@platforma-open/milaboratories.generation-probability.block 1.0.0
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- package/block-pack/CHANGELOG.md +14 -0
- package/block-pack/block-logo.png +0 -0
- package/block-pack/description.md +13 -0
- package/block-pack/main.plj.gz +0 -0
- package/block-pack/manifest.json +1 -0
- package/block-pack/model.json +1 -0
- package/block-pack/organization-logo.png +0 -0
- package/block-pack/published.json +8 -0
- package/block-pack/ui.tgz +0 -0
- package/dist/AGENTS.d.ts +12723 -0
- package/dist/AGENTS.d.ts.map +1 -0
- package/dist/AGENTS.js +0 -0
- package/dist/index.d.ts +12736 -0
- package/dist/index.d.ts.map +1 -0
- package/dist/index.js +12652 -0
- package/dist/index.js.map +1 -0
- package/package.json +63 -0
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# @platforma-open/milaboratories.generation-probability.block
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## 1.0.0
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### Major Changes
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- 1026dfe: Initial release.
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- Per-clonotype generation probability (Pgen) via OLGA on BCR and TCR
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repertoires from MiXCR clonotyping.
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- Human and mouse models for IGH, IGK, IGL, TRA, and TRB; recombination
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model resolved from dataset species and per-chain locus metadata.
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- Emits raw Pgen and -log10(Pgen) per chain (heavy/light for BCR,
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beta/alpha for TCR).
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# Overview
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For every clonotype in a repertoire, this block computes the chance that V(D)J recombination would build its exact CDR3 by chance, before any immune selection — a value called its generation probability (Pgen). Some CDR3s form readily through many recombination paths (high Pgen); others sit far from the sequences recombination favors and are rare (low Pgen). Pgen spans about twenty orders of magnitude across a repertoire, so it ranks clonotypes on a scale that V/J gene usage and clone abundance cannot.
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What a rare CDR3 means depends on your data. In post-immunisation antibody (BCR) repertoires, a rare heavy-chain CDR3 has drifted far from germline through affinity maturation, so Pgen ranks lead candidates by that distance. T-cell (TCR) repertoires undergo no somatic hypermutation, so there Pgen instead separates common public CDR3s — shared across people by chance — from rare, clonally expanded ones.
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Each clonotype carries the raw Pgen and its −log10 form, where a higher −log10 marks a rarer CDR3, computed on its primary chain. These values feed downstream ranking blocks such as Lead Selection.
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# Method
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Pgen is computed with [OLGA](https://github.com/statbiophys/OLGA) v1.3.0, which sums over the V(D)J recombination paths that yield each CDR3 under a learned model. Calibrated models cover human and mouse across IGH / IGK / IGL / TRA / TRB. On anything else — another species such as camelid, or sequences with no true V(D)J origin such as display libraries and synthetic sets — OLGA still returns a number, but one with no biological meaning. OLGA is distributed under GPL-3.0.
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> Sethna Z, Elhanati Y, Callan CG Jr, Walczak AM, Mora T. OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs. _Bioinformatics_ 35(17):2974–2981, 2019. [doi:10.1093/bioinformatics/btz035](https://doi.org/10.1093/bioinformatics/btz035)
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