{
 "cells": [
  {
   "cell_type": "markdown",
   "id": "2f04eee0-5928-4e74-a754-6dc2e528810c",
   "metadata": {},
   "source": [
    "# epiTOC1"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "a3f514a3-772c-4a14-afdf-5a8376851ff4",
   "metadata": {},
   "source": [
    "## Index\n",
    "1. [Instantiate model class](#Instantiate-model-class)\n",
    "2. [Define clock metadata](#Define-clock-metadata)\n",
    "3. [Download clock dependencies](#Download-clock-dependencies)\n",
    "5. [Load features](#Load-features)\n",
    "6. [Load weights into base model](#Load-weights-into-base-model)\n",
    "7. [Load reference values](#Load-reference-values)\n",
    "8. [Load preprocess and postprocess objects](#Load-preprocess-and-postprocess-objects)\n",
    "10. [Check all clock parameters](#Check-all-clock-parameters)\n",
    "10. [Basic test](#Basic-test)\n",
    "11. [Save torch model](#Save-torch-model)\n",
    "12. [Clear directory](#Clear-directory)"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "d95fafdc-643a-40ea-a689-200bd132e90c",
   "metadata": {},
   "source": [
    "Let's first import some packages:"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "4adfb4de-cd79-4913-a1af-9e23e9e236c9",
   "metadata": {},
   "outputs": [],
   "source": [
    "import os\n",
    "import inspect\n",
    "import shutil\n",
    "import json\n",
    "import torch\n",
    "import pandas as pd\n",
    "import pyaging as pya"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "145082e5-ced4-47ae-88c0-cb69773e3c5a",
   "metadata": {},
   "source": [
    "## Instantiate model class"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "id": "8aa77372-7ed3-4da7-abc9-d30372106139",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "class epiTOC1(pyagingModel):\n",
      "    def __init__(self):\n",
      "        super().__init__()\n",
      "\n",
      "    def preprocess(self, x):\n",
      "        # Filter out -1 values per row and calculate the mean per row\n",
      "        means = []\n",
      "        for row in x:\n",
      "            filtered_row = row[row != -1]\n",
      "            if len(filtered_row) > 0:\n",
      "                mean = torch.mean(filtered_row)\n",
      "            else:\n",
      "                mean = torch.tensor(float('nan'))\n",
      "            means.append(mean)\n",
      "        return torch.vstack(means)\n",
      "\n",
      "    def postprocess(self, x):\n",
      "        return x\n",
      "\n"
     ]
    }
   ],
   "source": [
    "def print_entire_class(cls):\n",
    "    source = inspect.getsource(cls)\n",
    "    print(source)\n",
    "\n",
    "print_entire_class(pya.models.epiTOC1)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "78536494-f1d9-44de-8583-c89a310d2307",
   "metadata": {},
   "outputs": [],
   "source": [
    "model = pya.models.epiTOC1()"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "51f8615e-01fa-4aa5-b196-3ee2b35d261c",
   "metadata": {},
   "source": [
    "## Define clock metadata"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "6601da9e-8adc-44ee-9308-75e3cd31b816",
   "metadata": {},
   "outputs": [],
   "source": [
    "model.metadata[\"clock_name\"] = \"epitoc1\"\n",
    "model.metadata[\"data_type\"] = \"DNA methylation\"  # Paper: The study constructs clocks from DNA methylation measurements.\n",
    "model.metadata[\"species\"] = \"Homo sapiens\"  # Paper: The analyzed samples and clock are human.\n",
    "model.metadata[\"year\"] = 2016\n",
    "model.metadata[\"approved_by_author\"] = \"⌛\"\n",
    "model.metadata[\"citation\"] = \"Yang, Zhen, et al. \\\"Correlation of an epigenetic mitotic clock with cancer risk.\\\" Genome Biology 17 (2016): 205.\"\n",
    "model.metadata[\"doi\"] = \"https://doi.org/10.1186/s13059-016-1064-3\"\n",
    "model.metadata[\"notes\"] = \"Relative mitotic-age score equal to the mean beta value across 385 polycomb-target promoter CpGs; it is not an absolute division count.\"\n",
    "model.metadata[\"research_only\"] = None\n",
    "model.metadata[\"tissue\"] = [\"multi-tissue\", \"whole blood\"]  # Paper: Fetal tissues established an unmethylated ground state and Hannum whole blood established age gain.\n",
    "model.metadata[\"predicts\"] = [\"mitotic age\"]  # Paper: The score is a relative estimate of stem-cell divisions per stem cell.\n",
    "model.metadata[\"training_target\"] = [\"chronological age\"]  # Paper: The 385 sites were selected for age-associated hypermethylation in healthy blood.\n",
    "model.metadata[\"unit\"] = [\"beta value\"]  # Paper: pcgtAge is the average beta value over the 385 selected CpGs.\n",
    "model.metadata[\"model_type\"] = \"mean methylation aggregation\"  # Paper: The score is calculated as an unweighted average of selected CpG beta values.\n",
    "model.metadata[\"platform\"] = [\"Illumina 450K\"]  # Paper: The derivation data and selected probes were from Illumina 450K methylation profiles.\n",
    "model.metadata[\"population\"] = \"all ages\"  # Paper: Model derivation combined fetal reference tissues with healthy adult samples from the Hannum whole-blood cohort.\n",
    "model.metadata[\"journal\"] = \"Genome Biology\"\n",
    "model.metadata[\"last_author\"] = \"Andrew E. Teschendorff\"\n",
    "model.metadata[\"n_features\"] = 385\n",
    "model.metadata[\"citations\"] = 357\n",
    "model.metadata[\"citations_date\"] = \"2026-07-05\"\n"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "74492239-5aae-4026-9d90-6bc9c574c110",
   "metadata": {},
   "source": [
    "## Download clock dependencies"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "c07158bc-19c9-47de-8276-5d1dc5361b22",
   "metadata": {},
   "source": [
    "#### Download directly with curl"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "6b57cb84-b940-4cfe-8933-3955cab9dfe9",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "0"
      ]
     },
     "execution_count": 5,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "supplementary_url = \"https://static-content.springer.com/esm/art%3A10.1186%2Fs13059-016-1064-3/MediaObjects/13059_2016_1064_MOESM2_ESM.xls\"\n",
    "supplementary_file_name = \"coefficients.xlsx\"\n",
    "os.system(f\"curl -o {supplementary_file_name} {supplementary_url}\")"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "5035b180-3d1b-4432-8ebe-b9c92bd93a7f",
   "metadata": {},
   "source": [
    "## Load features"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "793d7b24-b1ef-4dd2-ac26-079f7b67fba7",
   "metadata": {},
   "source": [
    "#### From Excel file"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "110a5ded-d25f-4cef-8e84-4f51210dfc26",
   "metadata": {},
   "outputs": [],
   "source": [
    "df = pd.read_excel('coefficients.xlsx', sheet_name='agehyperPCGT-tableS1', skiprows=1)\n",
    "df['feature'] = df['CpG'].astype(str)\n",
    "\n",
    "model.features = df['feature'].tolist()"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ee6d8fa0-4767-4c45-9717-eb1c95e2ddc0",
   "metadata": {},
   "source": [
    "## Load weights into base model"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "e09b3463-4fd4-41b1-ac21-e63ddd223fe0",
   "metadata": {},
   "outputs": [],
   "source": [
    "weights = torch.tensor([1.0]).unsqueeze(0)\n",
    "intercept = torch.tensor([0.0])"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ad261636-5b00-4979-bb1d-67a851f7aa19",
   "metadata": {},
   "source": [
    "#### Linear model"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "d7f43b99-26f2-4622-9a76-316712058877",
   "metadata": {},
   "outputs": [],
   "source": [
    "base_model = pya.models.LinearModel(input_dim=len(model.features))\n",
    "\n",
    "base_model.linear.weight.data = weights.float()\n",
    "base_model.linear.bias.data = intercept.float()\n",
    "\n",
    "model.base_model = base_model"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "ad8b4c1d-9d57-48b7-9a30-bcfea7b747b1",
   "metadata": {},
   "source": [
    "## Load reference values"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "id": "ade0f4c9-2298-4fc3-bb72-d200907dd731",
   "metadata": {},
   "outputs": [],
   "source": [
    "model.reference_values = [-1]*len(model.features)"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "af3bcf7b-74a8-4d21-9ccb-4de0c2b0516b",
   "metadata": {},
   "source": [
    "## Load preprocess and postprocess objects"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "id": "7a22fb20-c605-424d-8efb-7620c2c0755c",
   "metadata": {},
   "outputs": [],
   "source": [
    "model.preprocess_name = \"mean\"\n",
    "model.preprocess_dependencies = None"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "id": "ff4a21cb-cf41-44dc-9ed1-95cf8aa15772",
   "metadata": {},
   "outputs": [],
   "source": [
    "model.postprocess_name = None\n",
    "model.postprocess_dependencies = None"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "86e3d6b1-e67e-4f3d-bd39-0ebec5726c3c",
   "metadata": {},
   "source": [
    "## Check all clock parameters"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "id": "2168355c-47d9-475d-b816-49f65e74887c",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "\n",
      "%==================================== Model Details ====================================%\n",
      "Model Attributes:\n",
      "\n",
      "training: True\n",
      "metadata: {'approved_by_author': '⌛',\n",
      " 'citation': 'Yang, Zhen, et al. \"Correlation of an epigenetic mitotic clock '\n",
      "             'with cancer risk.\" Genome biology 17 (2016): 1-18.',\n",
      " 'clock_name': 'epitoc1',\n",
      " 'data_type': 'methylation',\n",
      " 'doi': 'https://doi.org/10.1186/s13059-016-1064-3',\n",
      " 'notes': 'The reference values are simply -1 for the algorithm to ignore '\n",
      "          'them.',\n",
      " 'research_only': None,\n",
      " 'species': 'Homo sapiens',\n",
      " 'version': None,\n",
      " 'year': 2016}\n",
      "reference_values: [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]... [Total elements: 385]\n",
      "preprocess_name: 'mean'\n",
      "preprocess_dependencies: None\n",
      "postprocess_name: None\n",
      "postprocess_dependencies: None\n",
      "features: ['cg00043095', 'cg00060320', 'cg00181968', 'cg00329270', 'cg00347369', 'cg00397986', 'cg00466268', 'cg00665492', 'cg00884606', 'cg00916884', 'cg00930628', 'cg00962913', 'cg01050423', 'cg01185626', 'cg01435574', 'cg01537995', 'cg01587896', 'cg01670677', 'cg01699217', 'cg01783070', 'cg01830294', 'cg02004418', 'cg02056682', 'cg02071825', 'cg02150988', 'cg02160530', 'cg02186542', 'cg02266732', 'cg02315940', 'cg02554246']... [Total elements: 385]\n",
      "base_model_features: None\n",
      "\n",
      "%==================================== Model Details ====================================%\n",
      "Model Structure:\n",
      "\n",
      "base_model: LinearModel(\n",
      "  (linear): Linear(in_features=385, out_features=1, bias=True)\n",
      ")\n",
      "\n",
      "%==================================== Model Details ====================================%\n",
      "Model Parameters and Weights:\n",
      "\n",
      "base_model.linear.weight: tensor([[1.]])\n",
      "base_model.linear.bias: tensor([0.])\n",
      "\n",
      "%==================================== Model Details ====================================%\n",
      "\n"
     ]
    }
   ],
   "source": [
    "pya.utils.print_model_details(model)"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "986d0262-e0c7-4036-b687-dee53ba392fb",
   "metadata": {},
   "source": [
    "## Basic test"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "id": "936b9877-d076-4ced-99aa-e8d4c58c5caf",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "tensor([[ 0.0669],\n",
       "        [-0.0019],\n",
       "        [ 0.0772],\n",
       "        [ 0.0336],\n",
       "        [-0.1134],\n",
       "        [-0.0825],\n",
       "        [-0.0375],\n",
       "        [-0.0160],\n",
       "        [-0.0543],\n",
       "        [-0.0141]], dtype=torch.float64, grad_fn=<AddmmBackward0>)"
      ]
     },
     "execution_count": 13,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "torch.manual_seed(42)\n",
    "input = torch.randn(10, len(model.features), dtype=float)\n",
    "model.eval()\n",
    "model.to(float)\n",
    "pred = model(input)\n",
    "pred"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "fe8299d7-9285-4e22-82fd-b664434b4369",
   "metadata": {},
   "source": [
    "## Save torch model"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "id": "5ef2fa8d-c80b-4fdd-8555-79c0d541788e",
   "metadata": {},
   "outputs": [],
   "source": [
    "torch.save(model, f\"../weights/{model.metadata['clock_name']}.pt\")"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "bac6257b-8d08-4a90-8d0b-7f745dc11ac1",
   "metadata": {},
   "source": [
    "## Clear directory\n",
    "<a id=\"10\"></a>"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "id": "11aeaa70-44c0-42f9-86d7-740e3849a7a6",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Deleted file: coefficients.xlsx\n",
      "Deleted folder: .ipynb_checkpoints\n"
     ]
    }
   ],
   "source": [
    "# Function to remove a folder and all its contents\n",
    "def remove_folder(path):\n",
    "    try:\n",
    "        shutil.rmtree(path)\n",
    "        print(f\"Deleted folder: {path}\")\n",
    "    except Exception as e:\n",
    "        print(f\"Error deleting folder {path}: {e}\")\n",
    "\n",
    "# Get a list of all files and folders in the current directory\n",
    "all_items = os.listdir('.')\n",
    "\n",
    "# Loop through the items\n",
    "for item in all_items:\n",
    "    # Check if it's a file and does not end with .ipynb\n",
    "    if os.path.isfile(item) and not item.endswith('.ipynb'):\n",
    "        os.remove(item)\n",
    "        print(f\"Deleted file: {item}\")\n",
    "    # Check if it's a folder\n",
    "    elif os.path.isdir(item):\n",
    "        remove_folder(item)"
   ]
  }
 ],
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