SPARCS, published in Cell, links complex microscopy phenotypes to genes across ~70M cells
jiqizhixin · x · 2026-10-18
Researchers at LMU Munich and the Max Planck Institute of Biochemistry present SPARCS (Spatially-resolved CRISPR Screening), published in Cell on October 6, 2026.
- Problem solved: genome-wide CRISPR screens can perturb every gene, but when the phenotype is a complex microscopy image rather than a simple survival/fluorescence readout, linking image-level cellular changes to specific genes has been a long-standing bottleneck.
- Approach: ML-driven microscopy image analysis combined with automated cell recovery. Mutant cell libraries are plated on PPS membranes, imaged, segmented into single cells, grouped by similar spatial phenotypes, then recovered via laser microdissection (LMD) or FACS followed by sgRNA sequencing.
- Scale: two genome-wide CRISPR knockout screens analyzing 70 million cells total, studying autophagosome formation and innate immune activation.
The figure validates that LMD and FACS recovery paths yield comparable sgRNA recovery (p=0.5135), a full workflow for AI-driven functional genomics.
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