pen-stack 7.1.6__tar.gz → 7.1.8__tar.gz

{pen_stack-7.1.6 → pen_stack-7.1.8}/CHANGELOG.md

@@ -3,6 +3,54 @@
 All notable changes to PEN-STACK are documented here. This file follows
 [Keep a Changelog](https://keepachangelog.com/).
 
+## [7.1.8] - 2026-06-30 - Writer immunogenicity moves to the Writer Atlas; SpCas9 removed from the writer options
+
+### Changed
+- **The writer enzyme is no longer chosen in the Design Studio; its immunogenicity moves to the Writer Atlas, where
+  writers belong.** The Design Studio's writer dropdown existed only to feed the two writer-as-antigen immune axes
+  (MHC-II + ADA); that duplicated the dedicated Writer Atlas page. Now:
+  - The **Writer enzyme dropdown is removed** from `DesignForm` (and `DEFAULT_DESIGN`). The Design Studio's "Profile
+    immune & delivery" action correctly scopes to the **delivery/vehicle** axes (genotoxicity, CD8 capsid, innate,
+    pre-existing NAb, anti-PEG). `ImmuneProfileCard` hides the writer axes by default (`hideWriterAxes`).
+  - A new **Writer immunogenicity** card on the **Writer Atlas** surfaces each genome writer's MHC-II/CD4 epitope
+    load + ADA risk + human self-match, read from the **committed NetMHCIIpan-4.0 cache — not recomputed**
+    (`GET /api/writer/immune`, `immune_profile.writer_immunogenicity_table()`).
+  - **SpCas9 is removed** from the writer set: it is a nuclease/editor, not a large-cargo genome writer. The Writer
+    Atlas immunogenicity covers the actual writers — **Bxb1** (serine integrase) and **ISCro4** (bridge recombinase);
+    the Cas9 nuclease and the human self control are excluded. (The engine retains SpCas9 in its cache for other
+    uses; only the user-facing writer list drops it.)
+- The engine still returns the `mhc2_writer` / `ada_writer` axes from `immune_profile()` for API/MCP callers that
+  pass a `writer_family` — only the web UI moved the writer profiling to the Writer Atlas. No data was recomputed.
+
+### Added
+- `test_ws_profile.py`: `test_writer_immunogenicity_table_for_the_writer_atlas` (covers Bxb1 + ISCro4 from the
+  cache; SpCas9 and the self control excluded; grounded MHC-II + ADA values).
+
+## [7.1.7] - 2026-06-30 - Administration context (in-vivo / ex-vivo) now drives the immune profile
+
+### Fixed
+- **The in-vivo / ex-vivo "Context" toggle had no effect on the immune profile.** It already drove the Generate
+  vehicle sweep (route-compatible vehicles) and the Verify germline-prohibition legality rule, but `immune_profile()`
+  ignored it, so the per-axis immune profile was identical for in-vivo and ex-vivo. It now applies a documented,
+  grounded administration modifier (`immune_profile._administration_modifier` / `_apply_administration`):
+  - **Pre-existing NAb is muted to "no barrier" (1.0) ex vivo.** Ex-vivo delivery (cells transduced in a dish and
+    washed before transplant) never exposes the vector to the patient's circulating antibodies, so pre-existing
+    anti-vector NAb does not gate eligibility — the eligibility fraction is 1.0 regardless of titer. The original
+    seroprevalence value is preserved (`pre_admin_value`) and the muting is explained in the axis note. This is the
+    same in-vivo/ex-vivo distinction the v5.1 `delivery_immunology` profile already encodes (`computed_ex_vivo_muted`).
+  - **CD8 capsid is flagged muted ex vivo** (systemic anti-capsid response minimal), but its intrinsic presentability
+    value is kept — transduced cells can still present capsid epitopes, a real residual concern, so no number is
+    fabricated.
+  - **Genotoxicity, innate, anti-PEG and the writer axes are unchanged** by administration context (insertional risk
+    and cargo/writer immunogenicity are intrinsic, not a function of circulating-antibody exposure).
+  - A `administration_modifier` block (parallel to the existing `route_modifier`) is added to the profile; the
+    `ImmuneProfileCard` shows an in-vivo/ex-vivo chip, a per-axis "ex-vivo muted" badge with the reason, and the
+    administration effect line. In-vivo and unspecified contexts leave every axis untouched (backward compatible).
+
+### Added
+- `test_ws_profile.py`: `test_administration_context_mutes_vector_facing_axes_ex_vivo` (ex-vivo mutes pre-existing
+  NAb to 1.0 and flags CD8; in-vivo/unspecified are unchanged; genotoxicity is never muted by administration).
+
 ## [7.1.6] - 2026-06-30 - Immune axes wired end-to-end + Delivery folded into Design Studio
 
 ### Fixed

{pen_stack-7.1.6 → pen_stack-7.1.8}/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: 7.1.6
+version: 7.1.8
 date-released: 2026-06-30
 authors:
   - family-names: "Mahaboob Ali"

{pen_stack-7.1.6 → pen_stack-7.1.8}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.1.6
+Version: 7.1.8
 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-7.1.6 → pen_stack-7.1.8}/pen_stack/__init__.py

@@ -1,2 +1,2 @@
 """PEN-STACK v3.0 - open infrastructure for genome writing."""
-__version__ = "7.1.6"
+__version__ = "7.1.8"

{pen_stack-7.1.6 → pen_stack-7.1.8}/pen_stack/planner/immune_profile.py

@@ -48,6 +48,65 @@ def _route_modifier(route: str | None) -> dict | None:
             "note": "DOCUMENTED qualitative modifier on the realized response, NOT a quantified magnitude "
                     "(the magnitude stays a known-unknown)."}
 
+
+# v7.1.7 WS-ADMIN, administration-context (in-vivo vs ex-vivo) modifier on the VECTOR-FACING immune axes.
+# Ex-vivo delivery (cells transduced in a dish and washed before transplant) does NOT expose the vector to the
+# patient's circulating antibodies, so the pre-existing anti-vector NAb axis - a humoral, bloodstream eligibility
+# barrier - does not gate ex-vivo use (it is muted to "no barrier"). The systemic anti-capsid CD8 response is also
+# muted ex vivo (the host barely sees the capsid), but transduced cells can still present capsid epitopes (a real,
+# residual concern), so that axis is FLAGGED muted without overwriting its intrinsic value. This is the SAME
+# in-vivo/ex-vivo distinction the v5.1 delivery_immunology profile already encodes ("computed_ex_vivo_muted").
+# A DOCUMENTED, mechanistic modifier - never a fabricated magnitude; the realized response stays a known-unknown.
+_EX_VIVO_MUTED_AXES = ("preexisting_nab", "cd8_epitope")
+
+
+def _is_ex_vivo(in_vivo) -> bool:
+    return str(in_vivo).strip().lower() in ("false", "0", "no", "ex_vivo", "ex vivo", "exvivo")
+
+
+def _administration_modifier(in_vivo) -> dict | None:
+    """Documented administration-context modifier (in-vivo / ex-vivo) on the vector-facing axes, or None when the
+    design does not state an administration context. Qualitative, never a fabricated magnitude."""
+    if in_vivo is None:
+        return None
+    if _is_ex_vivo(in_vivo):
+        return {"context": "ex_vivo", "muted_axes": list(_EX_VIVO_MUTED_AXES),
+                "effect": "ex-vivo administration: the vector contacts cells in a dish and is washed before "
+                          "transplant, so it is not exposed to the patient's circulating antibodies. Pre-existing "
+                          "anti-vector NAb does not gate eligibility (humoral barrier bypassed); the systemic "
+                          "anti-capsid CD8 response is muted, though transduced cells may still present capsid "
+                          "epitopes (a residual, separate consideration).",
+                "note": "DOCUMENTED qualitative administration modifier (the same in-vivo/ex-vivo distinction as the "
+                        "v5.1 delivery profile); the realized immune MAGNITUDE remains a known-unknown."}
+    return {"context": "in_vivo", "muted_axes": [],
+            "effect": "in-vivo (systemic / local) administration: the vector is exposed to the patient's "
+                      "circulating antibodies and immune system, so the pre-existing NAb and anti-capsid CD8 "
+                      "axes apply as reported.",
+            "note": "DOCUMENTED qualitative administration modifier; the realized magnitude is a known-unknown."}
+
+
+def _apply_administration(axes: dict, admin: dict | None) -> None:
+    """Mutate the vector-facing axes in place for an ex-vivo administration context. Pre-existing NAb is muted to
+    'no barrier' (eligibility not gated when the vector never meets circulating antibody); CD8 capsid is flagged
+    muted but its intrinsic value is kept (transduced cells can still present). No-op for in-vivo / unspecified."""
+    if not admin or admin.get("context") != "ex_vivo":
+        return
+    na = axes.get("preexisting_nab")
+    if na and na.get("available") and na.get("value") is not None:
+        na["pre_admin_value"] = na["value"]
+        na["value"] = 1.0
+        na["uncertainty"] = 0.0
+        na["administration_muted"] = True
+        na["note"] = (f"ex-vivo administration: pre-existing circulating anti-vector antibodies do not reach the "
+                      f"vector (transduction in a dish), so pre-existing NAb does not gate eligibility "
+                      f"(muted from {na['pre_admin_value']} to 1.0 = no barrier). " + (na.get("note") or ""))
+    cd = axes.get("cd8_epitope")
+    if cd and cd.get("available") and cd.get("value") is not None:
+        cd["administration_muted"] = True
+        cd["note"] = ("ex-vivo administration: the systemic anti-capsid CD8 response is muted (minimal host capsid "
+                      "exposure); transduced cells may still present capsid epitopes, so the intrinsic value is "
+                      "kept. " + (cd.get("note") or ""))
+
 # headline score key inside each oracle's value dict, per axis.
 _SCORE_KEY = {"genotoxicity": "genotox_score", "cd8_epitope": "capsid_immune_score",
               "innate": "innate_score", "preexisting_nab": "preexisting_score",
@@ -127,6 +186,24 @@ def _writer_antigen_card(design: dict) -> dict | None:
                     "Population-level proxy; realized CD4 response / ADA titer is a known-unknown."}
 
 
+# Genome-WRITER families surfaced in the Writer Atlas immunogenicity view: the bundled writers that are actual
+# genome writers (integrase / recombinase), each with a committed real NetMHCIIpan-4.0 MHC-II load + ADA-risk cache.
+# The Cas9 nuclease (an editor, not a large-cargo writer) and the human self control are intentionally excluded.
+_WRITER_IMMUNE_FAMILIES = ("serine_integrase", "bridge_IS110")
+
+
+def writer_immunogenicity_table() -> list[dict]:
+    """Per-writer immunogenicity (MHC-II/CD4 epitope load + ADA risk) for the bundled genome-writer families, read
+    from the committed NetMHCIIpan-4.0 cache (no recomputation). Surfaced in the Writer Atlas as the writer's
+    antigen profile. Reuses the v6.9 writer-as-antigen card; excludes the Cas9 nuclease and the self control."""
+    out = []
+    for fam in _WRITER_IMMUNE_FAMILIES:
+        card = _writer_antigen_card({"writer_family": fam})
+        if card:
+            out.append({"writer_family": fam, **card})
+    return out
+
+
 def immune_profile(design: dict) -> dict:
     """Per-design immune-risk profile across all axes. ``design`` keys: ``delivery_vehicle`` (or ``vehicle``),
     ``serotype``, ``cargo_seq``, ``writer_output_form`` (or ``cargo_form``), ``pegylated``.
@@ -162,6 +239,11 @@ def immune_profile(design: dict) -> dict:
                                   "no bundled writer sequence -> abstains", "ada_writer"),
     }
 
+    # v7.1.7 administration context: ex-vivo delivery bypasses the patient's circulating antibodies, so the
+    # vector-facing axes (pre-existing NAb, capsid CD8) are muted - documented, not a fabricated magnitude.
+    admin = _administration_modifier(design.get("in_vivo"))
+    _apply_administration(axes, admin)
+
     # writer-as-antigen comparison: for non-viral delivery (no foreign capsid) or a foreign writer outscoring the
     # capsid, the WRITER is the dominant antigen, the v6.9 insight, never collapsed into the other axes.
     dominant = None
@@ -180,6 +262,7 @@ def immune_profile(design: dict) -> dict:
         "writer_as_antigen": ({**writer_card, "dominant_antigen": dominant,
                                "writer_dominant_risk": writer_dominant_risk} if writer_card else None),
         "route_modifier": _route_modifier(design.get("route")), # v5.6 WS-EXT documented route modifier (or None)
+        "administration_modifier": admin, # v7.1.7 in-vivo / ex-vivo documented modifier on the vector-facing axes
         "known_unknowns": KNOWN_UNKNOWNS,
         "no_fabrication": True,
         "note": ("relative immune-risk SCREEN across axes (now incl. CD4/MHC-II + ADA over the writer enzyme); each "

{pen_stack-7.1.6 → pen_stack-7.1.8}/pen_stack/server/api.py

@@ -244,6 +244,22 @@ def writer_variants_endpoint(integrase: str | None = None, system: str | None =
                     "(reported as a known limitation, never a manufactured positive)."}
 
 
+@app.get("/writer/immune", tags=["writer atlas"])
+def writer_immune_endpoint():
+    """The writer enzyme's immunogenicity as an antigen (v6.9 writer-as-antigen, surfaced in the Writer Atlas from
+    v7.1.8): per genome-writer family, the real NetMHCIIpan-4.0 MHC-II/CD4 epitope load + the ADA-risk axis
+    (MHC-II density x foreignness, self-tolerance filtered against the human proteome). Read from the committed
+    cache - NOT recomputed. Population-level proxy, never a patient-specific magnitude (a known-unknown). The Cas9
+    nuclease (an editor, not a large-cargo writer) and the human self control are excluded."""
+    from pen_stack.planner.immune_profile import writer_immunogenicity_table
+    return {"writers": writer_immunogenicity_table(),
+            "method": "NetMHCIIpan-4.0 MHC-II epitope load + ADA risk (MHC-II density x foreignness, self-tolerance "
+                      "filtered against the human proteome). Population-level proxy from the committed cache; the "
+                      "realized CD4 response / ADA titer is a known-unknown.",
+            "scale": "0-1, higher = lower risk (1 = least presentable / least ADA-driving)",
+            "no_fabrication": True}
+
+
 @app.get("/bridge/design")
 def bridge_design(target: str, donor: str, scaffold: str = "ISCro4_enhanced",
                   ct: str | None = None, scan: bool = False):

{pen_stack-7.1.6 → pen_stack-7.1.8}/pen_stack.egg-info/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: pen-stack
-Version: 7.1.6
+Version: 7.1.8
 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-7.1.6 → pen_stack-7.1.8}/pyproject.toml

@@ -4,7 +4,7 @@ build-backend = "setuptools.build_meta"
 
 [project]
 name = "pen-stack"
-version = "7.1.6"
+version = "7.1.8"
 description = "Open infrastructure for genome writing: the Writable Genome atlas, the Writer Atlas, and the Write Planner."
 readme = "README.md"
 requires-python = ">=3.11"