pen-stack 7.2.1__tar.gz → 7.2.2__tar.gz

{pen_stack-7.2.1 → pen_stack-7.2.2}/CHANGELOG.md

@@ -3,6 +3,24 @@
 All notable changes to PEN-STACK are documented here. This file follows
 [Keep a Changelog](https://keepachangelog.com/).
 
+## [7.2.2] - 2026-07-02 - Integrase: precise capability framing (the negative is about a method, not the biology)
+
+A framing/presentation refinement of the v7.2.1 sealed-negative result — no science changes, the number is
+unchanged and the negative stands.
+
+### Changed
+- **Precise claim, everywhere:** what the sealed PhiC31 benchmark showed is that a specific *method* (attP
+  sequence-similarity scanning) is insufficient — **NOT** that pseudosites are unpredictable. The signal is real
+  (Chalberg's palindromic consensus; IntQuery's success on 410,776 cryptic attB), just not capturable by simple
+  identity. So the honest, narrow claim is "sequence similarity is insufficient," and this negative is the
+  empirical justification for a learned/DMS model (the indicated next step). Sharpened in `offtarget_integrase.py`,
+  `phic31_recall_metrics.json`, and the data card so nothing reads as "unpredictable."
+- **App presentation:** `nominate_integrase` now returns a `capability` disclosure (badge + plain microcopy). The
+  Off-Target page shows a badge reading **"mechanism-based · not predictive by sequence alone"** (not a bare red
+  flag) plus one line — *"φC31 pseudosite activity is sequence-guided but not predictable from similarity alone
+  (sealed benchmark, negative); confirm empirically"* — separating the grounded facts (verified att + documented
+  pseudo-attP with GenBank accessions) from the honest capability limit. A trust-building disclosure, not an alarm.
+
 ## [7.2.1] - 2026-07-02 - PhiC31 integrase: close the O-WS3/O-G2 data gap with verified data + a sealed recall benchmark (honest NEGATIVE)
 
 Closes the one genuine open item from v7.2.0 — the PhiC31 integrase data gap — with independently-verified,

{pen_stack-7.2.1 → pen_stack-7.2.2}/CITATION.cff

@@ -1,7 +1,7 @@
 cff-version: 1.2.0
 message: "If you use PEN-STACK, please cite it as below."
 title: "PEN-STACK: open infrastructure for genome writing"
-version: 7.2.1
+version: 7.2.2
 date-released: 2026-07-02
 authors:
   - family-names: "Mahaboob Ali"

{pen_stack-7.2.1 → pen_stack-7.2.2}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.2.1
+Version: 7.2.2
 Summary: Open infrastructure for genome writing: the Writable Genome atlas, the Writer Atlas, and the Write Planner.
 Author-email: Anees Ahmed Mahaboob Ali <ahmedaneesm@gmail.com>
 License: MIT

{pen_stack-7.2.1 → pen_stack-7.2.2}/benchmarks/offtarget/integrase/SHA256SUMS

@@ -1,4 +1,4 @@
 701efce23441ba6ec3865060aa3a749d7165d013628f3ed8010737861b306557  README.md
 888dd4ba69bbe1eccd323797adc89b242b1c8ec6208a5f9f41df839d641d10e6  harness.py
 fe23827ff34204bc2cd1f903fcd3e32b120c4521787342e6590824249573a4d4  phic31_pseudo.fasta
-2a0f22d700f0db0bafd1c98b8b8893f14e86ae9574ff789042bd3ad1c7f6a3c0  phic31_recall_metrics.json
+8ac9ee21ddab7ddc9af4d68f6eef872c30069f6dbc6ae8de89f62c981d1868cd  phic31_recall_metrics.json

{pen_stack-7.2.1 → pen_stack-7.2.2}/docs/cards/offtarget_data.md

@@ -103,7 +103,7 @@ disclosure** where it does not. No mechanism is ever presented as validated wher
 | Writer class | Mechanism | Enumeration | Status | Ground truth / benchmark |
 |---|---|---|---|---|
 | **Nuclease** (SpCas9/SaCas9/Cas12a) | mismatch-tolerant cleavage at protospacer+PAM | Cas-OFFinder genome scan | ✅ **validated** | 4-assay Off-Target-Bench (above) + **O-G1**: enumeration recovers 100% of EMX1's documented GUIDE-seq off-targets ≤5 mm |
-| **Serine integrase** (Bxb1, PhiC31) | recombination at genomic pseudo-attP | fixed-sequence att-window scan | 🔵 **mechanism-based, sealed-NEGATIVE benchmark** (v7.2.1) | att verified (Bxb1: FlyBase FBto0000359 / Ghosh 2003 `10.1016/S1097-2765(03)00444-1`; PhiC31: **PDB 9U2T/9U2S** + Groth 2000 `10.1073/pnas.090527097`); the PhiC31 human pseudo-attP set is verified (Thyagarajan 2001, **GenBank AF333429/30/31**, `10.1128/MCB.21.12.3926-3934.2001`; chr8/16/15). The v7.2.1 **SEALED recall benchmark** (`benchmarks/offtarget/integrase/`) is **NEGATIVE**: att-sequence-similarity does NOT recover the documented pseudo-attP above random background (all three at 14 mm / 30 bp = the background median). The genome-wide similarity RANKING is therefore **unvalidated** — φC31 recognition needs palindromic architecture (Chalberg 2006, `10.1016/j.jmb.2005.11.098`) / a learned model (IntQuery), not raw identity. Documented pseudosites surfaced as verified known loci; the negative is reported verbatim (a stronger, more honest O-G2 than an untested "semi-validated"). |
+| **Serine integrase** (Bxb1, PhiC31) | recombination at genomic pseudo-attP | fixed-sequence att-window scan | 🔵 **mechanism-based, sealed-NEGATIVE benchmark** (v7.2.1) | att verified (Bxb1: FlyBase FBto0000359 / Ghosh 2003 `10.1016/S1097-2765(03)00444-1`; PhiC31: **PDB 9U2T/9U2S** + Groth 2000 `10.1073/pnas.090527097`); the PhiC31 human pseudo-attP set is verified (Thyagarajan 2001, **GenBank AF333429/30/31**, `10.1128/MCB.21.12.3926-3934.2001`; chr8/16/15). The v7.2.1 **SEALED recall benchmark** (`benchmarks/offtarget/integrase/`) is **NEGATIVE**: att-sequence-similarity does NOT recover the documented pseudo-attP above random background (all three at 14 mm / 30 bp = the background median). The genome-wide similarity RANKING is therefore **not predictive by sequence alone**. **Precise claim:** what failed is a specific *method* (attP sequence-similarity), NOT the existence of predictable pseudosites — the signal is real (Chalberg 2006's palindromic consensus `10.1016/j.jmb.2005.11.098`; IntQuery's 410,776 cryptic attB), just not capturable by simple identity. "Sequence similarity is insufficient," never "unpredictable." This negative is the empirical justification for a learned/DMS model (the indicated next step). Documented pseudosites surfaced as verified known loci; the negative is reported verbatim (a stronger, more honest O-G2 than an untested "semi-validated"). |
 | **Bridge** (IS110/IS621) | recombination at bridge-RNA target-loop matches | core-seeded genome scan (pysam) | 🔵 **mechanism-based, unvalidated** | **NO genome-wide unbiased CELLULAR off-target assay exists** (technology ~2024). The mismatch-tolerance RANKER is validated on the measured Perry-2025 in-vitro DMS specificity (held-out ranking AUROC 0.88), but genomic recovery is unvalidated. |
 | **CAST** (ShCAST V-K / VchCAST I-F) | guide-directed integration + guide-independent untargeted transposition | spacer scan + per-system untargeted background | 🔵 **mechanism-based, unvalidated** | untargeted-transposition rates documented per system (`data/curated/cast_systems.yaml`): ShCAST high/AT-biased (Strecker 2019 `10.1126/science.aax9181`; Science 2024 `10.1126/science.adj8543`), VchCAST >95–99% on-target (Klompe 2019 `10.1038/s41586-019-1323-z`; Vo 2021 `10.1038/s41587-020-00745-y`). No genome-wide cellular assay for human-cell CAST. |
 | **PASTE / (ee)PASSIGE** | Cas9-nickase off-target + integrase pseudo-attP | compose(nuclease, integrase) | composite (✅ nickase + 🟡 integrase) | inherits the nuclease benchmark for the nickase and the integrase status for the installed att; recommends BOTH a nuclease assay AND an integrase assay |

{pen_stack-7.2.1 → pen_stack-7.2.2}/pen_stack/__init__.py

@@ -1,2 +1,2 @@
 """PEN-STACK v3.0 - open infrastructure for genome writing."""
-__version__ = "7.2.1"
+__version__ = "7.2.2"

{pen_stack-7.2.1 → pen_stack-7.2.2}/pen_stack/wgenome/offtarget_integrase.py

@@ -24,6 +24,22 @@ _ALIAS = {"bxb1": "Bxb1", "serine_integrase": "Bxb1", "pe_integrase": "Bxb1",
           "phic31": "PhiC31", "phic31_integrase": "PhiC31"}
 _CONFIRM = "Cryptic-seq / HIDE-seq (Tome Biosciences, 2024 preprint)"
 
+# Capability disclosure (v7.2.2): be PRECISE about what the sealed benchmark showed. What failed is a specific
+# METHOD (attP sequence-similarity scanning), NOT the existence of predictable pseudosites — the signal is real
+# (Chalberg's ~30-bp palindromic consensus; IntQuery's success on 410,776 cryptic attB), just not capturable by
+# simple similarity. The honest claim is narrow: "sequence similarity is insufficient", never "unpredictable".
+_CAPABILITY = {
+    "badge": "mechanism-based · not predictive by sequence alone",
+    "microcopy": ("phiC31 pseudosite activity is sequence-guided but NOT predictable from similarity alone "
+                  "(sealed benchmark, negative); confirm empirically (Cryptic-seq / HIDE-seq)."),
+    "what_failed": ("attP sequence-SIMILARITY scanning (a specific method) — NOT the existence of predictable "
+                    "pseudosites."),
+    "signal_is_real": ("the pseudosite signal IS real — Chalberg's ~30-bp palindromic consensus and IntQuery's "
+                       "success on 410,776 cryptic attB show it — just not capturable by simple sequence identity."),
+    "indicated_next_step": ("a learned / DMS model (as IntQuery uses); this sealed negative is the empirical "
+                            "justification for it, not evidence that pseudosites are unpredictable."),
+}
+
 
 @lru_cache(maxsize=1)
 def integrase_att() -> dict:
@@ -69,15 +85,17 @@ def nominate_integrase(integrase: str = "Bxb1", top: int = 20) -> dict:
                 "att_doi": rec["doi"], "pdb": rec.get("pdb"),
                 "documented_pseudo_attP": rec.get("pseudo_attP_positive_set"),
                 "documented_source": rec.get("positive_set_source"), "documented_doi": rec.get("positive_set_doi"),
-                "sealed_recall_benchmark": bench, "similarity_ranking_validated": False,
+                "sealed_recall_benchmark": bench, "similarity_ranking_validated": False, "capability": _CAPABILITY,
                 "specificity_note": rec.get("specificity_note"),
                 "method": ("PhiC31 documented human pseudo-attP (verified GenBank AF333429/30/31, Thyagarajan 2001) "
-                           "are surfaced as known off-target loci; the att-similarity genome scan is mechanism-"
-                           "based and its SEALED recall benchmark is NEGATIVE (does not recover them above "
-                           "background) -> the genome-wide ranking is unvalidated (reported verbatim)."),
+                           "are surfaced as verified known off-target loci. Separately, the att-SIMILARITY genome "
+                           "scan is a mechanism-based method whose sealed recall benchmark is NEGATIVE: sequence "
+                           "similarity is INSUFFICIENT to rank these sites (the signal is real but needs a learned "
+                           "model, not raw identity). Reported verbatim."),
                 "confirm_assay": _CONFIRM,
-                "honesty": "verified documented pseudosites + an honest NEGATIVE recall benchmark; NOT a validated "
-                           "predictor and NOT a clearance.",
+                "honesty": "verified documented pseudosites (grounded facts) PLUS an explicit capability disclosure: "
+                           "sequence-similarity scanning does not reliably rank them; NOT a clearance. Confirm "
+                           "empirically.",
                 "nomination_is_not_clearance": True}
 
     # Bxb1 (and any integrase with a committed genome-scan cache): genome-wide similarity candidates
@@ -100,12 +118,12 @@ def nominate_integrase(integrase: str = "Bxb1", top: int = 20) -> dict:
             "scan_window": window, "source": enum["source"], "att_doi": rec["doi"],
             "n_sites_genome_wide": len(noms), "nominations": noms[:top],
             "specificity_note": rec.get("specificity_note"),
-            "sealed_recall_benchmark": bench, "similarity_ranking_validated": False,
+            "sealed_recall_benchmark": bench, "similarity_ranking_validated": False, "capability": _CAPABILITY,
             "method": ("fixed-sequence Cas-OFFinder scan of the attP core window over GRCh38, scored by att-arm "
-                       "similarity. The similarity RANKING is mechanism-based and UNVALIDATED: the sealed PhiC31 "
-                       "recall benchmark is NEGATIVE (att-similarity does not recover documented pseudo-attP "
-                       "above background)."),
+                       "similarity. The similarity RANKING is mechanism-based and NOT predictive by sequence alone: "
+                       "the sealed PhiC31 recall benchmark is NEGATIVE (sequence similarity is insufficient to "
+                       "rank pseudo-attP; the signal is real but needs a learned model, per IntQuery)."),
             "confirm_assay": _CONFIRM,
-            "honesty": "genome-wide pseudo-attP candidates by att similarity; the ranking is unvalidated "
-                       "(sealed-negative benchmark) and NOT a clearance.",
+            "honesty": "genome-wide pseudo-attP candidates by att similarity; sequence similarity is insufficient "
+                       "to rank them (sealed-negative benchmark) -> mechanism-based, confirm empirically. NOT a clearance.",
             "nomination_is_not_clearance": True}

{pen_stack-7.2.1 → pen_stack-7.2.2}/pen_stack.egg-info/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.2.1
+Version: 7.2.2
 Summary: Open infrastructure for genome writing: the Writable Genome atlas, the Writer Atlas, and the Write Planner.
 Author-email: Anees Ahmed Mahaboob Ali <ahmedaneesm@gmail.com>
 License: MIT

{pen_stack-7.2.1 → pen_stack-7.2.2}/pyproject.toml

@@ -4,7 +4,7 @@ build-backend = "setuptools.build_meta"
 
 [project]
 name = "pen-stack"
-version = "7.2.1"
+version = "7.2.2"
 description = "Open infrastructure for genome writing: the Writable Genome atlas, the Writer Atlas, and the Write Planner."
 readme = "README.md"
 requires-python = ">=3.11"