AUTHOR=House John S. , Grimm Fabian A. , Jima Dereje D. , Zhou Yi-Hui , Rusyn Ivan , Wright Fred A. 

TITLE=A Pipeline for High-Throughput Concentration Response Modeling of Gene Expression for Toxicogenomics

JOURNAL=Frontiers in Genetics

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2017.00168

DOI=10.3389/fgene.2017.00168

ISSN=1664-8021

ABSTRACT=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 requires 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.