RT Journal Article
SR Electronic
T1 A normalized drug response metric improves accuracy and consistency of drug sensitivity quantification in cell-based screening
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 262568
DO 10.1101/262568
A1 Abhishekh Gupta
A1 Prson Gautam
A1 Krister Wennerberg
A1 Tero Aittokallio
YR 2018
UL http://biorxiv.org/content/early/2018/02/08/262568.abstract
AB Accurate and robust quantification of drug effects is crucial for identifying pharmaceutically actionable cancer vulnerabilities. Current cell viability-based measurements often lead to biased response estimates due to varying cell growth rates and experimental artifacts, including background noise and cell seeding discrepancies, that explain part of the inconsistency in high-throughput screening results. To address these limitations, we developed an improved drug scoring model, normalized drug response (NDR), which accounts for differences in cell growth rates and experimental noise, and considers both positive and negative control conditions to characterize drug-induced effects. We demonstrate an improved performance of NDR compared to existing metrics in assessing drug responses of cancer cells in various culture models. Notably, NDR reliably differentiates a wider spectrum of drug behavior, including lethal, growth-inhibitory and growth-stimulatory modes, based on a single viability readout. The method will therefore substantially reduce the time and resources required in cell-based drug sensitivity screening.