CRISPRme v2.3.0

The dict-less variant-analysis engine: replaces the ~152 GB per-sample SNP
dictionaries with compact, memory-mapped tiers, adds population-level off-target
summaries, and corrects the allele-frequency column. Backward-compatible — a
dict-based install still works unchanged.

Added

• Compact dict-less variant post-analysis. A tiny, always-shipped Tier-0
  registry (per-(pos,alt) AC/AN + per-(db×subpop)/global allele counts + rsID,
  mmap+bisect) powers off-target detection and corrected allele frequencies out of
  the box; an optional Tier-1 genotype store reconstructs the exact per-sample
  Samples column. Together they replace the 152 GB per-sample dicts with ~7 GB
  (registry) + ~22 GB (genotype tier), random-access — SNP post-analysis no longer
  streams 152 GB of per-sample JSON. build-index-only emits the tiers; the search
  auto-detects and uses them (falling back to dicts when present).
• Combination-aware population-summary output — a <output>.population_summary.tsv
  companion per variant off-target with per-database, per-superpopulation and global
  allele/carrier frequencies, max-subpopulation AF (+label), homozygote counts and
  absolute Ns, with dataset provenance preserved (never conflates 1000G vs HGDP).
  Phased datasets use exact cis co-occurrence; unphased report an assume-cis upper
  bound + a labeled lower bound.
• Dict-less HuggingFace distribution. publish-index --dictless ships the
  registry in the main index tarball + the genotype tier as a separate optional
  genotypes_<vcf>.tar.gz; download fetches the genotype tier by default
  (--no-genotypes to skip). Published NRG_3_hg38-dictless+hg38_1000G_HGDP on
  lucapinello/crisprme-data (the dict-based NRG_3/NGG_3 indexes remain the
  default). Fetch it with download --what all first, then download --what index,
  so the per-dataset samplesID lists are on disk when the combined
  <vcf>.samplesID.txt is auto-synthesized (a standalone --what index without a
  prior samples fetch leaves the combined file absent — hardening tracked as a
  follow-up).

Fixed

• Corrected allele frequencies. The AF column — empty/mis-polarized for ~95 % of
  variants in the dict format (a documented 2.2.0 limitation) — is re-derived from
  AC/AN over the full panel.
• Out-of-the-box dict-less install. The skip-enrichment gates
  (submit_job_automated_new_multiple_vcfs.sh, validate_inputs.py) now accept a
  registry_<vcf>/ tier in place of dictionaries_<vcf>/; download installs a
  -dictless-named index under its search-resolvable canonical name and synthesizes
  the combined <vcf>.samplesID.txt from the per-db files. Verified end-to-end: a
  fresh dict-less download finds the CPS1 off-target (chr2:210530658, CFD 0.947,
  rs114518452) with Samples reconstructed from the genotype tier and a populated
  population summary.