Mapping Biological Pathways Using Systematic Genetics and Cell Biology

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Systematic double-mutant mapping uses synthetic genetic array (SGA) and a colony size fitness proxy to quantify genetic interactions in yeast and yields ~1 million interactions (≈550k negative, 350k positive) including ~10k synthetic lethal pairs. Principles guide CRISPR/Cas9 screens in HAP1 cells: 108 query lines produce ~3 million double mutants and ~80k interactions that cluster into bioprocess modules. Conserved motifs link PTAR1/ECM9 to vesicle trafficking, revealing a palmitoyltransferase suppressor and human depalmitoylase hits. Single-cell imaging with Gaussian mixture outlier detection is developed but remains analytically challenging.

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" chapters (11)

1. 0:00Introduction to GINs
2. 1:35Yeast GIN methodology
3. 3:56Interpreting network data
4. 6:15Functional network insights
5. 9:52Expanding to human cells
6. 12:41HAP1 screening pipeline
7. 16:02Human network architecture
8. 18:24Mechanistic case studies
9. 21:04Single cell imaging
10. 24:16Computational analysis
11. 26:21Q&A and discussion