A transcriptomics data-driven gene space accurately predicts liver cytopathology and drug-induced liver injury

Pekka Kohonen, Juuso A. Parkkinen, Egon L. Willighagen, Rebecca Ceder, Krister Wennerberg, Samuel Kaski, Roland C. Grafström*

*Tämän työn vastaava kirjoittaja

Tutkimustuotos: LehtiartikkeliArticleScientificvertaisarvioitu

39 Sitaatiot (Scopus)
180 Lataukset (Pure)

Abstrakti

Predicting unanticipated harmful effects of chemicals and drug molecules is a difficult and costly task. Here we utilize a 'big data compacting and data fusion' - concept to capture diverse adverse outcomes on cellular and organismal levels. The approach generates from transcriptomics data set a 'predictive toxicogenomics space' (PTGS) tool composed of 1,331 genes distributed over 14 overlapping cytotoxicity-related gene space components. Involving ∼2.5 × 108 data points and 1,300 compounds to construct and validate the PTGS, the tool serves to: explain dose-dependent cytotoxicity effects, provide a virtual cytotoxicity probability estimate intrinsic to omics data, predict chemically-induced pathological states in liver resulting from repeated dosing of rats, and furthermore, predict human drug-induced liver injury (DILI) from hepatocyte experiments. Analysing 68 DILI-annotated drugs, the PTGS tool outperforms and complements existing tests, leading to a hereto-unseen level of DILI prediction accuracy.

AlkuperäiskieliEnglanti
Artikkeli15932
Sivut1-15
JulkaisuNature Communications
Vuosikerta8
DOI - pysyväislinkit
TilaJulkaistu - 3 heinäkuuta 2017
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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