Work

Evolutionarily conserved coupling of lysosomal response sensing and disease-associated microglial reprogramming scales with pathological timescales

Year: 2026
Type: article
Abstract: This Zenodo record contains the analysis code and the source data for the manuscript: "Evolutionarily conserved coupling of lysosomal response sensing and disease-associated microglial reprogramming scales with pathological timescales" Data re-analysed (all public; no new data were generated in this study): Murine: GSE90975 (facial nerve axotomy; 10 animals, 1,437 cells), GSE121654 (corpus callosum LPC demyelination; 6 animals, 5,325 cells) and GSE98969 (5xFAD, Trem2-KO and Trem2-KO × 5xFAD; brain, 28 C57BL/6 and 31 5xFAD plates retained under a ≥20-cells-per-plate rule). Human: Lee 2026 (578 donors), Rexach 2024 (38 donors) and SEA-AD (84 donors), obtained from CZ CELLxGENE and the Allen Institute. Multiple sclerosis white matter: GSE118257 (5 donors; lesion-type boundary analysis, Supplementary Fig. S16). AD GWAS summary statistics: Bellenguez et al. 2022 (GCST90027158), analysed with MAGMA v1.10. Code (152 files, 11 modules): 00_setup restores local data paths; 01_preprocessing (QC, Harmony, Leiden, C1 identification); 02_main_analysis (cluster-robust OLS, mixed-effects models, Fisher z pooling, three-level decomposition, leave-one-out); 03_sensitivity (Harmony parameter scan, meta-analysis, E-values, negative controls, dose–response); 04_tables; 05_figures (Fig. 1–7 and Table 1, final panel order); 06_supplementary_figures (S1–S16); 07_audit; 08_supp_projections (C1-like projection and shared-gene removal, Supplementary Figs. S9–S10); 09_source_data and 10_assemble (workbook assembly). All inference is performed at the animal, sequencing-plate or donor level. Source data: Source_Data_2026-11-06_FINAL_v2.xlsx, 109 worksheets covering every main-figure panel, Supplementary Tables S1–S21 and the S1–S16 figure data; SHEET_MAP.md maps each worksheet to its generating script, and MANIFEST.csv records provenance and checksums. Environment: Python ≥3.12 with scanpy 1.12.3, anndata 0.13.2, numpy 2.4, scipy 1.18 and statsmodels 0.14 (requirements.txt, environment.yml). Absolute file paths are not distributed: scripts contain the placeholder __DATA_ROOT__, restored with python code/00_setup/set_data_root.py "path/to/data". DOI: 10.5281/zenodo.23259475 Code also available at: https://github.com/lzo220/Yunlong-Liang License: MIT for the code; the source data remain subject to the terms of the original repositories.
Language: English
Subfield: Neurology
Open Access status: green
OpenAlex ID: W7225430651
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