A Robust Data Analysis Workflow for Highly Scalable, Routine Application of Calcium Oscillation Assays

SLAS, San Diego, CA, USA
February 27, 2023

Calcium (Ca²⁺) signalling forms the basis of many physiological and pathological functions, due to Ca²⁺-mediated signaling being central to many signal transduction pathways. As one example, the dysregulation of calcium-dependent pathways can result in neurological disorders like Parkinson’s disease. In another example, the plethora of ion channels in cardiomyocytes makes them a significant potential safety liability for any potential new drug; off-target effects such as hERG channel block, detectable in Ca2+ oscillation experiments, can cause adverse symptoms like Torsades de Pointes. Therefore, Ca²⁺ oscillation assays—particularly, those using induced pluripotent stem cell (iPSC)- derived cardiomyocytes or neurons—are essential tools in the discovery of drugs against several neurological disorders and in assessing cardiac safety of drug candidates. The availability of these new assays enables relatively high throughput screening, making data analysis the next performance bottleneck. Herein, we present a new workflow in Genedata Screener^® for automated, high-throughput analysis of Ca²⁺ oscillation data. It allows parallel processing of all wells of a screening run, where the parametrization is automatically adjusted to the individual measurements and allows characterization of a diverse set of recorded responses. It also offers a set of quality control output observables that can be included in the downstream analysis, e.g., flagging of ‘silent’ periods in corresponding recordings. We present the workflow components, highlight its automation features, and discuss its impact on Axxam‘s screening portfolio.