Development of the Theta Comparative Cell Scoring Method to Quantify Diverse Phenotypic Responses Between Distinct Cell Types

Scott J. Warchal, John C. Dawson, Neil O. Carragher
2016 Assay and drug development technologies  
In this article, we have developed novel data visualization tools and a Theta comparative cell scoring (TCCS) method, which supports high-throughput in vitro pharmacogenomic studies across diverse cellular phenotypes measured by multiparametric high-content analysis. The TCCS method provides a univariate descriptor of divergent compound-induced phenotypic responses between distinct cell types, which can be used for correlation with genetic, epigenetic, and proteomic datasets to support the
more » ... ification of biomarkers and further elucidate drug mechanism-of-action. Application of these methods to compound profiling across highcontent assays incorporating well-characterized cells representing known molecular subtypes of disease supports the development of personalized healthcare strategies without prior knowledge of a drug target. We present proof-of-principle data quantifying distinct phenotypic response between eight breast cancer cells representing four disease subclasses. Application of the TCCS method together with new advances in next-generation sequencing, induced pluripotent stem cell technology, gene editing, and high-content phenotypic screening are well placed to advance the identification of predictive biomarkers and personalized medicine approaches across a broader range of disease types and therapeutic classes.
doi:10.1089/adt.2016.730 pmid:27552144 pmcid:PMC5015429 fatcat:n25juqj5abbg7mpp4g5txrzwry