pen-stack 7.1.3__tar.gz → 7.1.4__tar.gz

{pen_stack-7.1.3 → pen_stack-7.1.4}/CHANGELOG.md

@@ -3,6 +3,31 @@
 All notable changes to PEN-STACK are documented here. This file follows
 [Keep a Changelog](https://keepachangelog.com/).
 
+## [7.1.4] - 2026-06-29 - Germline-prohibition legality rule
+
+### Added
+- **Compliance rule category + `compliance.germline_prohibition` (hard_reject).** A heritable / germline edit
+  previously passed the Legality axis because no rule existed for it (the only germline handling was a
+  known-unknown scope matcher for *questions*, not *designs*). The new rule fails legality for: a reproductive
+  germline target cell (embryo / zygote / oocyte / sperm / gamete - unconditional), a declared reproductive-use
+  intent (gametes / assisted reproduction / implantation / "for reproduction"), a declared heritable intent
+  (germline / heritable / "transmitted to offspring"), or a germline-competent cell type (hESC / iPSC) edited in a
+  heritable context (in vivo, or a reproductive/heritable intent). It is cited (Lander et al. 2019 moratorium,
+  `10.1038/d41586-019-00726-5`; US National Academies 2017, `10.17226/24623`) and emits a proof-object repair hint
+  (restrict to somatic / ex-vivo editing). It is a scope-of-use legality bound, reported on the LEGALITY axis,
+  separate from the Biosecurity axis. The category is wired into every write type; `rule_spec.json` is now 11 rules.
+- **Paraphrase + negation robustness** (red-team-hardened). The free-text intent match is NEGATION-aware
+  (negated-span detection), so a somatic design that explicitly says "somatic, not germline" / "no germline
+  transmission" / "NOT for reproduction or implantation" is not false-flagged, while paraphrased reproductive
+  intent (e.g. "generate gametes for assisted reproduction", "embryo intended for uterine transfer") with no
+  literal "germline"/"heritable" word still fails. Validated against a 30-design adversarial set: 0 evasions,
+  0 false positives.
+
+### Fixed
+- The Verify page's Legality description claimed it adjudicates "jurisdiction / list-agent / IP", which it does
+  not. Corrected to describe the actual legality axis (physical feasibility + germline scope-of-use compliance),
+  noting that dual-use hazard is the separate Biosecurity axis.
+
 ## [7.1.3] - 2026-06-26 - Designer correctness: Guardian biosecurity + calibrated confidence
 
 ### Fixed

{pen_stack-7.1.3 → pen_stack-7.1.4}/CITATION.cff

@@ -1,8 +1,8 @@
 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: 7.1.3
-date-released: 2026-06-26
+version: 7.1.4
+date-released: 2026-06-29
 authors:
   - family-names: "Mahaboob Ali"
     given-names: "Anees Ahmed"

{pen_stack-7.1.3 → pen_stack-7.1.4}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.1.3
+Version: 7.1.4
 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-7.1.4/configs/rules/compliance.yaml

@@ -0,0 +1,44 @@
+# Compliance / scope-of-use legality (v7.1.4). PEN-STACK is a SOMATIC genome-writing design tool: it does not
+# model germline transmission, embryonic development, or heritable outcomes, and it does not support designing a
+# heritable human germline edit. A design that declares a heritable / germline-editing intent, OR that targets a
+# reproductive germline cell, OR that edits a germline-competent cell type in vivo, is a HARD legality reject -
+# heritable human germline genome editing is broadly prohibited / under international moratorium (it is NOT a
+# biosecurity-hazard signature, so it must fail on the LEGALITY axis, leaving biosecurity to its own screen).
+category: compliance
+rules:
+  - id: compliance.germline_prohibition
+    kind: hard_reject
+    category: compliance
+    mechanism: "heritable human germline editing is out of scope for this somatic tool and broadly prohibited: a declared germline/heritable intent, a reproductive germline target cell, or an in-vivo edit of a germline-competent cell type is rejected"
+    evaluator: germline_prohibition
+    param:
+      # reproductive germline cells: editing these IS germline (always reject, any context; matched on the
+      # structured cell_type field, so no negation handling needed).
+      germline_cell_types: ["embryo", "zygote", "oocyte", "ovum", "egg cell", "sperm", "spermatozoa",
+                            "spermatocyte", "spermatogonia", "spermatogonial", "gamete", "germ cell", "germline",
+                            "primordial germ", "pgc", "blastocyst", "conceptus", "morula", "preimplantation"]
+      # germline-competent pluripotent cells: editing these in a HERITABLE context (in vivo, or a reproductive /
+      # heritable intent) is a germ-lineage edit; an ex-vivo SOMATIC use of the same research line is in scope.
+      germline_competent_cell_types: ["h1_hesc", "hesc", "embryonic stem", "ipsc", "ips cell", "ipscs",
+                                      "pluripotent stem", "epiblast", "inner cell mass"]
+      # STRONG reproductive-use intent: describes a reproductive PURPOSE; matched negation-aware in the free text.
+      reproductive_intent_terms: ["gamete", "gametes", "generate gametes", "derive gametes", "primordial germ",
+                                  "germ lineage", "germ-line", "germ line", "for reproduction", "reproductive use",
+                                  "reproductive purpose", "assisted reproduction", "ivf", "in vitro fertilization",
+                                  "implantation", "uterine transfer", "fertilized egg", "for pregnancy",
+                                  "destined for transfer", "slated for transfer", "scheduled for implantation",
+                                  "intended for pregnancy", "reproductive editing"]
+      # WEAKER heritable-transmission intent: can also appear inside a negated somatic disclaimer, so matched
+      # negation-aware (a design that says "not heritable" / "no germline transmission" does not fire on these).
+      heritable_terms: ["germline", "heritable", "inheritable", "inherited by", "inherit the", "heritably",
+                        "pass to offspring", "passed to offspring", "passed down to", "transmit to offspring",
+                        "transmit the fix to", "transmissible to progeny", "transmitted to the", "to progeny",
+                        "to descendants", "to the patient's children", "to the man's offspring",
+                        "future generations", "future generation", "next generation edit", "germ cell editing",
+                        "embryo editing", "embryonic editing", "carried by the resulting child",
+                        "inheritable by future"]
+    provenance:
+      doi: ["10.1038/d41586-019-00726-5", "10.17226/24623"]
+      note: "Heritable human germline genome editing is broadly prohibited / under moratorium: Lander et al. 2019 international call for a moratorium (Nature 567:165); US National Academies 2017 'Human Genome Editing: Science, Ethics, and Governance'; WHO Expert Advisory Committee framework (2021); US FDA is barred from considering heritable-germline clinical applications (Consolidated Appropriations Act rider); Council of Europe Oviedo Convention Art. 13. PEN-STACK is a SOMATIC tool and takes no position on germline editing beyond declaring it out of scope."
+    test_ref: "tests/unit/test_ws_r.py::test_germline_edit_fails_legality"
+    scope: "a scope-of-use / regulatory legality bound, not a biosecurity-hazard signature and not an efficacy claim"

{pen_stack-7.1.3 → pen_stack-7.1.4}/configs/write_types.yaml

@@ -9,35 +9,35 @@ write_types:
   insertion:
     status: supported
     description: "insert a cargo at a safe/durable locus"
-    rule_categories: [reachability, fold, payload, delivery]
+    rule_categories: [reachability, fold, payload, delivery, compliance]
     steps: [site_selection, writer_selection, cargo_design, offtarget, structural_risk, verify]
     writer_classes: [bridge, cast, serine_integrase, pe_integrase]
 
   excision:
     status: coverage_only
     description: "excise a segment (e.g. BCL11A enhancer, FXN GAA repeat) via a recombinase/nuclease pair"
-    rule_categories: [reachability, multiplex, delivery]
+    rule_categories: [reachability, multiplex, delivery, compliance]
     steps: [breakpoint_reachability, pair_safety, delivery, verify]
     writer_classes: [serine_integrase, recombinase, nuclease_pair]
 
   inversion:
     status: coverage_only
     description: "invert a segment between two recombination sites"
-    rule_categories: [reachability, multiplex, delivery]
+    rule_categories: [reachability, multiplex, delivery, compliance]
     steps: [site_pair_reachability, orientation_check, delivery, verify]
     writer_classes: [serine_integrase, recombinase]
 
   replacement:
     status: coverage_only
     description: "replace a segment (excise + insert)"
-    rule_categories: [reachability, fold, payload, multiplex, delivery]
+    rule_categories: [reachability, fold, payload, multiplex, delivery, compliance]
     steps: [excision_reachability, insertion_reachability, payload, delivery, verify]
     writer_classes: [pe_integrase, serine_integrase, cast]
 
   regulatory_rewrite:
     status: coverage_only
     description: "edit a regulatory element (enhancer/silencer); routes to AlphaGenome variant-effect + scope"
-    rule_categories: [reachability, delivery]
+    rule_categories: [reachability, delivery, compliance]
     steps: [variant_effect_oracle, regulatory_scope, delivery, verify]
     writer_classes: [base_editor, pe, nuclease]
     scope_note: "regulatory-element function change is partly out of scope (structure->phenotype); flagged"
@@ -45,13 +45,13 @@ write_types:
   landing_pad_install:
     status: coverage_only
     description: "install an att landing pad (PE), then a deterministic integrase step"
-    rule_categories: [reachability, payload, delivery]
+    rule_categories: [reachability, payload, delivery, compliance]
     steps: [pe_installability, integrase_step, payload, delivery, verify]
     writer_classes: [pe_integrase]
 
   multiplex:
     status: supported
     description: "multiple concurrent edits; routes to the translocation screen"
-    rule_categories: [reachability, multiplex, delivery]
+    rule_categories: [reachability, multiplex, delivery, compliance]
     steps: [per_edit_reachability, translocation_screen, delivery, verify]
     writer_classes: [any]

{pen_stack-7.1.3 → pen_stack-7.1.4}/docs/rule_spec.md

@@ -1,6 +1,6 @@
 # Genome-writing rule spec
 
-Version 1.0. 10 rules across 5 categories (delivery, fold, multiplex, payload, reachability). A rule is data, not code: each record names the evaluator that executes it against a Design, so the rules are enumerable, queryable, and citation-backed without changing any decision (proven by the parity tests).
+Version 1.0. 11 rules across 6 categories (compliance, delivery, fold, multiplex, payload, reachability). A rule is data, not code: each record names the evaluator that executes it against a Design, so the rules are enumerable, queryable, and citation-backed without changing any decision (proven by the parity tests).
 
 Generated from `pen_stack/rules/spec.py::export_spec`. Machine-readable form: `benchmarks/verify/rule_spec.json`.
 
@@ -16,3 +16,4 @@ Generated from `pen_stack/rules/spec.py::export_spec`. Machine-readable form: `b
 | `delivery.sequence_constraints` | soft_penalty | vehicle-specific construct hazards (lentiviral internal poly(A), AAV inverted-repeat/homopolymer, recombinogenic direct repeats, GC extremes) lower titre/yield | 10.1128/JVI.79.15.9933-9944.2005 | labeled heuristic, directional; not a titre predictor |
 | `delivery.aav_packaging_margin` | soft_penalty | AAV packaging efficiency / titre drops sharply as the cargo approaches the capsid limit (computable from cargo_bp vs vehicle capacity), even while still under capacity (v4.0 delivery-oracle refinement) | 10.1089/hum.2010.245 | computable efficiency margin, directional; not a titre predictor |
 | `delivery.immunogenicity_magnitude` | scope_flag | the MAGNITUDE of immunogenicity and the precise in-vivo tropism of a vehicle are not modeled | known-unknown; surfaced, never predicted (Invariant 2) | declared out of scope; never a hard reject dressed as physics |
+| `compliance.germline_prohibition` | hard_reject | heritable human germline editing is out of scope for this somatic tool and broadly prohibited: a declared germline/heritable intent, a reproductive germline target cell, or an in-vivo edit of a germline-competent cell type is rejected (somatic/ex-vivo use of a germline-competent research line is in scope) | 10.1038/d41586-019-00726-5, 10.17226/24623 | a scope-of-use / regulatory legality bound, not a biosecurity-hazard signature and not an efficacy claim |

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack/__init__.py

@@ -1,2 +1,2 @@
 """PEN-STACK v3.0 - open infrastructure for genome writing."""
-__version__ = "7.1.3"
+__version__ = "7.1.4"

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack/rules/evaluators.py

@@ -11,6 +11,7 @@ YAML record + (if new) one evaluator here, never scattered ``if`` checks in the
 """
 from __future__ import annotations
 
+import re
 from collections.abc import Callable
 
 from pen_stack.rules.schema import Design, Rule, RuleResult
@@ -204,6 +205,95 @@ def delivery_immunogenicity_scope(design: Design, rule: Rule) -> RuleResult:
                    "(declared out of scope, never predicted)")
 
 
+# --------------------------------------------------------------------------------------------------
+# compliance / scope-of-use legality (v7.1.4): heritable human germline editing is out of scope + prohibited
+# --------------------------------------------------------------------------------------------------
+# A term in declared free text counts only if it is NOT inside a NEGATED span, so a somatic design that says
+# "no germline transmission", "not heritable", "somatic, not germline", or "NOT for reproduction or implantation"
+# (a distributed negation over a list) does not false-fire on the negated word. A negator opens a span that runs
+# across list connectors (or / and / ,) until a clause break (. ; but however yet) or ~60 chars.
+_NEGATOR = re.compile(r"\b(not|non|no|never|without|isn'?t|aren'?t|rather than|as opposed to)\b")
+_CLAUSE_BREAK = re.compile(r"[;.]|\bbut\b|\bhowever\b|\byet\b|\bexcept\b")
+
+
+def _negated_spans(text: str) -> list[tuple[int, int]]:
+    spans = []
+    for m in _NEGATOR.finditer(text):
+        rest = text[m.end():m.end() + 60]
+        brk = _CLAUSE_BREAK.search(rest)
+        spans.append((m.start(), m.end() + (brk.start() if brk else len(rest))))
+    return spans
+
+
+def _intent_present(term: str, text: str, spans: list[tuple[int, int]]) -> bool:
+    t = str(term or "").strip().lower()
+    if not t:
+        return False
+    idx = text.find(t)
+    while idx != -1:
+        if not any(s <= idx < e for s, e in spans):
+            return True  # a non-negated occurrence
+        idx = text.find(t, idx + 1)
+    return False
+
+
+@evaluator("germline_prohibition")
+def germline_prohibition(design: Design, rule: Rule) -> RuleResult:
+    """Hard legality reject for a heritable / germline edit. Fires on (a) a reproductive germline TARGET cell
+    (embryo/zygote/oocyte/sperm/gamete - structured, unconditional), (b) a declared REPRODUCTIVE-USE intent
+    (gametes / assisted reproduction / implantation / 'for reproduction'), (c) a declared HERITABLE intent
+    (germline / heritable / transmitted to offspring), or (d) a germline-COMPETENT cell type (hESC/iPSC) in a
+    heritable context (in vivo, or a reproductive/heritable intent). The free-text intent matches are NEGATION-
+    aware, so a SOMATIC design that explicitly says 'somatic, not germline' / 'no germline transmission' / 'not
+    heritable' is NOT false-flagged, and an ex-vivo somatic use of a germline-competent research line stays in
+    scope. The screen reads the declared design artifact only (not any free-text justification)."""
+    extra = design.model_extra or {}
+
+    def _norm(x) -> str:
+        return str(x or "").strip().lower()
+
+    text = " ".join(_norm(x) for x in (design.edit_intent, extra.get("cargo_function"),
+                                       extra.get("goal_function"), extra.get("function_annotation"),
+                                       extra.get("notes")) if x)
+    ct = _norm(design.cell_type)
+    in_vivo = bool(extra.get("in_vivo")) and _norm(extra.get("in_vivo")) not in ("false", "0", "no")
+    p = rule.param
+
+    spans = _negated_spans(text)
+    repro_ct = [c for c in p.get("germline_cell_types", []) if _norm(c) in ct]
+    competent_ct = [c for c in p.get("germline_competent_cell_types", []) if _norm(c) in ct]
+    repro_intent = [t for t in p.get("reproductive_intent_terms", []) if _intent_present(_norm(t), text, spans)]
+    heritable = [t for t in p.get("heritable_terms", []) if _intent_present(_norm(t), text, spans)]
+
+    triggers = []
+    if repro_ct:
+        triggers.append(f"a reproductive germline target cell ('{repro_ct[0]}')")
+    if repro_intent:
+        triggers.append(f"a declared reproductive-use intent ('{repro_intent[0]}')")
+    if heritable:
+        triggers.append(f"a declared heritable/germline-editing intent ('{heritable[0]}')")
+    if competent_ct and (in_vivo or repro_intent or heritable):
+        ctx = "in vivo" if in_vivo else (repro_intent or heritable)[0]
+        triggers.append(f"a germline-competent cell type ('{competent_ct[0]}') edited in a heritable context "
+                        f"('{ctx}')")
+    if triggers:
+        # de-duplicate while preserving order, then report
+        seen, uniq = set(), []
+        for t in triggers:
+            if t not in seen:
+                seen.add(t)
+                uniq.append(t)
+        return _result(rule, "violate",
+                       "heritable human germline editing is out of scope for this somatic tool and is broadly "
+                       "prohibited (international moratorium): " + "; ".join(uniq)
+                       + ". Restrict to somatic editing (ex vivo, or a somatic cell type / somatic context).")
+    note = ""
+    if competent_ct:
+        note = (f" (cell type '{competent_ct[0]}' is germline-competent; somatic/ex-vivo editing of it is in "
+                "scope, but an in-vivo or reproductive heritable edit would not be)")
+    return _result(rule, "pass", "no heritable/germline-editing intent or germline target declared" + note)
+
+
 # --------------------------------------------------------------------------------------------------
 # multiplex translocation (delegates to planner.multiplex, soft penalty)
 # --------------------------------------------------------------------------------------------------

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack/rules/loader.py

@@ -10,7 +10,7 @@ from pen_stack._resources import resource
 from pen_stack.rules.schema import Rule, Ruleset
 
 RULES_VERSION = "1.0"
-_CATEGORIES = ("reachability", "fold", "payload", "multiplex", "delivery")
+_CATEGORIES = ("reachability", "fold", "payload", "multiplex", "delivery", "compliance")
 
 
 @lru_cache(maxsize=1)

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack/rules/schema.py

@@ -18,7 +18,7 @@ from pydantic import BaseModel, Field
 
 RuleKind = Literal["hard_reject", "soft_penalty", "scope_flag"]
 RuleStatus = Literal["pass", "violate", "flag", "scope", "not_applicable"]
-RuleCategory = Literal["reachability", "fold", "payload", "multiplex", "delivery"]
+RuleCategory = Literal["reachability", "fold", "payload", "multiplex", "delivery", "compliance"]
 
 
 class Rule(BaseModel):

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack/verify/proof.py

@@ -88,6 +88,13 @@ def _repair_for_violation(d: Design, rule_id: str) -> dict[str, Any] | None:
         return {"text": "the writer cannot reach the target as specified; declare a pre-installed landing pad "
                         "(installed_att) or choose a writer family whose target element is present.",
                 "repair": {"field": "installed_att", "set_to": True}}
+    if rule_id == "compliance.germline_prohibition":
+        return {"text": "this is a heritable / germline edit, which is out of scope for this somatic-editing "
+                        "tool and is broadly prohibited (international moratorium); restrict to SOMATIC editing - "
+                        "move to ex vivo (in_vivo = false) and/or a somatic cell type (e.g. hepatocytes / HepG2, "
+                        "HSPCs), and drop any germline/heritable intent. (Not auto-repairable: a germline edit is "
+                        "a change of intent, not a field fix.)",
+                "repair": None}
     return None
 
 

{pen_stack-7.1.3 → pen_stack-7.1.4}/pen_stack.egg-info/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.1.3
+Version: 7.1.4
 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-7.1.3 → pen_stack-7.1.4}/pen_stack.egg-info/SOURCES.txt

@@ -63,6 +63,7 @@ configs/expression/promoters.yaml
 configs/oracles/execution.yaml
 configs/oracles/reliability.yaml
 configs/oracles/scope_cards.yaml
+configs/rules/compliance.yaml
 configs/rules/delivery.yaml
 configs/rules/fold.yaml
 configs/rules/multiplex.yaml

{pen_stack-7.1.3 → pen_stack-7.1.4}/pyproject.toml

@@ -4,7 +4,7 @@ build-backend = "setuptools.build_meta"
 
 [project]
 name = "pen-stack"
-version = "7.1.3"
+version = "7.1.4"
 description = "Open infrastructure for genome writing: the Writable Genome atlas, the Writer Atlas, and the Write Planner."
 readme = "README.md"
 requires-python = ">=3.11"