ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Identifying Attributes That Influence In Vitro-to-In Vivo Concordance by Comparing In Vitro Tox21 Bioactivity Versus In Vivo DrugMatrix Transcriptomic Responses Across 130 Chemicals.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Transcriptomic signature comparisons identify conserved key events and respiratory disease signatures most similar to wildfire-relevant exposure.Chemico-biological interactions · 2026Article
- Identifying Gene Predictors of Chemicals Linked With Breast Cancer: A Machine Learning Analysis of MCF7 Cellular Transcriptomic Screening Data.Environmental and molecular mutagenesis · 2025Article
- An uphill path to commercialization of silver nanoparticle antimicrobials: from bench to market.Nanomedicine (London, England) · 2025Article
- Extracellular Vesicle (EV) Mechanisms of Toxicity for Per and Polyfluoroalkyl Substances: Comparing Transcriptomic Points of Departure Across Global Versus EV Regulatory Gene Sets.Environmental and molecular mutagenesis · 2025Article
- Wildfire-relevant woodsmoke and extracellular vesicles (EVs): Alterations in EV proteomic signatures involved in extracellular matrix degradation and tissue injury in airway organotypic models.Environmental research · 2025Article
- Characterizing the extracellular vesicle proteomic landscape of the human airway usingiScience · 2023Article
- Bayesian matrix completion for hypothesis testing.Journal of the Royal Statistical Society. Series C, Applied statistics · 2023Article
- Wildfire Variable Toxicity: Identifying Biomass Smoke Exposure Groupings through Transcriptomic Similarity Scoring.Environmental science & technology · 2022Article
- Environmental mixtures and breast cancer: identifying co-exposure patterns between understudied vs breast cancer-associated chemicals using chemical inventory informatics.Journal of exposure science & environmental epidemiology · 2022Article
- Exposure forecasting - ExpoCast - for data-poor chemicals in commerce and the environment.Journal of exposure science & environmental epidemiology · 2022Review
- Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens.International journal of molecular sciences · 2022Review
- Wildfires and extracellular vesicles: Exosomal MicroRNAs as mediators of cross-tissue cardiopulmonary responses to biomass smoke.Environment international · 2022Article
- Integrative exposomic, transcriptomic, epigenomic analyses of human placental samples links understudied chemicals to preeclampsia.Environment international · 2022Article
- The placenta epigenome-brain axis: placental epigenomic and transcriptomic responses that preprogram cognitive impairment.Epigenomics · 2022Article
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- Development of the InTelligence And Machine LEarning (TAME) Toolkit for Introductory Data Science, Chemical-Biological Analyses, Predictive Modeling, and Database Mining for Environmental Health Research.Frontiers in toxicology · 2022Article
- Comparing the Predictivity of Human Placental Gene, microRNA, and CpG Methylation Signatures in Relation to Perinatal Outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Development of the genomic inflammatory index (GII) to assess key maternal antecedents associated with placental inflammation.Placenta · 2021Article
- Predictive modeling of biological responses in the rat liver usingComputational toxicology (Amsterdam, Netherlands) · 2021Article
- A role for microRNAs in the epigenetic control of sexually dimorphic gene expression in the human placenta.Epigenomics · 2020Article
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9 authors.
Funding
Abstract
Recent efforts aimed at integrating in vitro high-throughput screening (HTS) data into chemical toxicity assessments are necessitating increased understanding of concordance between chemical-induced responses observed in vitro versus in vivo. This investigation set out to (1) measure concordance between in vitro HTS data and transcriptomic responses observed in vivo, focusing on the liver, and (2) identify attributes that can influence concordance. Signal response profiles from 130 substances were compared between in vitro data produced through Tox21 and liver transcriptomic data through DrugMatrix, collected from rats exposed to a chemical for ≤5 days. A global in vitro-to-in vivo comparative analysis based on pathway-level responses resulted in an overall average percent agreement of 79%, ranging on a per-chemical basis between 41% and 100%. Whereas concordance amongst inactive chemicals was high (89%), concordance amongst chemicals showing in vitro activity was only 13%, suggesting that follow-up in vivo and/or orthogonal in vitro assays would improve interpretations of in vitro activity. Attributes identified to influence concordance included experimental design attributes (eg, cell type), target pathways, and physicochemical properties (eg, logP). The attribute that most consistently increased concordance was dose applicability, evaluated by filtering for experimental doses administered to rats that were within 10-fold of those related to likely bioactivity, derived using Tox21 data and high-throughput toxicokinetic modeling. Together, findings suggest that in vitro screening approaches to predict in vivo toxicity are viable particularly when certain attributes are considered, including whether activity versus inactivity is observed, experimental design, chemical properties, and dose applicability.
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