Concinnity
We built a directional readout of organelle dynamics.
Core trick
Building and clearing gene programs are scored separately and subtracted, so the signed difference reads direction rather than organelle amount.
Description
We built a directional readout of organelle dynamics. Standard analysis measures how much of an organelle is present - it can't separate a cell building an organelle up from one blocking its clearance, and the clearance genes (selective-autophagy receptors like BNIP3) aren't in conventional organelle signatures. We score the building and clearing programs separately and subtract: one signed number whose sign is the biology.
What we found: reading direction, not amount, predicts mitochondrial vulnerability in cancer. Across 1,066 DepMap cell lines, higher mito-biogenesis direction means stronger genetic dependency on that machinery (ρ=−0.35, p=1.7×10⁻³²) - and it's specific (the same test on ribosomes is null). From expression alone it also ranks drug response: the clinical Complex-I inhibitor IACS-010759 lands in the top 3% of 1,514 drugs, and MitoQ ranks #1. Direction beats amount on the vulnerability endpoint (AUROC 0.67 vs 0.61).
Why it matters: OXPHOS-targeting cancer drugs keep stalling on patient selection - no one can tell in advance which tumors depend on their mitochondria. This reads exactly that, from data already collected.
Honest bounds: effect sizes are modest, the cancer results are in cell lines, and our one patient-survival test (TCGA-KIRC, 510-tumor cohort) is a clean null at power - reported. All public data.
different-change/organelle-direction★ 00 forksHTMLNOASSERTIONCreated Jul 13, 2026 · last push Oct 21, 2026
README excerpt
<div align="center"> # Organelle Direction ### Same amount. Opposite fate. **Two cells can hold the same number of mitochondria for opposite reasons — one is building them, the other has stopped clearing them. Count how many are there and they look identical. Read the *direction* instead, and you can predict which cancers are addicted to their mitochondria, and which drugs will hit them.** [**▶ Open the interactive demo**](https://different-change.github.io/organelle-direction/) · [**Read the report**](https://different-change.github.io/organelle-direction/report/report.html) · [**Full technical record**](https://different-change.github.io/organelle-direction/report/full_technical_report.html) [](LICENSE) [](LICENSE) [](#how-claude-science-was-used) [](#data-sources-all-public) </div> --- ## The one idea A standard organelle signature answers *how much is there*. But build-up and tear-down move many of the same genes, so a single-axis score cannot tell a cell that is proliferating mitochondria from one whose disposal machinery has stalled. To the cell those are opposite states. Worse, the genes that *would* separate them — the selective-auto