GRASP One-Shot Designer (Colab / PyPI)

grasp_oneshot_designer.ipynb

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   "cell_type": "markdown",
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    "# GRASP One-Shot Designer\n",
    "\n",
    "Design Golden Gate oligos for a binder that recognizes **one target RNA**.\n",
    "\n",
    "Flow: RNA → protein → free cut sites → optimized oligos.\n",
    "\n",
    "1. Run **0 · Install** once  \n",
    "2. Fill the forms below and run each cell top → bottom  \n",
    "\n",
    "Code is hidden by default (Colab Forms). Cell ⋮ → **Form → Hide code** if needed.\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#@title 0 · Install (PyPI) { display-mode: \"form\" }\n",
    "#@markdown Installs everything from PyPI. No GitHub token needed. Re-run if imports fail after a runtime restart.\n",
    "\n",
    "%pip install -q -U \"grasp-library-designer>=0.1.0\"\n",
    "\n",
    "import importlib\n",
    "import grasp_library\n",
    "from importlib.metadata import version\n",
    "\n",
    "print(\"grasp-library-designer\", version(\"grasp-library-designer\"))\n",
    "print(\"import ok:\", grasp_library.__name__)\n"
   ]
  },
  {
   "cell_type": "code",
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    "#@title 1 · Settings { display-mode: \"form\" }\n",
    "#@markdown Choose organism, synthesis, ligation, and target RNA — then run this cell.\n",
    "\n",
    "target_rna = \"UUACACGUG\" #@param {type:\"string\"}\n",
    "organism = \"Escherichia coli (Kazusa)\" #@param [\"Escherichia coli (Kazusa)\", \"Saccharomyces cerevisiae (Kazusa)\", \"Homo sapiens (Kazusa)\", \"Euglena gracilis nuclear (Kazusa)\", \"Chlamydomonas reinhardtii nuclear (Kazusa)\", \"Chlamydomonas reinhardtii chloroplast (Kazusa)\"]\n",
    "genetic_code = 1 #@param {type:\"integer\"}\n",
    "synthesis_vendor = \"Twist · Standard gene guidelines\" #@param [\"Twist · Express / Low complexity\", \"Twist · Standard gene guidelines\", \"Twist · Complex Genes tolerant\", \"IDT · gBlocks / eBlocks conservative\", \"Generic · conservative (default)\"]\n",
    "assembly_enzyme = \"GRASP default · BsaI + BpiI + BsmBI\" #@param [\"GRASP default · BsaI + BpiI + BsmBI\", \"BsaI (GGTCTC)\", \"BpiI / BbsI (GAAGAC)\", \"BsmBI / Esp3I (CGTCTC)\", \"None (no enzyme filter)\"]\n",
    "ligation_table = \"T4 · 18 h · 25 °C (Potapov)\" #@param [\"T4 · 18 h · 25 °C (Potapov)\", \"T4 · 18 h · 37 °C (Potapov)\", \"T4 · 1 h · 25 °C (Potapov)\", \"BsaI-HFv2 · constant 37 °C\", \"BsmBI-v2 · constant 42 °C\"]\n",
    "optimize_depth = 2000 #@param {type:\"integer\"}\n",
    "n_fragments = 0 #@param {type:\"integer\"}\n",
    "#@markdown `n_fragments = 0` means auto (from oligo length limits).\n",
    "\n",
    "from grasp_library import build_default_config, materialize_project\n",
    "from grasp_library.colab_forms import apply_form_settings\n",
    "from grasp_library import notebook_ui as ui\n",
    "\n",
    "PROJECT_DIR = materialize_project()\n",
    "INPUT_DIR = PROJECT_DIR / \"input\"\n",
    "OUTPUT_ROOT = PROJECT_DIR / \"output\" / \"oneshot\"\n",
    "OUTPUT_ROOT.mkdir(parents=True, exist_ok=True)\n",
    "\n",
    "CONFIG = build_default_config(INPUT_DIR)\n",
    "CONFIG[\"project_name\"] = \"GRASP_oneshot_colab\"\n",
    "\n",
    "applied = apply_form_settings(\n",
    "    CONFIG,\n",
    "    organism=organism,\n",
    "    genetic_code=int(genetic_code),\n",
    "    target_rna=target_rna,\n",
    "    synthesis_vendor=synthesis_vendor,\n",
    "    assembly_enzyme=assembly_enzyme,\n",
    "    ligation_table=ligation_table,\n",
    "    optimize_depth=int(optimize_depth),\n",
    "    n_fragments=int(n_fragments) if int(n_fragments) > 0 else None,\n",
    "    overhang_redesign=False,\n",
    ")\n",
    "CONFIG = applied[\"config\"]\n",
    "CODON_DATA = applied[\"codon_data\"]\n",
    "ONESHOT = None\n",
    "\n",
    "ui.status(\n",
    "    f\"Target <b>{CONFIG['target_rna']}</b> · organism <b>{organism}</b> · \"\n",
    "    f\"depth <b>{CONFIG['optimizer']['iterations_per_part']:,}</b> · \"\n",
    "    f\"vendor <b>{CONFIG['synthesis_vendor']}</b><br/>\"\n",
    "    f\"Project → <code>{PROJECT_DIR}</code>\"\n",
    ")\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#@title 2 · Preview binder protein { display-mode: \"form\" }\n",
    "\n",
    "from grasp_library import describe_binder, suggest_fragment_count\n",
    "from grasp_library import notebook_ui as ui\n",
    "\n",
    "info = describe_binder(CONFIG[\"target_rna\"])\n",
    "n_auto = suggest_fragment_count(info[\"cds_length\"])\n",
    "ui.status(\n",
    "    f\"<b>{info['target_rna']}</b> · PPR <code>{info['ppr_code']}</code> · \"\n",
    "    f\"<b>{info['aa_length']}</b> aa · <b>{info['cds_length']}</b> nt · \"\n",
    "    f\"auto fragments ≈ <b>{n_auto}</b>\"\n",
    ")\n",
    "print(info[\"aa_sequence\"])\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#@title 3 · Design oligos { display-mode: \"form\" }\n",
    "#@markdown Re-run after changing settings. Files appear under `grasp_library_project/output/oneshot/`.\n",
    "\n",
    "RUN_ONESHOT = True #@param {type:\"boolean\"}\n",
    "SEED = 42 #@param {type:\"integer\"}\n",
    "\n",
    "import random\n",
    "import numpy as np\n",
    "from IPython.display import display\n",
    "from grasp_library import LigationFidelityCalculator, run_oneshot_design, sanitize_rna_name\n",
    "from grasp_library import notebook_ui as ui\n",
    "\n",
    "random.seed(int(SEED))\n",
    "np.random.seed(int(SEED))\n",
    "\n",
    "ONESHOT = None\n",
    "if not RUN_ONESHOT:\n",
    "    ui.note(\"RUN_ONESHOT is off.\")\n",
    "elif not CODON_DATA:\n",
    "    ui.note(\"Run the Settings cell first.\")\n",
    "else:\n",
    "    rna = sanitize_rna_name(CONFIG[\"target_rna\"])\n",
    "    out_dir = OUTPUT_ROOT / rna\n",
    "    lig = CONFIG[\"ligation\"]\n",
    "    fidelity = LigationFidelityCalculator(\n",
    "        temperature=lig[\"temperature\"],\n",
    "        hours=lig[\"hours\"],\n",
    "        ligation_table=lig.get(\"ligation_table\"),\n",
    "        min_efficiency=lig.get(\"min_efficiency\", 0.25),\n",
    "        min_fidelity=lig.get(\"min_fidelity\", 0.9),\n",
    "    )\n",
    "    n_frag = CONFIG.get(\"oneshot_n_fragments\")\n",
    "    ONESHOT = run_oneshot_design(\n",
    "        target_rna=CONFIG[\"target_rna\"],\n",
    "        codon_data=CODON_DATA,\n",
    "        config=CONFIG,\n",
    "        output_dir=out_dir,\n",
    "        seed=int(SEED),\n",
    "        n_fragments=n_frag,\n",
    "        fidelity=fidelity,\n",
    "        log=print,\n",
    "    )\n",
    "    display(ONESHOT[\"gga_plan\"][\n",
    "        [\"fragment_id\", \"aa_start_0based\", \"aa_end_0based\", \"oh5\", \"oh3\", \"ligation_fidelity_set\"]\n",
    "    ])\n",
    "    cols = [c for c in [\n",
    "        \"fragment_id\", \"assembly_order\", \"oligo_length\", \"oligo_gc\",\n",
    "        \"qc_passed\", \"oligo_sequence_5to3\",\n",
    "    ] if c in ONESHOT[\"oligos\"].columns]\n",
    "    display(ONESHOT[\"oligos\"][cols])\n",
    "    asm = ONESHOT[\"assembled\"]\n",
    "    ui.status(\n",
    "        f\"Translation verified: <b>{asm['translation_verified']}</b> · \"\n",
    "        f\"ligation fidelity <b>{asm['ligation_fidelity']:.4f}</b> · \"\n",
    "        f\"oligos → <code>{ONESHOT['oligo_csv']}</code>\"\n",
    "    )\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#@title 4 · Export Excel { display-mode: \"form\" }\n",
    "\n",
    "import pandas as pd\n",
    "from grasp_library import notebook_ui as ui\n",
    "\n",
    "if ONESHOT is None:\n",
    "    ui.note(\"Run Design first.\")\n",
    "else:\n",
    "    out = ONESHOT[\"output_dir\"]\n",
    "    xlsx = out / f\"oneshot_{ONESHOT['target_rna']}.xlsx\"\n",
    "    with pd.ExcelWriter(xlsx) as writer:\n",
    "        pd.DataFrame([ONESHOT[\"binder\"]]).to_excel(writer, sheet_name=\"binder\", index=False)\n",
    "        ONESHOT[\"gga_plan\"].to_excel(writer, sheet_name=\"gga_plan\", index=False)\n",
    "        ONESHOT[\"oligos\"].to_excel(writer, sheet_name=\"oligos\", index=False)\n",
    "        pd.DataFrame([ONESHOT[\"summary\"]]).to_excel(writer, sheet_name=\"summary\", index=False)\n",
    "    ui.status(f\"Wrote <code>{xlsx}</code>\")\n",
    "    if \"google.colab\" in __import__(\"sys\").modules:\n",
    "        from google.colab import files\n",
    "        files.download(str(xlsx))\n",
    "    for p in sorted(out.glob(\"*\")):\n",
    "        if p.is_file():\n",
    "            print(p.name)\n"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Notes\n",
    "\n",
    "| Step | What happens |\n",
    "|---|---|\n",
    "| Install | `pip install grasp-library-designer` from PyPI |\n",
    "| RNA → protein | PPR code into GRASP repeat scaffold |\n",
    "| Optimize | Full CDS codon + synthesis fitness |\n",
    "| Cuts | Codon-aligned overhangs for ligation fidelity |\n",
    "| Export | Flanked oligos for Golden Gate |\n",
    "\n",
    "For the **42-module combinatorial library**, open `grasp_library_designer.ipynb`.\n",
    "\n",
    "Package: https://pypi.org/project/grasp-library-designer/\n"
   ]
  }
 ]
}