# Ali Chegini

- **Event:** [Built with Claude: Life Sciences](https://cerebralvalley.ai/e/built-with-claude-life-sciences)
- **When:** Jul 7 at 12:00 PM – Jul 14 at 12:00 AM (EDT)
- **Where:** Online
- **Team:** [Ali Chegini](https://cerebralvalley.ai/u/AliChegini)
- **GitHub:** https://github.com/AliChegini97/Built-with-Claude-Life-Sciences.git              https://github.com/AliChegini97/aars-cyto-mito-similarity.git
- **Demo video:** https://youtu.be/qwAC-gHnGkI
- **Gallery:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery
- **Page:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/281

**Project description**

This repository is the **computational side** of a PhD thesis (Schimmer lab, U of T Medical Biophysics): *Identifying Variable Dependencies in the Mitochondrial Proteome in AML.* The goal is to find genes that are **variably essential** — lethal in only a *subset* of AML myeloid cell lines rather than pan-essential — from DepMap CRISPR gene-effect screens, then follow the biology.

**Built:** a variability engine (apps/DepMapVariablyEssential/) that scores selective essentiality across several algorithms (Static, Dynamic, the PCA/RPCA/PPCA families, Likelihood1D, plus ML classifiers), with a posterior decision-boundary framework and GO/MitoCarta3/Reactome pathway-GSEA. A core methodological point: raw variance ≠ selective essentiality — pan-essential genes swinging between "death and more death" look variable but aren't real vulnerabilities; a true hit must *cross* the essential/non-essential boundary. The pipeline was also made deterministic (exact SVD, seeded PPCA, sorted intersections).

**Found:** the leading hits converge on **mitochondrial translation** — the mitoribosome and mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) — with **RARS2** as the flagship gene and YARS2/FARS2/EARS2/NARS2 as the validation panel.

**Why it matters:** selective dependencies are candidate AML therapeutic targets that spare cells lacking the vulnerability; wet-lab validation follows.

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