v2.4.0: squash history to reclaim LFS storage after trimming raw VCFs + legacy files (current tree unchanged)

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README.md

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+---
+license: agpl-3.0
+pretty_name: CRISPRme reference data & precomputed indexes
+tags:
+  - crispr
+  - off-target
+  - genomics
+  - crisprme
+  - reference-data
+viewer: false
+---
+
+# CRISPRme reference data & precomputed indexes
+
+A fast, reliable mirror of the reference resources CRISPRme needs, plus
+**precomputed indexes** for the default references — so users can skip the slow
+raw-data download, the multi-hour variant **enrichment**, and the index build
+entirely.
+
+> **Status:** 🚧 work in progress — this repository is being populated. Layout and
+> filenames below are the target structure; not all assets are uploaded yet.
+
+## Why this exists
+
+A genuine from-scratch, genome-wide CRISPRme run was measured end-to-end and the
+cost is almost entirely **data movement + enrichment**, not the search:
+
+- Downloading the 1000 Genomes VCFs from EBI ran at **~1.4 MB/s (~3 h)**; the
+  UCSC genome download is similarly throttled. **Hugging Face measured ~6.5×
+  faster** from the same machine.
+- The variant **enrichment** stage was **~93 % of the ~13.5 h wall-clock**
+  (single-threaded per chromosome).
+
+Hosting the data here (fast CDN) and — more importantly — shipping **precomputed
+indexes** removes the download **and** the enrichment/index-build for the common
+case, taking a genome-wide setup from many hours to minutes.
+
+## Target layout
+
+```
+crisprme-data/
+├── genomes/
+│   └── hg38/                      # per-chromosome FASTA (chr1.fa … chrX.fa)
+├── vcfs/
+│   ├── 1000G/                     # 1000 Genomes Phase 3 (GRCh38)
+│   ├── HGDP/                      # Human Genome Diversity Project
+│   └── unions/                    # combined cohorts (see "Default references")
+├── annotations/                  # dhs+encode+gencode.hg38.bed, gencode.protein_coding.bed
+├── pams/                          # e.g. 20bp-NGG-spCas9.txt, NNN motifs
+├── samplesIDs/                    # per-dataset sample id lists
+└── indexes/                       # PRECOMPUTED genome_library + enriched indexes
+    ├── NGG_1000G+HGDP+TOPMed+AllofUs/
+    ├── NNN_1000G+HGDP/            # backward-compatible with the original CRISPRme
+    └── NGG_pangenome2.0/
+```
+
+## Default references (shipped as precomputed indexes)
+
+Two headline references (highlighted in the manuscript):
+
+1. **Unified large-cohort panel** — 1000G + HGDP + TOPMed + All of Us.
+2. **Pangenome 2.0** VCF.
+
+Plus an **NNN + 1000G+HGDP** configuration for backward compatibility with the
+original CRISPRme, and default PAMs **NNN** and **NGG**.
+
+## Usage
+
+CRISPRme's `setup` will be able to pull these resources from this repository
+instead of the original (slow) upstream hosts. Direct download also works, e.g.:
+
+```bash
+# whole repo (large) — prefer fetching only what you need
+hf download pinellolab/crisprme-data --repo-type dataset --local-dir crisprme-data
+```
+
+## License & citation
+
+Reference data are redistributed under the terms of their original sources
+(1000 Genomes, HGDP, GENCODE/ENCODE, UCSC hg38, etc.). CRISPRme is AGPL-3.0.
+
+If you use CRISPRme, please cite:
+Cancellieri S, *et al.* Human genetic diversity alters off-target outcomes of
+therapeutic gene editing. *Nat Genet* 55, 34–43 (2023).
+doi:10.1038/s41588-022-01257-y
+
+Project: https://github.com/pinellolab/CRISPRme

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