A Pipeline for High-Throughput Concentration Response Modeling of Gene Expression for Toxicogenomics. Academic Article uri icon


  • Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression profiling for in vitro toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation. Analyses of high-throughput toxicogenomics data require renewed attention to read-calling algorithms and simplified dose-response modeling for datasets with relatively few samples. Using data from induced pluripotent stem cell-derived cardiomyocytes treated with chemicals at varying concentrations, we describe here and make available a pipeline for handling expression data generated by TempO-Seq to align reads, clean and normalize raw count data, identify differentially expressed genes, and calculate transcriptomic concentration-response points of departure. The methods are extensible to other forms of concentration-response gene-expression data, and we discuss the utility of the methods for assessing variation in susceptibility and the diseased cellular state.

published proceedings

  • Front Genet

altmetric score

  • 1.25

author list (cited authors)

  • House, J. S., Grimm, F. A., Jima, D. D., Zhou, Y., Rusyn, I., & Wright, F. A.

citation count

  • 38

complete list of authors

  • House, John S||Grimm, Fabian A||Jima, Dereje D||Zhou, Yi-Hui||Rusyn, Ivan||Wright, Fred A

publication date

  • November 2017