# PEN-COMPARE Model Card

## Framework Identity

**Name:** PEN-COMPARE TrueWriterScore v3.2  
**Version:** 0.1.0  
**Date:** 2026-05-26  
**Authors:** Anees Ahmed Mahaboob Ali (ahmedaneesm@gmail.com)  
**License:** MIT  
**Pre-registration:** https://osf.io/4kdvy

## Purpose

PEN-COMPARE certifies genome editors as TRUE_WRITER, PROBABLE_WRITER,
EMERGING_WRITER, or NOT_WRITER using a 5-gate hierarchical scoring system.
The framework operationalizes the **Molecular Pen hypothesis**: that IS110
bridge recombinases are non-destructive precision writers that avoid
double-strand DNA breaks.

## Inputs

| Field | Type | Description |
|---|---|---|
| s_dsb | float [0,1] | DSB-avoidance axis score from pen-score |
| s_prog | float [0,1] | Programmability axis score |
| s_cargo | float [0,1] | Native cargo capability axis score |
| length_aa | int or None | Protein length in amino acids |
| evidence_sources | list[str] | Subset of {biochemical, structural, computational, cell_based} |
| intrinsic_cargo_mechanism | bool | Whether native (non-template) cargo delivery is confirmed |
| split_aav_eligible | bool | Whether split-AAV packaging has been demonstrated |

## Outputs

| Field | Description |
|---|---|
| tier | TRUE_WRITER / PROBABLE_WRITER / EMERGING_WRITER / NOT_WRITER |
| qualifying_gates_passed | 0–4 |
| has_cell_based_evidence | bool |
| auto_demoted | bool (True only when G1 fails) |
| gate_results | Per-gate pass/fail with observed value and threshold |

## Tier Ladder

```
G1 FAIL  →  NOT_WRITER (auto-demote, final)

G1 PASS  +  4 qualifying  +  cell_based  →  TRUE_WRITER
G1 PASS  +  4 qualifying  +  no cell_based  →  PROBABLE_WRITER
G1 PASS  +  3 qualifying  +  cell_based  →  PROBABLE_WRITER
G1 PASS  +  1–2 qualifying  →  EMERGING_WRITER
G1 PASS  +  0 qualifying  →  NOT_WRITER
```

## Training Data & Calibration

The gates use **no statistical training** — all thresholds are mechanistically
motivated and pre-registered. Calibration anchors:

| Editor | Expected Tier | Verified |
|---|---|---|
| ISCro4 (D2TGM5) | TRUE_WRITER | ✅ |
| IS621 (A0A2X3M8B0) | PROBABLE_WRITER | ✅ |
| Bxb1 | PROBABLE_WRITER (G2 fails) | ✅ |
| SpCas9 (Q99ZW2) | NOT_WRITER (G1 auto-demote) | ✅ |

## Known Limitations

1. **S_Mature > 1.0 pydantic bug:** pen-score clamps AxisScores before validation for SpCas9/PE2/etc.
2. **length_aa = None:** 13 natural editors have no sequence length in pen-score; G4 falls back to split_aav heuristic.
3. **IS621 PenScore discrepancy:** locked predictions_v3.yaml cites 0.929; actual value is 0.9473. Does not affect P2 outcome; must be disclosed in manuscript.
4. **Universe scope:** limited to editors scoreable by pen-score v0.1.3 and pen-assemble v0.5.2 catalog.

## Sensitivity Analysis

18,000-combination parameter sweep (15×15×16×5 grid):
- ISCro4 robustness = **1.000** (stable under all threshold variations)
- Zero boundary cases (robustness < 0.50)
- 4 near-boundary editors (50–80%): Bxb1, eePASSIGE, eePASSIGE_v2, phiC31

## Pre-Registration Outcomes

All 5 predictions PASS (evaluated 2026-05-26):

| ID | Statement | Result |
|---|---|---|
| P1 | ISCro4 sole TRUE_WRITER | ✅ PASS |
| P2 | Zero designs TRUE_WRITER | ✅ PASS |
| P3 | ≥5 triangulation discrepancies | ✅ PASS (30) |
| P4 | RAG LLM ≥80% accuracy | ✅ PASS (88%) |
| P5 | Webserver p95 ≤3s | ✅ PASS (0.01s) |

## Citation

```bibtex
@software{pen_compare_2026,
  author = {Mahaboob Ali, Anees Ahmed},
  title = {PEN-COMPARE: Hierarchical Certification Framework for Non-Destructive Genome Editors},
  version = {0.1.0},
  year = {2026},
  url = {https://github.com/ahmedanees-m/pen-compare},
  note = {Pre-registration: https://osf.io/4kdvy}
}
```