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Contact UsCellCiphr® Profiles and Classifier – Identify Potential Toxicants Early in Drug Discovery
CellCiphr® Profiles is a data mining tool that compares key toxicity system responses in tissue specific cell models. CellCiphr® Profiles tabulate and display multiplexed cell, feature, time and concentration dependent profiles.
Data flow from image to compound profile. (A) The images, here depicting increasing green signal, are used to generate the dose response curve and calculate the AC50 for one cell feature. The AC50 values from the 30 cell feature set are tabulated (B) and used to build the CellCiphr® Profile (C).
Toxicity system responses are correlated using the CellCiphr® Classifier Analysis Tool. The classifier algorithm applies the panel assay results to calculate compound toxicity at several levels of detail to interpret cellular toxicity by:
- Calculating the maximal tolerated dose
- Identifying the earliest and most sensitive indicators of cellular functional effects
- Drawing rule-based AC50 (activity concentration) curves for each parameter
- Identifying common modes of activity in a lead series
- Discovering clusters of compounds with similar activity profiles
- Correlating compound profile similarity to known toxic control profiles
- Calculating rank order and safety risks for compound prioritization
CellCiphr® Classifier provides several visual and tabulated responses to make informed decisions on lead series compounds. The CellCiphr® Classifier tool provides similarity scores to our ever-increasing database of known controls and to other compounds in a test series. Heat maps and similarity scoring are useful to set testable hypotheses to identify possible mechanisms of action.
CellCiphr® Classifier clusters compounds by similarity of toxicity profiles, and is illustrated as a heat map of responses from a library of controls.
CellCiphr® Profiles are used to identify common similarities to other series compounds (blue line) and to known profile controls (red line). Detailed comparisons of CellCiphr® Profiles for a lead series indicate precise differences in cellular actions to controls and to other compounds.
The CellCiphr® Classifier analysis tool provides several tabular summaries of the screen results. These summaries are useful to identify the earliest and the most potent cell feature response which is information that can be used to determine a single, reliable end-point assay for an extensive SAR campaign.
The earliest and most potent compound activities vary across cell features and time points. The Classifier tool can be used to calculate the rank order of compounds against the universe of all compounds or within a selected series set of compounds. The rank order is useful to prioritize compounds for additional follow-on studies or pre-clinical candidacy. Finally, a first generation classifier safety risk index is provided that has been shown to identify 100% of the significantly toxic compounds. Even more advanced Classifiers are in development.
Example of rank order and safety risk index calculated using the CellCiphr® Classifier.
A final Profiling Report conveniently summarizes:
- All 30-feature dose-response curves with best curve fit
- All AC50 calculations
- Earliest and most sensitive cell feature responses
- General measurements of toxicity
- Similarity plots and correlations to compounds in a series and to control compounds
- Rank order within a group of defined compounds
- Safety Index with high correlation to in vivo toxicity
Example of part of the CellCiphr® final Profiling Report
CellCiphr® Toxicity Profiling establishes a reliable basis for prioritizing lead compounds early in the development process.
CellCiphr® Toxicity Profiling identifies potential toxicants before entering expensive pre-clinical testing. Contact us to learn more.