Simplicity: Web-Based Visualization and Analysis of High-Throughput Cancer Cell Line Screens

Abstract

High-throughput drug screens are a powerful tool for cancer drug development. However, the results of such screens are often made available only as raw data, which is intractable for researchers without informatics skills, or as highly processed summary statistics, which can lack essential information for translating screening results into clinically meaningful discoveries. To improve the usability of these datasets, we developed Simplicity, a robust and user-friendly web interface for visualizing, exploring, and summarizing raw and processed data from high- throughput drug screens. Importantly, Simplicity allows for easy recalculation of summary statistics at user-defined drug concentrations. This allows Simplicity's outputs to be used with methods that rely on statistics being calculated at clinically relevant doses. Simplicity can be freely accessed at https://oncotherapyinformatics.org/simplicity/.

Keywords: Cancer; Computational biology; Drug repurposing; High-throughput drug screens; Simplicity.

Figure 1:

Example functionality of Simplicity. Plots, tables, and interfaces from Simplicity. (A) Ancestry plot for glioblastoma (GBM) cell lines tested with 5-Fluorouracil in GDSC1 as provided by the “Data Explorer/Explore Compounds” tab. (B) Examples of drug and cell-line level summaries produced by Simplicity. Left panel: Plot showing measured sensitivities (IC50s) of Tozasertib in GBM cell lines in the PRISM-Repurposing dataset as provided by the “Data Explorer/Explore Compounds” tab. Cell lines names and exact IC50 values can be obtained by hovering over each data point. Right panel: Plot showing relative sensitivity of NKM-1 cell line to FDA approved (Launched) compounds tested in GDSC2 as measured by IC50 percentile relative to all other cell lines tested with each compound in GDSC2 as provided by the “Data Explorer/Explore Cell Lines” tab. Higher percentiles indicate NKM-1 was more sensitive to a given compound relative to other tested lines. Direct IC50 values can be obtained by hovering over each data point or by downloading the summary statistics tables provided in the “Download Bulk Data” tab of Simplicity. Note that infinite IC50 values occur when fitted dose-response curves have a lower asymptote above 50% viability. This can occur when the data directly implies an asymptote above 50% viability or when the tested compound shows no efficacy at any tested dose such that the fitted dose response curve is simply a flat line at 100% viability. (C) Calculated dose-response curves for cisplatin in the NKM-1 cell line in both GDSC1 and GDSC2 along with the experiment IDs used to calculate the curves as provided by the “Data Explorer/Plot Dose-Response Curves” tab. (D) Table of experimental conditions used in the experiments shown in panel C as provided by the “Data Explorer/Plot Dose-Response Curves” tab. (E) User interface for calculating viability values at specified concentrations. The interface allows users to easily select compounds, cell lines, and concentrations of interest using a graphical user interface. A similar interface is also available for calculating area under the curve (AUC) values at custom concentration ranges.