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CREative

To understand how Alzheimer’s disease reshapes the brain’s regulatory landscape cell type by cell type, I used Claude Science to analyze Droplet Paired-Tag data from 10 donors across the hippocampus and cerebellum.

Code Video Cerebral Valley

Core trick

Joins cell-type H3K27ac and H3K27me3 signal to CRE-gene links and RNA expression to score pathway remodeling per cell type.

Tags

healthscience

Description

To understand how Alzheimer’s disease reshapes the brain’s regulatory landscape cell type by cell type, I used Claude Science to analyze Droplet Paired-Tag data from 10 donors across the hippocampus and cerebellum. This method measures RNA together with two histone marks in the same nucleus: H3K27ac, associated with active enhancers, and H3K27me3, associated with Polycomb repression. The analysis produced a two-mark cis-regulatory atlas and identified coordinated pathway-level remodeling in specific cell types. The main finding was a region-specific glial chromatin switch in the AD-vulnerable hippocampus. Reactive astrocytes gained H3K27ac at inflammatory programs, including NF-κB, IL-1, and IL-6 signaling, while homeostatic astrocytes lost enhancer activity. At the same time, homeostatic microglia lost H3K27me3, suggesting de-repression or priming before full activation. These results support a testable model in which AD glial reactivity is an ordered, chromatin-encoded state transition, potentially initiated by local pathology. By integrating chromatin change, CRE–gene links, RNA expression, and AD genetics, the analysis also prioritized candidate targets, led by SORL1 in hippocampal microglia, and motivated a three-aim proposal to test where the switch occurs, what drives it, and why it matters.
Xiaxhan/AD_CUTtag_claude_science★ 10 forksRCreated Jul 13, 2026 · last push Jul 13, 2026

README excerpt

# AD CUT&Tag Analysis with Claude Science

This repository contains the analysis workflow, code, selected figures, and summarized results generated for the **Built with Claude: Life Sciences Hackathon**.

Please review the summary in `output/REPORT.md`

## Project overview

This project uses single-nucleus CUT&Tag data from Alzheimer’s disease (AD) brain samples to characterize cell-type-specific epigenomic remodeling.

The analysis demonstrates how Claude Science can support biological interpretation, experimental target prioritization, integration of chromatin and gene-expression evidence, and development of a mechanistically focused research proposal.

## Repository structure

* `scripts/`: analysis and visualization code
* `output/`: selected reports, figures, and summarized results
* `Project.md`: project instructions, analysis plan, and Claude Science workflow

## Key outputs

1. **Complete analysis summary:** [`output/REPORT.md`](output/REPORT.md)  
   Documents the full analysis workflow, results, and initial biological interpretation.

2. **Critical review and target prioritization:** [`output/AD_CRE_story_summary.md`](output/AD_CRE_story_summary.md)  
   Refines the biological interpretation and prioritizes candidate genes and regulatory elements for experimental validation.

3. **Grant proposal strategy:** [`output/grant_strategy_memo.md`](output/grant_strategy_memo.md)  
   Translates the findings into a mechanistically focused research question, specific aims, ex

Team