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Updated: Jun 6, 2026

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning
Published on: March 3, 2023
Deep learning of functional perturbations from condensate morphology
Anita Donlic1, Troy J Comi2, Sofia A Quinodoz3
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA.
Abstract:
Biomolecular condensates compartmentalize the interior of cells to organize complex functions, yet linking molecular interactions within condensates to their mesoscale organization remains a major challenge. To bridge this gap, we developed a neural-network-based framework-Deep-Phase (deep learning of phase-separated condensates)-that uses microscopy images to directly measure condensate morphology changes resulting from pharmacological alterations in associated biochemical processes. We use Deep-Phase to precisely quantify time- and concentration-dependent structural perturbations to the multiphase nucleolus and show that they are tightly coupled to potencies of drugs inhibiting ribosomal RNA (rRNA) transcription and processing. Applying Deep-Phase in a chemical screen, we identify a unique nucleolar morphology and discover a role for a DNA topoisomerase in rRNA processing. Mechanistic studies of this morphology provide insights into how the interfaces between nucleolar sub-compartments are maintained. We demonstrate Deep-Phase's adaptability to diverse cell lines, labeling techniques, and condensates, offering a powerful platform for connecting molecular pathways to cellular mesoscale organization.
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