| --- |
| 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 |
|
|
