laboratory of Environmental Chemometrics
, Natasha Sanabria
Natasha Sanabria,,
-
et al.`
Journal seriesNanomaterials, ISSN 2079-4991, (N/A 70 pkt)
Issue year2020
Vol10
No4
Pages1-23
Publication size in sheets1.1
Article number750
Keywords in Englishtranscriptomics, toxicogenomics (TGx), high throughput, microarrays, sequencing, experimental design, engineered nanomaterials (ENM), toxicology, alternative risk assessment
DOIDOI:10.3390/nano10040750
URL https://doi.org/10.3390/nano10040750
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 15-04-2020, ArticleFromJournal
Publication indicators WoS Impact Factor: 2018 = 4.034 (2) - 2018=4.358 (5)
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