{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [],
   "source": [
    "%config InlineBackend.figure_formats = ['svg']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "import random\n",
    "import numpy as np\n",
    "import pandas as pd\n",
    "from joblib import dump, load\n",
    "np.random.seed(42)\n",
    "random.seed(42)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "data_dir = './data/'\n",
    "with np.load('data/Xy.npz') as f:\n",
    "    X = f['X']\n",
    "    y = f['y']\n",
    "    y34 = f['y34']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Perform temporal split of data into train/test sets\n",
    "pop = pd.read_csv(data_dir + 'population/d10_with_vitals.csv').set_index('BMT_ID')\n",
    "\n",
    "split_date = 201701001\n",
    "split_idx = -85\n",
    "\n",
    "assert (pop[:split_idx].index < split_date).all()\n",
    "assert (pop[split_idx:].index >= split_date).all()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [],
   "source": [
    "from sklearn import preprocessing, model_selection, metrics, utils\n",
    "from sklearn.linear_model import LogisticRegression\n",
    "from tqdm import tqdm\n",
    "from joblib import Parallel, delayed\n",
    "from sklearn.base import clone"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Specify hyperparameters and cv parameters\n",
    "base_estimator = LogisticRegression(penalty='l2', class_weight='balanced', solver='liblinear')\n",
    "param_grid = {\n",
    "    'C': [10. ** n for n in range(-6, 7)],\n",
    "    'penalty': ['l2'],\n",
    "}"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Alternative label definition\n",
    "{0,1,2} -> negative, {3,4} -> positive"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 472,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(0.31790123456790126, 0.13580246913580246)"
      ]
     },
     "execution_count": 472,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "y.mean(), y34.mean()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 376,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/data4/tangsp/venv/lib/python3.7/site-packages/sklearn/model_selection/_search.py:814: DeprecationWarning: The default of the `iid` parameter will change from True to False in version 0.22 and will be removed in 0.24. This will change numeric results when test-set sizes are unequal.\n",
      "  DeprecationWarning)\n"
     ]
    }
   ],
   "source": [
    "Xtr, Xte = X[:split_idx], X[split_idx:]\n",
    "ytr, yte = y34[:split_idx], y34[split_idx:]\n",
    "\n",
    "cv_splits, cv_repeat = 5, 20\n",
    "cv = model_selection.RepeatedStratifiedKFold(cv_splits, cv_repeat, random_state=0)\n",
    "clf = model_selection.GridSearchCV(\n",
    "    clone(base_estimator), param_grid, \n",
    "    cv=cv, scoring='roc_auc', n_jobs=5,\n",
    ")\n",
    "clf.fit(Xtr, ytr)\n",
    "test_score = metrics.roc_auc_score(yte, clf.decision_function(Xte))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 377,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "                                                  \r"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Test AUC: 0.596 (0.423, 0.761)\n"
     ]
    }
   ],
   "source": [
    "y_true = yte\n",
    "y_score = clf.decision_function(Xte)\n",
    "\n",
    "def boostrap_func(i, y_true, y_score):\n",
    "    yte_true_b, yte_pred_b = utils.resample(y_true, y_score, replace=True, random_state=i)\n",
    "    return metrics.roc_curve(yte_true_b, yte_pred_b), metrics.roc_auc_score(yte_true_b, yte_pred_b)\n",
    "\n",
    "roc_curves, auc_scores = zip(*Parallel(n_jobs=4)(delayed(boostrap_func)(i, y_true, y_score) for i in tqdm(range(1000), leave=False)))\n",
    "print('Test AUC: {:.3f} ({:.3f}, {:.3f})'.format(np.median(auc_scores), np.percentile(auc_scores, 2.5), np.percentile(auc_scores, 97.5)))"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Random Forest model"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 378,
   "metadata": {},
   "outputs": [],
   "source": [
    "from sklearn.model_selection import RandomizedSearchCV\n",
    "from sklearn.ensemble import RandomForestClassifier\n",
    "import scipy"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 379,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "RandomizedSearchCV(cv=<sklearn.model_selection._split.RepeatedStratifiedKFold object at 0x7f9b8ffacc50>,\n",
       "                   error_score='raise-deprecating',\n",
       "                   estimator=RandomForestClassifier(bootstrap=True,\n",
       "                                                    class_weight=None,\n",
       "                                                    criterion='gini',\n",
       "                                                    max_depth=None,\n",
       "                                                    max_features='auto',\n",
       "                                                    max_leaf_nodes=None,\n",
       "                                                    min_impurity_decrease=0.0,\n",
       "                                                    min_impurity_split=None,\n",
       "                                                    min_samples_leaf=1,\n",
       "                                                    min_sample...\n",
       "                                        'min_samples_leaf': <scipy.stats._distn_infrastructure.rv_frozen object at 0x7f9b8ffad050>,\n",
       "                                        'min_samples_split': <scipy.stats._distn_infrastructure.rv_frozen object at 0x7f9b8ffadc10>,\n",
       "                                        'n_estimators': <scipy.stats._distn_infrastructure.rv_frozen object at 0x7f9b8ffad490>},\n",
       "                   pre_dispatch='2*n_jobs', random_state=None, refit=True,\n",
       "                   return_train_score=False, scoring='roc_auc', verbose=0)"
      ]
     },
     "execution_count": 379,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "Xtr, Xte = X[:split_idx], X[split_idx:]\n",
    "ytr, yte = y[:split_idx], y[split_idx:]\n",
    "\n",
    "cv_splits, cv_repeat = 5, 20\n",
    "cv = model_selection.RepeatedStratifiedKFold(cv_splits, cv_repeat, random_state=0)\n",
    "clf = RandomizedSearchCV(\n",
    "        RandomForestClassifier(), \n",
    "        {\n",
    "            \"criterion\": [\"gini\", \"entropy\"],\n",
    "            \"max_depth\": [4, 8, 16, 32, None],\n",
    "            \"max_features\": scipy.stats.randint(1, 100),\n",
    "            \"min_samples_split\": scipy.stats.randint(2, 11),\n",
    "            \"min_samples_leaf\": scipy.stats.randint(1, 11),\n",
    "            \"n_estimators\": scipy.stats.randint(50,500),\n",
    "            \"bootstrap\": [True],\n",
    "        },\n",
    "        n_iter=10,\n",
    "        cv=cv,\n",
    "        scoring='roc_auc',\n",
    "        n_jobs=5,\n",
    "    )\n",
    "\n",
    "clf.fit(Xtr, ytr)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 380,
   "metadata": {},
   "outputs": [],
   "source": [
    "test_score = metrics.roc_auc_score(yte, clf.predict_proba(Xte)[:,1])"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 381,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "                                                  \r"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Test AUC: 0.651 (0.525, 0.768)\n"
     ]
    }
   ],
   "source": [
    "y_true = yte\n",
    "y_score = clf.predict_proba(Xte)[:,1]\n",
    "\n",
    "def boostrap_func(i, y_true, y_score):\n",
    "    yte_true_b, yte_pred_b = utils.resample(y_true, y_score, replace=True, random_state=i)\n",
    "    return metrics.roc_curve(yte_true_b, yte_pred_b), metrics.roc_auc_score(yte_true_b, yte_pred_b)\n",
    "\n",
    "_, auc_scores_rf = zip(*Parallel(n_jobs=4)(delayed(boostrap_func)(i, y_true, y_score) for i in tqdm(range(1000), leave=False)))\n",
    "print('Test AUC: {:.3f} ({:.3f}, {:.3f})'.format(np.median(auc_scores_rf), np.percentile(auc_scores_rf, 2.5), np.percentile(auc_scores_rf, 97.5)))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 382,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "                                                    \r"
     ]
    },
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Test AUC: 0.658 (0.536, 0.784)\n"
     ]
    }
   ],
   "source": [
    "clf_main = load('data/model_combined.joblib')\n",
    "y_score = clf_main.predict_proba(Xte)[:,1]\n",
    "_, auc_scores_main = zip(*Parallel(n_jobs=4)(delayed(boostrap_func)(i, y_true, y_score) for i in tqdm(range(1000), leave=False)))\n",
    "print('Test AUC: {:.3f} ({:.3f}, {:.3f})'.format(\n",
    "    np.median(auc_scores_main), np.percentile(auc_scores_main, 2.5), np.percentile(auc_scores_main, 97.5)))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 383,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "0.782"
      ]
     },
     "execution_count": 383,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "# H0: proposed == baseline\n",
    "# H1: proposed != baseline\n",
    "# resampling test, two-sided p-value\n",
    "2 * min(\n",
    "    (np.array(auc_scores_main) < np.array(auc_scores_rf)).mean(),\n",
    "    (np.array(auc_scores_main) > np.array(auc_scores_rf)).mean()\n",
    ")"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Kaplan Meier plot"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [],
   "source": [
    "import matplotlib.pyplot as plt\n",
    "from sklearn import utils"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 482,
   "metadata": {},
   "outputs": [],
   "source": [
    "Xtr, Xte = X[:split_idx], X[split_idx:]\n",
    "ytr, yte = y[:split_idx], y[split_idx:]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 483,
   "metadata": {},
   "outputs": [],
   "source": [
    "pop = pd.read_csv(data_dir + 'population/d10_with_vitals.csv').set_index('BMT_ID')\n",
    "labels = pd.read_csv(data_dir + 'prep/label.csv').set_index('BMT_ID')\n",
    "IDs = pop.index[split_idx:]\n",
    "onset = labels.loc[IDs, 'GVHD_onset_day'].replace(np.nan, np.inf)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 484,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "IntervalIndex([(0.234, 0.539], (0.539, 0.74]],\n",
      "              closed='right',\n",
      "              dtype='interval[float64]')\n"
     ]
    }
   ],
   "source": [
    "clf = load('data/model_combined.joblib')\n",
    "threshold = np.percentile(clf.predict_proba(Xtr)[:,1], [0, 70, 100])\n",
    "y_prob = clf.predict_proba(Xte)[:,1]\n",
    "y_group = pd.cut(y_prob, threshold)\n",
    "print(y_group.categories)\n",
    "y_group = y_group.codes"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 485,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Standard errors calculated via the Greenwood's formula\n",
    "# http://sphweb.bumc.bu.edu/otlt/MPH-Modules/BS/BS704_Survival/BS704_Survival4.html\n",
    "def calculate_survival_curve_se(onset_m, times):\n",
    "    surv_probs = [(onset_m > 0).mean()]\n",
    "    stderrs = [0]\n",
    "    quotients = []\n",
    "    for day in sorted(times):\n",
    "        if np.isfinite(day):\n",
    "            Nt, Dt = (onset_m >= day).sum(), (onset_m == day).sum()\n",
    "            St = (onset_m > day).mean()\n",
    "            quotients.append(Dt / (Nt * (Nt - Dt)))\n",
    "            surv_probs.append(St)\n",
    "            stderrs.append(St * np.sqrt(np.sum(quotients)))\n",
    "    return np.array(surv_probs), np.array(stderrs)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 486,
   "metadata": {},
   "outputs": [
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   ],
   "source": [
    "times = onset.unique()\n",
    "times = times[times <= 105]\n",
    "times = sorted(times)\n",
    "\n",
    "for group in [0,1]:\n",
    "    m = (y_group == group)\n",
    "    o_m = onset[m]\n",
    "    surv_probs, stderrs = calculate_survival_curve_se(o_m, times)\n",
    "    CI = [\n",
    "        np.clip(surv_probs - 1.96 * stderrs, 0, 1), \n",
    "        np.clip(surv_probs + 1.96 * stderrs, 0, 1),\n",
    "    ]\n",
    "    plt.plot([0] + times, surv_probs)\n",
    "    plt.fill_between([0] + times, CI[0], CI[1], alpha=0.12)\n",
    "\n",
    "plt.xlim(0,100)\n",
    "plt.legend(labels=['low risk', 'high risk'])\n",
    "plt.xlabel('Days post-transplant')\n",
    "plt.ylabel('Grade II-IV aGVHD-free probability')\n",
    "plt.savefig('fig/kaplan_meier.svg')\n",
    "plt.show()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Clustering results\n",
    "\n",
    "`'Temp-slope', 'Temp-abs(A1)', 'Temp-angle(A1)', 'SBP-abs(A1)'`"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 119,
   "metadata": {},
   "outputs": [],
   "source": [
    "from sklearn import preprocessing\n",
    "from sklearn.cluster import KMeans, SpectralClustering\n",
    "from sklearn.decomposition import PCA"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 86,
   "metadata": {},
   "outputs": [],
   "source": [
    "extracted_features = pd.read_csv('data/ts_features.csv', index_col='id')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 100,
   "metadata": {},
   "outputs": [
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       "      <td>...</td>\n",
       "      <td>1.444653</td>\n",
       "      <td>145.906924</td>\n",
       "      <td>0.045118</td>\n",
       "      <td>35.911111</td>\n",
       "      <td>2.197225</td>\n",
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       "      <td>0.225669</td>\n",
       "      <td>1.727221</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <td>201406005</td>\n",
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       "      <td>2.708050</td>\n",
       "      <td>...</td>\n",
       "      <td>2.181057</td>\n",
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       "      <td>0.030110</td>\n",
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       "      <td>2.014903</td>\n",
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       "  </tbody>\n",
       "</table>\n",
       "<p>5 rows × 120 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "           DiaBP_dt=1_max__fft_coefficient__coeff_1__attr_\"abs\"  \\\n",
       "id                                                                \n",
       "201406001                                          13.711126      \n",
       "201406002                                           3.452240      \n",
       "201406003                                          14.437545      \n",
       "201406004                                          39.672864      \n",
       "201406005                                          46.236218      \n",
       "\n",
       "           DiaBP_dt=1_max__fft_coefficient__coeff_1__attr_\"angle\"  \\\n",
       "id                                                                  \n",
       "201406001                                         -39.840250        \n",
       "201406002                                          42.925589        \n",
       "201406003                                         161.710499        \n",
       "201406004                                         -56.532935        \n",
       "201406005                                         -83.519009        \n",
       "\n",
       "           DiaBP_dt=1_max__linear_trend__attr_\"slope\"  DiaBP_dt=1_max__mean  \\\n",
       "id                                                                            \n",
       "201406001                                   -1.151515                  80.8   \n",
       "201406002                                   -0.066667                  77.5   \n",
       "201406003                                   -0.151515                  86.9   \n",
       "201406004                                   -0.939394                  78.7   \n",
       "201406005                                   -2.454545                  77.7   \n",
       "\n",
       "           DiaBP_dt=1_max__sample_entropy  \\\n",
       "id                                          \n",
       "201406001                        1.504077   \n",
       "201406002                        2.420368   \n",
       "201406003                        2.708050   \n",
       "201406004                        2.014903   \n",
       "201406005                        2.014903   \n",
       "\n",
       "           DiaBP_dt=1_mean__fft_coefficient__coeff_1__attr_\"abs\"  \\\n",
       "id                                                                 \n",
       "201406001                                          12.511950       \n",
       "201406002                                          17.946614       \n",
       "201406003                                          18.338949       \n",
       "201406004                                          21.591328       \n",
       "201406005                                          45.041080       \n",
       "\n",
       "           DiaBP_dt=1_mean__fft_coefficient__coeff_1__attr_\"angle\"  \\\n",
       "id                                                                   \n",
       "201406001                                         -60.302991         \n",
       "201406002                                         -14.951144         \n",
       "201406003                                        -169.211341         \n",
       "201406004                                         -62.275730         \n",
       "201406005                                        -100.861026         \n",
       "\n",
       "           DiaBP_dt=1_mean__linear_trend__attr_\"slope\"  DiaBP_dt=1_mean__mean  \\\n",
       "id                                                                              \n",
       "201406001                                    -0.771727              70.326825   \n",
       "201406002                                    -0.530707              69.379524   \n",
       "201406003                                     0.150459              76.578379   \n",
       "201406004                                    -0.655020              67.781822   \n",
       "201406005                                    -1.821655              69.535720   \n",
       "\n",
       "           DiaBP_dt=1_mean__sample_entropy  ...  \\\n",
       "id                                          ...   \n",
       "201406001                         2.420368  ...   \n",
       "201406002                         2.014903  ...   \n",
       "201406003                         1.860752  ...   \n",
       "201406004                         1.504077  ...   \n",
       "201406005                         2.708050  ...   \n",
       "\n",
       "           Temp_dt=1_min__fft_coefficient__coeff_1__attr_\"abs\"  \\\n",
       "id                                                               \n",
       "201406001                                           0.567878     \n",
       "201406002                                           0.164019     \n",
       "201406003                                           0.501112     \n",
       "201406004                                           1.444653     \n",
       "201406005                                           2.181057     \n",
       "\n",
       "           Temp_dt=1_min__fft_coefficient__coeff_1__attr_\"angle\"  \\\n",
       "id                                                                 \n",
       "201406001                                          73.555730       \n",
       "201406002                                         -59.464582       \n",
       "201406003                                         -73.426276       \n",
       "201406004                                         145.906924       \n",
       "201406005                                          78.501122       \n",
       "\n",
       "           Temp_dt=1_min__linear_trend__attr_\"slope\"  Temp_dt=1_min__mean  \\\n",
       "id                                                                          \n",
       "201406001                                   0.021481            36.518889   \n",
       "201406002                                   0.009091            36.316667   \n",
       "201406003                                  -0.042088            36.172222   \n",
       "201406004                                   0.045118            35.911111   \n",
       "201406005                                   0.113805            36.288889   \n",
       "\n",
       "           Temp_dt=1_min__sample_entropy  \\\n",
       "id                                         \n",
       "201406001                       1.860752   \n",
       "201406002                       2.420368   \n",
       "201406003                       2.420368   \n",
       "201406004                       2.197225   \n",
       "201406005                       2.420368   \n",
       "\n",
       "           Temp_dt=1_std__fft_coefficient__coeff_1__attr_\"abs\"  \\\n",
       "id                                                               \n",
       "201406001                                           0.263259     \n",
       "201406002                                           0.265981     \n",
       "201406003                                           0.431178     \n",
       "201406004                                           0.420941     \n",
       "201406005                                           0.512131     \n",
       "\n",
       "           Temp_dt=1_std__fft_coefficient__coeff_1__attr_\"angle\"  \\\n",
       "id                                                                 \n",
       "201406001                                          69.530757       \n",
       "201406002                                         100.908363       \n",
       "201406003                                        -149.344978       \n",
       "201406004                                          -3.505990       \n",
       "201406005                                         118.454862       \n",
       "\n",
       "           Temp_dt=1_std__linear_trend__attr_\"slope\"  Temp_dt=1_std__mean  \\\n",
       "id                                                                          \n",
       "201406001                                   0.018092             0.220617   \n",
       "201406002                                   0.004882             0.268865   \n",
       "201406003                                  -0.000899             0.284152   \n",
       "201406004                                  -0.006831             0.225669   \n",
       "201406005                                   0.030110             0.271239   \n",
       "\n",
       "           Temp_dt=1_std__sample_entropy  \n",
       "id                                        \n",
       "201406001                       2.420368  \n",
       "201406002                       2.708050  \n",
       "201406003                       2.197225  \n",
       "201406004                       1.727221  \n",
       "201406005                       2.014903  \n",
       "\n",
       "[5 rows x 120 columns]"
      ]
     },
     "execution_count": 100,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "extracted_features.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 89,
   "metadata": {},
   "outputs": [],
   "source": [
    "cols = [\n",
    "    c for c in extracted_features.columns\n",
    "    if c.startswith('Temp') or c.startswith('SysBP')\n",
    "]\n",
    "cols = [\n",
    "    c for c in cols\n",
    "    if \\\n",
    "    ('Temp' in c and 'slope' in c) or \\\n",
    "    ('Temp' in c and 'fft_coefficient__coeff_1__attr_\"abs\"' in c) or \\\n",
    "    ('Temp' in c and 'fft_coefficient__coeff_1__attr_\"angle\"' in c) or \\\n",
    "    ('SysBP' in c and 'fft_coefficient__coeff_1__attr_\"abs\"' in c)\n",
    "]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 96,
   "metadata": {},
   "outputs": [],
   "source": [
    "XX = extracted_features[cols].values\n",
    "scaler = preprocessing.StandardScaler()\n",
    "XX = scaler.fit_transform(XX)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 97,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(324, 16)"
      ]
     },
     "execution_count": 97,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "XX.shape"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 104,
   "metadata": {},
   "outputs": [],
   "source": [
    "pca = PCA(2, random_state=0).fit(XX)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 176,
   "metadata": {},
   "outputs": [],
   "source": [
    "clusterings = [np.nan, np.nan]\n",
    "scores = [np.nan, np.nan]\n",
    "for k in range(2,11):\n",
    "    cluster = KMeans(k, random_state=0, n_init=20, n_jobs=-1).fit(XX)\n",
    "    clusterings.append(cluster)\n",
    "    scores.append(cluster.inertia_)\n",
    "#     purities, sizes = [], []\n",
    "#     for c in range(k):\n",
    "#         m = (cluster.labels_ == c)\n",
    "#         yc = y[m].mean()\n",
    "#         purities.append(max(yc, 1-yc))\n",
    "#         sizes.append(sum(m) / len(y))\n",
    "#     purity = np.array(purities) @ np.array(sizes)\n",
    "#     scores.append(purity)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "plt.plot(scores)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 220,
   "metadata": {},
   "outputs": [],
   "source": [
    "k = 3\n",
    "cluster = clusterings[k]\n",
    "pred = cluster.fit_predict(XX)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 221,
   "metadata": {},
   "outputs": [],
   "source": [
    "purities, majority = [], []\n",
    "for c in range(k):\n",
    "    m = (cluster.labels_ == c)\n",
    "    yc = y[m].mean()\n",
    "    purities.append(max(yc, 1-yc))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 363,
   "metadata": {},
   "outputs": [
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      ],
      "text/plain": [
       "<Figure size 432x288 with 1 Axes>"
      ]
     },
     "metadata": {
      "needs_background": "light"
     },
     "output_type": "display_data"
    }
   ],
   "source": [
    "# plt.scatter(*pca.transform(XX).T, c=y, s=5, cmap='bwr')\n",
    "X_pca = pca.transform(XX)\n",
    "for i in range(k):\n",
    "    plt.scatter(*X_pca[pred == i].T, c=[plt.get_cmap(\"tab10\")(i)], s=5, \n",
    "                label='Cluster {}, negative cases: {:.1%}'.format(i+1, purities[i]))\n",
    "\n",
    "# plt.scatter(*X_pca.T, c=[plt.get_cmap(\"tab10\")(ci) for ci in pred], s=5)\n",
    "\n",
    "# Mark negative cases with lighter color\n",
    "plt.scatter(*X_pca.T, c=[{0: '#ffffff88', 1: '#00000000'}[yi] for yi in y], s=5)\n",
    "\n",
    "plt.xlabel('First principle component')\n",
    "plt.ylabel('Second principle component')\n",
    "plt.legend(fontsize=8)\n",
    "plt.axis('square')\n",
    "plt.savefig('fig/cluster.svg', bbox_inches='tight')\n",
    "plt.show()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Visualize time series"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [],
   "source": [
    "Xtr, Xte = X[:split_idx], X[split_idx:]\n",
    "ytr, yte = y[:split_idx], y[split_idx:]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [],
   "source": [
    "import pickle\n",
    "ts_vitals_by_bmt = pickle.load(open(data_dir + 'features/ts_vitals_by_bmt_2014_2017_MiChart.p', 'rb'))\n",
    "ts_vitals_by_bmt = {ID: ts_vitals_by_bmt[ID] for ID in list(pop.index)}\n",
    "split_idx = len(ts_vitals_by_bmt)-85\n",
    "\n",
    "clf = load('data/model_combined.joblib')\n",
    "y_prob = clf.predict_proba(Xte)[:,1]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [],
   "source": [
    "imax, imin = y_prob.argmax(), y_prob.argmin()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [],
   "source": [
    "ID_max = pop.index[split_idx+imax]\n",
    "ts_imax = ts_vitals_by_bmt[ID_max]\n",
    "ID_min = pop.index[split_idx+imin]\n",
    "ts_imin = ts_vitals_by_bmt[ID_min]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(201708006, 201711007)"
      ]
     },
     "execution_count": 16,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "ID_max, ID_min"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 41,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(0.21920581756972551, 0.7284919042899778)"
      ]
     },
     "execution_count": 41,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "y_prob[imin], y_prob[imax]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 46,
   "metadata": {},
   "outputs": [
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      "text/plain": [
       "<Figure size 576x576 with 4 Axes>"
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     },
     "metadata": {
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   ],
   "source": [
    "fig, axes = plt.subplots(2, 2, figsize=(8,8), sharex=True, gridspec_kw={'hspace': 0.1, 'wspace': 0.1})\n",
    "\n",
    "plt.sca(axes[0,0])\n",
    "ts_plot = ts_imax[(ts_imax['t'] >= -10) & (ts_imax['t'] < 15)][['t', 'Temp']].dropna()\n",
    "ts_plot = ts_plot.set_index('t')\n",
    "ts_plot['Temp_MA'] = np.nan\n",
    "wsize = 0.1\n",
    "for t in ts_plot.index:\n",
    "    ts_plot.loc[t, 'Temp_MA'] = np.mean(ts_plot.loc[\n",
    "        (t-wsize < ts_plot.index) & (ts_plot.index < t+wsize), 'Temp'\n",
    "    ])\n",
    "ts_plot = ts_plot.reset_index()\n",
    "x = ts_plot['t']\n",
    "y = ts_plot['Temp_MA']\n",
    "x_new = np.linspace(x.min(), x.max(), 1000)\n",
    "f = interp1d(x, y, kind='quadratic')\n",
    "y_smooth = f(x_new)\n",
    "plt.plot(x_new, y_smooth, '--', lw=0.75, label='   positive example\\npredicted risk: {:.3f}'.format(y_prob[imax]))\n",
    "# plt.plot(ts_plot['t'], ts_plot['Temp_MA'], '-', lw=1, label='positive example')\n",
    "plt.scatter(ts_plot['t'], ts_plot['Temp_MA'], s=5)\n",
    "\n",
    "plt.xlim(-10, 15)\n",
    "plt.ylim(36, 39)\n",
    "# plt.xlabel('Days relative to transplant')\n",
    "plt.ylabel('Temperature (Celsius)')\n",
    "plt.legend()\n",
    "\n",
    "plt.sca(axes[0,1])\n",
    "ts_plot = ts_imin[(ts_imin['t'] >= -10) & (ts_imin['t'] < 15)][['t', 'Temp']].dropna()\n",
    "ts_plot = ts_plot.set_index('t')\n",
    "ts_plot['Temp_MA'] = np.nan\n",
    "wsize = 0.1\n",
    "for t in ts_plot.index:\n",
    "    ts_plot.loc[t, 'Temp_MA'] = np.mean(ts_plot.loc[\n",
    "        (t-wsize < ts_plot.index) & (ts_plot.index < t+wsize), 'Temp'\n",
    "    ])\n",
    "ts_plot = ts_plot.reset_index()\n",
    "x = ts_plot['t']\n",
    "y = ts_plot['Temp_MA']\n",
    "x_new = np.linspace(x.min(), x.max(), 1000)\n",
    "f = interp1d(x, y, kind='quadratic')\n",
    "y_smooth = f(x_new)\n",
    "plt.plot(x_new, y_smooth, '--', lw=0.75, label='  negative example\\npredicted risk: {:.3f}'.format(y_prob[imin]), c='tab:orange')\n",
    "# plt.plot(ts_plot['t'], ts_plot['Temp_MA'], '-', lw=1, label='negative example')\n",
    "plt.scatter(ts_plot['t'], ts_plot['Temp_MA'], s=5, c='tab:orange')\n",
    "\n",
    "plt.xlim(-10, 15)\n",
    "plt.ylim(36, 39)\n",
    "# plt.xlabel('Days relative to transplant')\n",
    "# plt.ylabel('Temperature (Celsius)')\n",
    "plt.legend()\n",
    "\n",
    "plt.sca(axes[1,0])\n",
    "ts_plot = ts_imax[(ts_imax['t'] >= -10) & (ts_imax['t'] < 15)][['t', 'SysBP']].dropna()\n",
    "ts_plot = ts_plot.set_index('t')\n",
    "ts_plot['SysBP_MA'] = np.nan\n",
    "wsize = 0.1\n",
    "for t in ts_plot.index:\n",
    "    ts_plot.loc[t, 'SysBP_MA'] = np.mean(ts_plot.loc[\n",
    "        (t-wsize < ts_plot.index) & (ts_plot.index < t+wsize), 'SysBP'\n",
    "    ])\n",
    "ts_plot = ts_plot.reset_index()\n",
    "ts_plot = ts_plot.sort_values(by=['t'])\n",
    "ts_plot = ts_plot.drop_duplicates(subset=['t'])\n",
    "x = ts_plot['t']\n",
    "y = ts_plot['SysBP_MA']\n",
    "x_new = np.linspace(x.min(), x.max(), 1000)\n",
    "f = interp1d(x, y, kind='quadratic')\n",
    "y_smooth = f(x_new)\n",
    "plt.plot(x_new, y_smooth, '--', lw=0.75, label='positive example')\n",
    "plt.scatter(ts_plot['t'], ts_plot['SysBP_MA'], s=5)\n",
    "\n",
    "plt.xlim(-10, 15)\n",
    "# plt.ylim(85, 101)\n",
    "plt.xlabel('Days relative to transplant')\n",
    "plt.ylabel('SysBP (mmHg)')\n",
    "# plt.legend()\n",
    "\n",
    "plt.sca(axes[1,1])\n",
    "ts_plot = ts_imin[(ts_imin['t'] >= -10) & (ts_imin['t'] < 15)][['t', 'SysBP']].dropna()\n",
    "ts_plot = ts_plot.set_index('t')\n",
    "ts_plot['SysBP_MA'] = np.nan\n",
    "wsize = 0.1\n",
    "for t in ts_plot.index:\n",
    "    ts_plot.loc[t, 'SysBP_MA'] = np.mean(ts_plot.loc[\n",
    "        (t-wsize < ts_plot.index) & (ts_plot.index < t+wsize), 'SysBP'\n",
    "    ])\n",
    "ts_plot = ts_plot.reset_index()\n",
    "ts_plot = ts_plot.sort_values(by=['t'])\n",
    "ts_plot = ts_plot.drop_duplicates(subset=['t'])\n",
    "x = ts_plot['t']\n",
    "y = ts_plot['SysBP_MA']\n",
    "x_new = np.linspace(x.min(), x.max(), 1000)\n",
    "f = interp1d(x, y, kind='quadratic')\n",
    "y_smooth = f(x_new)\n",
    "plt.plot(x_new, y_smooth, '--', lw=0.75, label='negative example', c='tab:orange')\n",
    "plt.scatter(ts_plot['t'], ts_plot['SysBP_MA'], s=5, c='tab:orange')\n",
    "\n",
    "plt.xlim(-10, 15)\n",
    "# plt.ylim(85, 101)\n",
    "plt.xlabel('Days relative to transplant')\n",
    "# plt.ylabel('SysBP (mmHg)')\n",
    "# plt.legend()\n",
    "\n",
    "for ax in axes.flat:\n",
    "    ax.label_outer()\n",
    "\n",
    "plt.savefig('fig/timeseries_Temp_SBP.svg')\n",
    "plt.show()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
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