# Meow

- **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:** [Shanshan Yin](https://cerebralvalley.ai/u/Shirlay)
- **GitHub:** https://github.com/shanshan-yin/Claude-Science-T-cell-pertubseq-melanoma-ICB https://raw.githack.com/shanshan-yin/Claude-Science-T-cell-pertubseq-melanoma-ICB/main/websites/index.html
- **Demo video:** https://youtu.be/htTqtNN_LVY
- **Gallery:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery
- **Page:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/43

Immune checkpoint blockade (ICB) reactivates T cells to kill tumors and has transformed cancer treatment, but many patients don't respond. Most work on ICB response has focused on CD8⁺ killer T cells, but emerging evidence shows the CD4⁺ helper T cell is also important. Focusing on CD4⁺ helper T cells, I asked which gene-regulatory pathways push them into a non-responding state, and whether those pathways are druggable. I compared CD4 T cells from responders and non-responders in single-cell RNA-seq of 32 melanoma patients to define a non-responder signature, then integrated a genome-scale Perturb-seq atlas of ~2,600 gene knockdowns in healthy-donor CD4 T cells. Because each knockdown is a direct perturbation, the model learns which regulators causally push cells toward responding or non-responding, not merely what correlates. A model trained on the resting-condition perturbation data reproduced the patient signature well, and the top knockdowns cluster into coherent pathways. The interferon pathway was the highest-ranked controller of the response state, and its downstream genes are upregulated in non-responders — so inhibiting interferon should push cells toward responding. Critically, interferon-receptor antibodies and JAK inhibitors are already-approved interferon-pathway inhibitors, turning the analysis into a concrete, testable hypothesis to sensitize non-responders.

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Markdown version of https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/43. Site index for agents: https://cerebralvalley.ai/llms.txt · full text: https://cerebralvalley.ai/llms-full.txt