Development of the Theta-Comparative-Cell-Scoring (TCCS) Method to Quantify Diverse Phenotypic Responses between Distinct Cell Types

Scott Warchal, John Dawson, Neil Carragher

Research output: Contribution to journalArticlepeer-review

Abstract

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 identification of biomarkers and further elucidate drug mechanism-of-action. Application of these methods to compound profiling across high-content 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.
Original languageEnglish
JournalAssay and Drug Development Technologies
Volume14
Issue number7
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Analysis
  • Imaging
  • Informatics
  • Cell biology
  • Cancer

Fingerprint

Dive into the research topics of 'Development of the Theta-Comparative-Cell-Scoring (TCCS) Method to Quantify Diverse Phenotypic Responses between Distinct Cell Types'. Together they form a unique fingerprint.

Cite this