Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver and Cultured Hepatocytes
Pairs of experiments involving the same drug are compared via the Pearson R and percent overlap metrics, and average concordance is calculated between TG rat liver (reference set) and A) TG rat liver (within-source), B) DM rat liver (cross-source) and C) GEO mouse liver (cross-source and cross-species). Concordance is shown additively for 3 levels of constraint on dose and time differences: experiments at the same time point and doses within 5 fold (pink), time within 2 fold and doses within 10 fold (blue), no constraint on doses or time (green). In each case, experiments are compared to TG rat liver and the most concordant experiment selected within the level of constraint. Only experiments that have a match to TG rat liver at the most constrained level are considered at the other levels. Because concordance can only improve upon removing dose and time constraints, results are shown additively with the total bar height denoting the concordance achieved with no constraints. Numeric values represent the probability that the given level of concordance exceeds that of random pairs involving different drugs for the most stringent level considered (pink bars). Experiment pairs are separated into 3 ranges based on the level of transcriptional activity for the least perturbing of two treatments (lowest quartile have avg. abs. EG ≤ 0.28, highest quartile have avg. abs. EG > 0.46; thresholds selected using 3528 TG rat liver experiments).