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CalDyn: an advanced high-throughput automated algorithm for monitoring intracellular calcium dynamics and electrophysiological signals in patient-derived cells

Year: 2026

Type: article

Abstract: BACKGROUND: Quantitative analysis of intracellular calcium and electrophysiological signals is challenging when signals exhibit baseline drift, low-amplitude events, irregular waveforms, or multicomponent transients. We developed CalDyn, a MATLAB-based graphical application for automated peak detection, waveform characterization, event classification, batch processing, quality control and data export. METHODS: CalDyn combines Savitzky-Golay filtering, LOESS-assisted derivative detection, optional baseline correction, waveform-boundary fitting and rule-based peak classification. It was evaluated on calcium recordings (healthy and disease-associated hiPSC-derived cardiomyocytes, hiPSC-derived neurons, primary skeletal myotubes), current-clamp action potentials and cardiac optical-mapping signals. Outputs were compared with PeakInspector, Clampfit and BV Workbench using paired and Bland-Altman analyses. Detection was assessed against 142 expert-annotated events and synthetic signals of known timing and amplitude. RESULTS: CalDyn achieved 94.4% sensitivity, 89.9% precision and an F1 score of 0.92. Performance peaked for healthy cardiomyocytes, paced myotubes and action potentials, with lower recall in arrhythmic cardiomyocytes and variable precision in neurons. CalDyn detected candidate low-amplitude diastolic and multicomponent Ca2+ events in arrhythmic cardiomyocytes, although the biological identity of CalDyn-only events was not independently confirmed. Comparisons with software revealed parameter-specific systematic differences, notably for rise rates and classifications. Action-potential measurements showed limited mean bias but non-negligible limits of agreement. In synthetic signals, amplitude error increased with noise and uncorrected drift, and timing error with low sampling rates. Detection remained stable across moderate parameter variation. CONCLUSIONS: CalDyn provides an accessible, reproducible and versatile workflow for automated analysis of heterogeneous calcium and electrophysiological signals. With appropriate quality control, it offers a robust alternative to modality-specific tools.

Source: Briefings in Bioinformatics

DOI: 10.1093/bib/bbag602