BeatVecNet classifies drug-induced contractile phenotypes from beat-gated motion vectors in micropatterned human induced pluripotent stem cell-derived cardiomyocytes.

Abstract

Background and purpose: Assessment of electrophysiological cardiotoxicity in vitro has advanced, yet scalable assays for contractile dysfunction remain limited. BeatVecNet, an interpretable deep-learning framework, classifies drug-induced contractile phenotypes from beat-gated motion vectors in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Experimental approach: BeatVecNet was developed and evaluated using beat-gated motion-vector tensors derived from hiPSC-CMs recorded by label-free phase-contrast imaging at 150 fps. hiPSC-CMs were cultured on micropatterned substrates to provide a consistent contraction axis for directional motion analysis. Dense optical flow was used to derive motion vectors, which were retained as beat-gated spatiotemporal tensors rather than reduced to scalar traces. The model uses two convolutional branches to process horizontal and vertical velocity components separately and was evaluated on independent assays containing control, doxorubicin, trastuzumab and sunitinib.

Key results: BeatVecNet distinguished drug-induced contractile phenotypes with a macro-F1 of 0.916, outperforming conventional kinematic classifiers (best baseline 0.706), with the largest advantage at low doses. Branch-replacement ablation indicated non-redundant contributions of horizontal and vertical motion components, with trastuzumab classification showing greater sensitivity to horizontal-component replacement and sunitinib classification to vertical-component replacement. Phase-resolved attribution further identified temporal patterns within the beat cycle not explained by peak velocity alone. Micropatterning improved signal consistency and contractile coherence, enabling robust directional motion analysis.

Conclusion and implications: BeatVecNet extracts drug-associated contractile signatures not captured by conventional scalar analysis while providing direction- and phase-resolved interpretability at the motion-representation level. This platform complements electrophysiology-centred safety assessment and provides proof of concept for classification of subtle drug-induced contractile phenotypes.