Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies

Abstract

The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to uncover commonalities between in vitro and in vivo observations on the cellular level. Using a literature mining strategy, we identified 1221 unique human genes as being associated to nephrotoxicity, hepatotoxicity, or CNS toxicity, either linked to in vitro, in vivo, or both experimental conditions. Among this large set of relevant molecular features four genes were found in common to all tissues and experimental conditions analyzed, namely heme oxygenase-1, nitric oxide synthetase 2, NFκB1 and p53. Pathway enrichment revealed 17 relevant pathways for kidney, 26 for liver, and 30 for CNS bridging in vitro and in vivo toxicity effects. Such joint markers and pathways may serve as indicators for extrapolating from in vitro results to in vivo.