FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3136156118> ?p ?o ?g. }

• W3136156118 endingPage "100166" @default.
• W3136156118 startingPage "100166" @default.
• W3136156118 abstract "Computational methods are needed to more efficiently leverage data from in vitro cell-based models to predict what occurs within whole body systems after chemical insults. This study set out to test the hypothesis that in vitro high-throughput screening (HTS) data can more effectively predict in vivo biological responses when chemical disposition and toxicokinetic (TK) modeling are employed. In vitro HTS data from the Tox21 consortium were analyzed in concert with chemical disposition modeling to derive nominal, aqueous, and intracellular estimates of concentrations eliciting 50% maximal activity. In vivo biological responses were captured using rat liver transcriptomic data from the DrugMatrix and TG-Gates databases and evaluated for pathway enrichment. In vivo dosing data were translated to equivalent body concentrations using HTTK modeling. Random forest models were then trained and tested to predict in vivo pathway-level activity across 221 chemicals using in vitro bioactivity data and physicochemical properties as predictor variables, incorporating methods to address imbalanced training data resulting from high instances of inactivity. Model performance was quantified using the area under the receiver operator characteristic curve (AUC-ROC) and compared across pathways for different combinations of predictor variables. All models that included toxicokinetics were found to outperform those that excluded toxicokinetics. Biological interpretation of the model features revealed that rather than a direct mapping of in vitro assays to in vivo pathways, unexpected combinations of multiple in vitro assays predicted in vivo pathway-level activities. To demonstrate the utility of these findings, the highest-performing model was leveraged to make new predictions of in vivo biological responses across all biological pathways for remaining chemicals tested in Tox21 with adequate data coverage (n = 6617). These results demonstrate that, when chemical disposition and toxicokinetics are carefully considered, in vitro HT screening data can be used to effectively predict in vivo biological responses to chemicals." @default.
• W3136156118 created "2021-03-29" @default.
• W3136156118 creator A5009660240 @default.
• W3136156118 creator A5013677882 @default.
• W3136156118 creator A5014849102 @default.
• W3136156118 creator A5015966096 @default.
• W3136156118 creator A5052171006 @default.
• W3136156118 creator A5071242863 @default.
• W3136156118 creator A5072625370 @default.
• W3136156118 creator A5074912970 @default.
• W3136156118 creator A5081432746 @default.
• W3136156118 date "2021-05-01" @default.
• W3136156118 modified "2023-09-27" @default.
• W3136156118 title "Predictive modeling of biological responses in the rat liver using in vitro Tox21 bioactivity: Benefits from high-throughput toxicokinetics" @default.
• W3136156118 cites W1563656983 @default.
• W3136156118 cites W1835137027 @default.
• W3136156118 cites W1903630402 @default.
• W3136156118 cites W1984428215 @default.
• W3136156118 cites W2006617902 @default.
• W3136156118 cites W2023813192 @default.
• W3136156118 cites W2035585921 @default.
• W3136156118 cites W2045967218 @default.
• W3136156118 cites W2047195343 @default.
• W3136156118 cites W2088402748 @default.
• W3136156118 cites W2099536383 @default.
• W3136156118 cites W2106502953 @default.
• W3136156118 cites W2112058534 @default.
• W3136156118 cites W2130410032 @default.
• W3136156118 cites W2144227498 @default.
• W3136156118 cites W2144486134 @default.
• W3136156118 cites W2146512944 @default.
• W3136156118 cites W2148143831 @default.
• W3136156118 cites W2167778120 @default.
• W3136156118 cites W2225235469 @default.
• W3136156118 cites W2260565828 @default.
• W3136156118 cites W2314745102 @default.
• W3136156118 cites W2397394044 @default.
• W3136156118 cites W2425280153 @default.
• W3136156118 cites W2555601680 @default.
• W3136156118 cites W2560627368 @default.
• W3136156118 cites W2562319768 @default.
• W3136156118 cites W2567231876 @default.
• W3136156118 cites W2597381050 @default.
• W3136156118 cites W2611052709 @default.
• W3136156118 cites W2625449182 @default.
• W3136156118 cites W2734700870 @default.
• W3136156118 cites W2745718614 @default.
• W3136156118 cites W2751320415 @default.
• W3136156118 cites W2755867701 @default.
• W3136156118 cites W2791653123 @default.
• W3136156118 cites W2887896328 @default.
• W3136156118 cites W2890392630 @default.
• W3136156118 cites W2890575526 @default.
• W3136156118 cites W2911964244 @default.
• W3136156118 cites W2947336471 @default.
• W3136156118 cites W2951027420 @default.
• W3136156118 cites W2959681374 @default.
• W3136156118 cites W2963921098 @default.
• W3136156118 cites W2973521279 @default.
• W3136156118 cites W2985881898 @default.
• W3136156118 cites W2994753422 @default.
• W3136156118 cites W3012561843 @default.
• W3136156118 cites W3121495924 @default.
• W3136156118 cites W3136156118 @default.
• W3136156118 doi "https://doi.org/10.1016/j.comtox.2021.100166" @default.
• W3136156118 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8130852" @default.
• W3136156118 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34013136" @default.
• W3136156118 hasPublicationYear "2021" @default.
• W3136156118 type Work @default.
• W3136156118 sameAs 3136156118 @default.
• W3136156118 citedByCount "27" @default.
• W3136156118 countsByYear W31361561182021 @default.
• W3136156118 countsByYear W31361561182022 @default.
• W3136156118 countsByYear W31361561182023 @default.
• W3136156118 crossrefType "journal-article" @default.
• W3136156118 hasAuthorship W3136156118A5009660240 @default.
• W3136156118 hasAuthorship W3136156118A5013677882 @default.
• W3136156118 hasAuthorship W3136156118A5014849102 @default.
• W3136156118 hasAuthorship W3136156118A5015966096 @default.
• W3136156118 hasAuthorship W3136156118A5052171006 @default.
• W3136156118 hasAuthorship W3136156118A5071242863 @default.
• W3136156118 hasAuthorship W3136156118A5072625370 @default.
• W3136156118 hasAuthorship W3136156118A5074912970 @default.
• W3136156118 hasAuthorship W3136156118A5081432746 @default.
• W3136156118 hasBestOaLocation W31361561181 @default.
• W3136156118 hasConcept C104317684 @default.
• W3136156118 hasConcept C107908354 @default.
• W3136156118 hasConcept C112705442 @default.
• W3136156118 hasConcept C150903083 @default.
• W3136156118 hasConcept C164126121 @default.
• W3136156118 hasConcept C185592680 @default.
• W3136156118 hasConcept C186060115 @default.
• W3136156118 hasConcept C195289149 @default.
• W3136156118 hasConcept C202751555 @default.
• W3136156118 hasConcept C207001950 @default.
• W3136156118 hasConcept C2775905019 @default.
• W3136156118 hasConcept C33618052 @default.
• W3136156118 hasConcept C55493867 @default.

• next