Geometric coherence of single-cell CRISPR perturbations reveals regulatory architecture and predicts cellular stress

Researchers introduced Shesha, a metric for directional coherence in single-cell CRISPR responses.

Across multiple datasets, Shesha tracked effect size but also separated distinct regulatory programs.

It linked geometric instability to cellular stress and highlighted regulators such as CEBPA, GATA1, KLF1, and HSPA5/BiP.

The approach adds a new way to judge CRISPR perturbations by asking whether cells move in a coordinated direction, improving hit screening and biological interpretation.