GRcalculator

GRcalculator computes normalized growth rate (GR) metrics to analyze and compare dose-response data, mitigating confounding from cell division rate variability to improve reproducibility in pharmacogenomic and pre-clinical drug-response studies.

Key Features:

• Normalized Growth Rate (GR) Methodology: Implements the GR approach of Hafner et al. to quantify drug response via GR inhibition and reduce bias from variable cell division rates.
• Comparison with Traditional Metrics: Facilitates direct comparison between GR metrics and traditional dose-response metrics including IC50, AUC, and Emax.
• Data Handling: Accepts user-supplied datasets and published datasets such as those from the NIH LINCS program for analysis.
• Software Integration: Implements computation through R packages shinyLi and GRmetrics, with GRmetrics available via Bioconductor for integration into R pipelines.
• Analytical Outputs: Produces GR inhibition calculations and dose-response visualizations for downstream analysis.
• Perturbagen and Cell-Type Applicability: Applicable to diverse cell types and perturbagens including small-molecule drugs, biological ligands, and RNA interference.

Scientific Applications:

• Pre-Clinical Drug Development: Enables assessment of drug efficacy and resistance mechanisms using GR-corrected dose-response metrics.
• Pharmacogenomics: Supports studies linking genetic variation to differential drug response using GR-normalized measurements.
• General Perturbation Studies: Applicable to analysis of cellular responses across diverse perturbagens and cell types for comparative studies.

Methodology:

Computes normalized growth rate (GR) metrics and GR inhibition according to Hafner et al., compares GR metrics to IC50/AUC/Emax, and implements analyses using the R packages shinyLi and GRmetrics (GRmetrics available on Bioconductor).