Tractor-Example-GWAS.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Initialize Hail"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "Running on Apache Spark version 2.4.4\n",
      "SparkUI available at http://ega-m.c.ukbb-diversepops-neale.internal:4040\n",
      "Welcome to\n",
      "     __  __     <>__\n",
      "    / /_/ /__  __/ /\n",
      "   / __  / _ `/ / /\n",
      "  /_/ /_/\\_,_/_/_/   version 0.2.32-a5876a0a2853\n",
      "LOGGING: writing to /home/hail/hail-20200210-1851-0.2.32-a5876a0a2853.log\n"
     ]
    }
   ],
   "source": [
    "import argparse\n",
    "import hail as hl\n",
    "import numpy as np\n",
    "hl.init()\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "\n",
       "    <div class=\"bk-root\">\n",
       "        <a href=\"https://bokeh.pydata.org\" target=\"_blank\" class=\"bk-logo bk-logo-small bk-logo-notebook\"></a>\n",
       "        <span id=\"1001\">Loading BokehJS ...</span>\n",
       "    </div>"
      ]
     },
     "metadata": {},
     "output_type": "display_data"
    },
    {
     "data": {
      "application/javascript": [
       "\n",
       "(function(root) {\n",
       "  function now() {\n",
       "    return new Date();\n",
       "  }\n",
       "\n",
       "  var force = true;\n",
       "\n",
       "  if (typeof root._bokeh_onload_callbacks === \"undefined\" || force === true) {\n",
       "    root._bokeh_onload_callbacks = [];\n",
       "    root._bokeh_is_loading = undefined;\n",
       "  }\n",
       "\n",
       "  var JS_MIME_TYPE = 'application/javascript';\n",
       "  var HTML_MIME_TYPE = 'text/html';\n",
       "  var EXEC_MIME_TYPE = 'application/vnd.bokehjs_exec.v0+json';\n",
       "  var CLASS_NAME = 'output_bokeh rendered_html';\n",
       "\n",
       "  /**\n",
       "   * Render data to the DOM node\n",
       "   */\n",
       "  function render(props, node) {\n",
       "    var script = document.createElement(\"script\");\n",
       "    node.appendChild(script);\n",
       "  }\n",
       "\n",
       "  /**\n",
       "   * Handle when an output is cleared or removed\n",
       "   */\n",
       "  function handleClearOutput(event, handle) {\n",
       "    var cell = handle.cell;\n",
       "\n",
       "    var id = cell.output_area._bokeh_element_id;\n",
       "    var server_id = cell.output_area._bokeh_server_id;\n",
       "    // Clean up Bokeh references\n",
       "    if (id != null && id in Bokeh.index) {\n",
       "      Bokeh.index[id].model.document.clear();\n",
       "      delete Bokeh.index[id];\n",
       "    }\n",
       "\n",
       "    if (server_id !== undefined) {\n",
       "      // Clean up Bokeh references\n",
       "      var cmd = \"from bokeh.io.state import curstate; print(curstate().uuid_to_server['\" + server_id + \"'].get_sessions()[0].document.roots[0]._id)\";\n",
       "      cell.notebook.kernel.execute(cmd, {\n",
       "        iopub: {\n",
       "          output: function(msg) {\n",
       "            var id = msg.content.text.trim();\n",
       "            if (id in Bokeh.index) {\n",
       "              Bokeh.index[id].model.document.clear();\n",
       "              delete Bokeh.index[id];\n",
       "            }\n",
       "          }\n",
       "        }\n",
       "      });\n",
       "      // Destroy server and session\n",
       "      var cmd = \"import bokeh.io.notebook as ion; ion.destroy_server('\" + server_id + \"')\";\n",
       "      cell.notebook.kernel.execute(cmd);\n",
       "    }\n",
       "  }\n",
       "\n",
       "  /**\n",
       "   * Handle when a new output is added\n",
       "   */\n",
       "  function handleAddOutput(event, handle) {\n",
       "    var output_area = handle.output_area;\n",
       "    var output = handle.output;\n",
       "\n",
       "    // limit handleAddOutput to display_data with EXEC_MIME_TYPE content only\n",
       "    if ((output.output_type != \"display_data\") || (!output.data.hasOwnProperty(EXEC_MIME_TYPE))) {\n",
       "      return\n",
       "    }\n",
       "\n",
       "    var toinsert = output_area.element.find(\".\" + CLASS_NAME.split(' ')[0]);\n",
       "\n",
       "    if (output.metadata[EXEC_MIME_TYPE][\"id\"] !== undefined) {\n",
       "      toinsert[toinsert.length - 1].firstChild.textContent = output.data[JS_MIME_TYPE];\n",
       "      // store reference to embed id on output_area\n",
       "      output_area._bokeh_element_id = output.metadata[EXEC_MIME_TYPE][\"id\"];\n",
       "    }\n",
       "    if (output.metadata[EXEC_MIME_TYPE][\"server_id\"] !== undefined) {\n",
       "      var bk_div = document.createElement(\"div\");\n",
       "      bk_div.innerHTML = output.data[HTML_MIME_TYPE];\n",
       "      var script_attrs = bk_div.children[0].attributes;\n",
       "      for (var i = 0; i < script_attrs.length; i++) {\n",
       "        toinsert[toinsert.length - 1].firstChild.setAttribute(script_attrs[i].name, script_attrs[i].value);\n",
       "      }\n",
       "      // store reference to server id on output_area\n",
       "      output_area._bokeh_server_id = output.metadata[EXEC_MIME_TYPE][\"server_id\"];\n",
       "    }\n",
       "  }\n",
       "\n",
       "  function register_renderer(events, OutputArea) {\n",
       "\n",
       "    function append_mime(data, metadata, element) {\n",
       "      // create a DOM node to render to\n",
       "      var toinsert = this.create_output_subarea(\n",
       "        metadata,\n",
       "        CLASS_NAME,\n",
       "        EXEC_MIME_TYPE\n",
       "      );\n",
       "      this.keyboard_manager.register_events(toinsert);\n",
       "      // Render to node\n",
       "      var props = {data: data, metadata: metadata[EXEC_MIME_TYPE]};\n",
       "      render(props, toinsert[toinsert.length - 1]);\n",
       "      element.append(toinsert);\n",
       "      return toinsert\n",
       "    }\n",
       "\n",
       "    /* Handle when an output is cleared or removed */\n",
       "    events.on('clear_output.CodeCell', handleClearOutput);\n",
       "    events.on('delete.Cell', handleClearOutput);\n",
       "\n",
       "    /* Handle when a new output is added */\n",
       "    events.on('output_added.OutputArea', handleAddOutput);\n",
       "\n",
       "    /**\n",
       "     * Register the mime type and append_mime function with output_area\n",
       "     */\n",
       "    OutputArea.prototype.register_mime_type(EXEC_MIME_TYPE, append_mime, {\n",
       "      /* Is output safe? */\n",
       "      safe: true,\n",
       "      /* Index of renderer in `output_area.display_order` */\n",
       "      index: 0\n",
       "    });\n",
       "  }\n",
       "\n",
       "  // register the mime type if in Jupyter Notebook environment and previously unregistered\n",
       "  if (root.Jupyter !== undefined) {\n",
       "    var events = require('base/js/events');\n",
       "    var OutputArea = require('notebook/js/outputarea').OutputArea;\n",
       "\n",
       "    if (OutputArea.prototype.mime_types().indexOf(EXEC_MIME_TYPE) == -1) {\n",
       "      register_renderer(events, OutputArea);\n",
       "    }\n",
       "  }\n",
       "\n",
       "  \n",
       "  if (typeof (root._bokeh_timeout) === \"undefined\" || force === true) {\n",
       "    root._bokeh_timeout = Date.now() + 5000;\n",
       "    root._bokeh_failed_load = false;\n",
       "  }\n",
       "\n",
       "  var NB_LOAD_WARNING = {'data': {'text/html':\n",
       "     \"<div style='background-color: #fdd'>\\n\"+\n",
       "     \"<p>\\n\"+\n",
       "     \"BokehJS does not appear to have successfully loaded. If loading BokehJS from CDN, this \\n\"+\n",
       "     \"may be due to a slow or bad network connection. Possible fixes:\\n\"+\n",
       "     \"</p>\\n\"+\n",
       "     \"<ul>\\n\"+\n",
       "     \"<li>re-rerun `output_notebook()` to attempt to load from CDN again, or</li>\\n\"+\n",
       "     \"<li>use INLINE resources instead, as so:</li>\\n\"+\n",
       "     \"</ul>\\n\"+\n",
       "     \"<code>\\n\"+\n",
       "     \"from bokeh.resources import INLINE\\n\"+\n",
       "     \"output_notebook(resources=INLINE)\\n\"+\n",
       "     \"</code>\\n\"+\n",
       "     \"</div>\"}};\n",
       "\n",
       "  function display_loaded() {\n",
       "    var el = document.getElementById(\"1001\");\n",
       "    if (el != null) {\n",
       "      el.textContent = \"BokehJS is loading...\";\n",
       "    }\n",
       "    if (root.Bokeh !== undefined) {\n",
       "      if (el != null) {\n",
       "        el.textContent = \"BokehJS \" + root.Bokeh.version + \" successfully loaded.\";\n",
       "      }\n",
       "    } else if (Date.now() < root._bokeh_timeout) {\n",
       "      setTimeout(display_loaded, 100)\n",
       "    }\n",
       "  }\n",
       "\n",
       "\n",
       "  function run_callbacks() {\n",
       "    try {\n",
       "      root._bokeh_onload_callbacks.forEach(function(callback) {\n",
       "        if (callback != null)\n",
       "          callback();\n",
       "      });\n",
       "    } finally {\n",
       "      delete root._bokeh_onload_callbacks\n",
       "    }\n",
       "    console.debug(\"Bokeh: all callbacks have finished\");\n",
       "  }\n",
       "\n",
       "  function load_libs(css_urls, js_urls, callback) {\n",
       "    if (css_urls == null) css_urls = [];\n",
       "    if (js_urls == null) js_urls = [];\n",
       "\n",
       "    root._bokeh_onload_callbacks.push(callback);\n",
       "    if (root._bokeh_is_loading > 0) {\n",
       "      console.debug(\"Bokeh: BokehJS is being loaded, scheduling callback at\", now());\n",
       "      return null;\n",
       "    }\n",
       "    if (js_urls == null || js_urls.length === 0) {\n",
       "      run_callbacks();\n",
       "      return null;\n",
       "    }\n",
       "    console.debug(\"Bokeh: BokehJS not loaded, scheduling load and callback at\", now());\n",
       "    root._bokeh_is_loading = css_urls.length + js_urls.length;\n",
       "\n",
       "    function on_load() {\n",
       "      root._bokeh_is_loading--;\n",
       "      if (root._bokeh_is_loading === 0) {\n",
       "        console.debug(\"Bokeh: all BokehJS libraries/stylesheets loaded\");\n",
       "        run_callbacks()\n",
       "      }\n",
       "    }\n",
       "\n",
       "    function on_error() {\n",
       "      console.error(\"failed to load \" + url);\n",
       "    }\n",
       "\n",
       "    for (var i = 0; i < css_urls.length; i++) {\n",
       "      var url = css_urls[i];\n",
       "      const element = document.createElement(\"link\");\n",
       "      element.onload = on_load;\n",
       "      element.onerror = on_error;\n",
       "      element.rel = \"stylesheet\";\n",
       "      element.type = \"text/css\";\n",
       "      element.href = url;\n",
       "      console.debug(\"Bokeh: injecting link tag for BokehJS stylesheet: \", url);\n",
       "      document.body.appendChild(element);\n",
       "    }\n",
       "\n",
       "    for (var i = 0; i < js_urls.length; i++) {\n",
       "      var url = js_urls[i];\n",
       "      var element = document.createElement('script');\n",
       "      element.onload = on_load;\n",
       "      element.onerror = on_error;\n",
       "      element.async = false;\n",
       "      element.src = url;\n",
       "      console.debug(\"Bokeh: injecting script tag for BokehJS library: \", url);\n",
       "      document.head.appendChild(element);\n",
       "    }\n",
       "  };var element = document.getElementById(\"1001\");\n",
       "  if (element == null) {\n",
       "    console.error(\"Bokeh: ERROR: autoload.js configured with elementid '1001' but no matching script tag was found. \")\n",
       "    return false;\n",
       "  }\n",
       "\n",
       "  function inject_raw_css(css) {\n",
       "    const element = document.createElement(\"style\");\n",
       "    element.appendChild(document.createTextNode(css));\n",
       "    document.body.appendChild(element);\n",
       "  }\n",
       "\n",
       "  var js_urls = [\"https://cdn.pydata.org/bokeh/release/bokeh-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-widgets-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-tables-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-gl-1.2.0.min.js\"];\n",
       "  var css_urls = [\"https://cdn.pydata.org/bokeh/release/bokeh-1.2.0.min.css\", \"https://cdn.pydata.org/bokeh/release/bokeh-widgets-1.2.0.min.css\", \"https://cdn.pydata.org/bokeh/release/bokeh-tables-1.2.0.min.css\"];\n",
       "\n",
       "  var inline_js = [\n",
       "    function(Bokeh) {\n",
       "      Bokeh.set_log_level(\"info\");\n",
       "    },\n",
       "    \n",
       "    function(Bokeh) {\n",
       "      \n",
       "    },\n",
       "    function(Bokeh) {} // ensure no trailing comma for IE\n",
       "  ];\n",
       "\n",
       "  function run_inline_js() {\n",
       "    \n",
       "    if ((root.Bokeh !== undefined) || (force === true)) {\n",
       "      for (var i = 0; i < inline_js.length; i++) {\n",
       "        inline_js[i].call(root, root.Bokeh);\n",
       "      }if (force === true) {\n",
       "        display_loaded();\n",
       "      }} else if (Date.now() < root._bokeh_timeout) {\n",
       "      setTimeout(run_inline_js, 100);\n",
       "    } else if (!root._bokeh_failed_load) {\n",
       "      console.log(\"Bokeh: BokehJS failed to load within specified timeout.\");\n",
       "      root._bokeh_failed_load = true;\n",
       "    } else if (force !== true) {\n",
       "      var cell = $(document.getElementById(\"1001\")).parents('.cell').data().cell;\n",
       "      cell.output_area.append_execute_result(NB_LOAD_WARNING)\n",
       "    }\n",
       "\n",
       "  }\n",
       "\n",
       "  if (root._bokeh_is_loading === 0) {\n",
       "    console.debug(\"Bokeh: BokehJS loaded, going straight to plotting\");\n",
       "    run_inline_js();\n",
       "  } else {\n",
       "    load_libs(css_urls, js_urls, function() {\n",
       "      console.debug(\"Bokeh: BokehJS plotting callback run at\", now());\n",
       "      run_inline_js();\n",
       "    });\n",
       "  }\n",
       "}(window));"
      ],
      "application/vnd.bokehjs_load.v0+json": "\n(function(root) {\n  function now() {\n    return new Date();\n  }\n\n  var force = true;\n\n  if (typeof root._bokeh_onload_callbacks === \"undefined\" || force === true) {\n    root._bokeh_onload_callbacks = [];\n    root._bokeh_is_loading = undefined;\n  }\n\n  \n\n  \n  if (typeof (root._bokeh_timeout) === \"undefined\" || force === true) {\n    root._bokeh_timeout = Date.now() + 5000;\n    root._bokeh_failed_load = false;\n  }\n\n  var NB_LOAD_WARNING = {'data': {'text/html':\n     \"<div style='background-color: #fdd'>\\n\"+\n     \"<p>\\n\"+\n     \"BokehJS does not appear to have successfully loaded. If loading BokehJS from CDN, this \\n\"+\n     \"may be due to a slow or bad network connection. Possible fixes:\\n\"+\n     \"</p>\\n\"+\n     \"<ul>\\n\"+\n     \"<li>re-rerun `output_notebook()` to attempt to load from CDN again, or</li>\\n\"+\n     \"<li>use INLINE resources instead, as so:</li>\\n\"+\n     \"</ul>\\n\"+\n     \"<code>\\n\"+\n     \"from bokeh.resources import INLINE\\n\"+\n     \"output_notebook(resources=INLINE)\\n\"+\n     \"</code>\\n\"+\n     \"</div>\"}};\n\n  function display_loaded() {\n    var el = document.getElementById(\"1001\");\n    if (el != null) {\n      el.textContent = \"BokehJS is loading...\";\n    }\n    if (root.Bokeh !== undefined) {\n      if (el != null) {\n        el.textContent = \"BokehJS \" + root.Bokeh.version + \" successfully loaded.\";\n      }\n    } else if (Date.now() < root._bokeh_timeout) {\n      setTimeout(display_loaded, 100)\n    }\n  }\n\n\n  function run_callbacks() {\n    try {\n      root._bokeh_onload_callbacks.forEach(function(callback) {\n        if (callback != null)\n          callback();\n      });\n    } finally {\n      delete root._bokeh_onload_callbacks\n    }\n    console.debug(\"Bokeh: all callbacks have finished\");\n  }\n\n  function load_libs(css_urls, js_urls, callback) {\n    if (css_urls == null) css_urls = [];\n    if (js_urls == null) js_urls = [];\n\n    root._bokeh_onload_callbacks.push(callback);\n    if (root._bokeh_is_loading > 0) {\n      console.debug(\"Bokeh: BokehJS is being loaded, scheduling callback at\", now());\n      return null;\n    }\n    if (js_urls == null || js_urls.length === 0) {\n      run_callbacks();\n      return null;\n    }\n    console.debug(\"Bokeh: BokehJS not loaded, scheduling load and callback at\", now());\n    root._bokeh_is_loading = css_urls.length + js_urls.length;\n\n    function on_load() {\n      root._bokeh_is_loading--;\n      if (root._bokeh_is_loading === 0) {\n        console.debug(\"Bokeh: all BokehJS libraries/stylesheets loaded\");\n        run_callbacks()\n      }\n    }\n\n    function on_error() {\n      console.error(\"failed to load \" + url);\n    }\n\n    for (var i = 0; i < css_urls.length; i++) {\n      var url = css_urls[i];\n      const element = document.createElement(\"link\");\n      element.onload = on_load;\n      element.onerror = on_error;\n      element.rel = \"stylesheet\";\n      element.type = \"text/css\";\n      element.href = url;\n      console.debug(\"Bokeh: injecting link tag for BokehJS stylesheet: \", url);\n      document.body.appendChild(element);\n    }\n\n    for (var i = 0; i < js_urls.length; i++) {\n      var url = js_urls[i];\n      var element = document.createElement('script');\n      element.onload = on_load;\n      element.onerror = on_error;\n      element.async = false;\n      element.src = url;\n      console.debug(\"Bokeh: injecting script tag for BokehJS library: \", url);\n      document.head.appendChild(element);\n    }\n  };var element = document.getElementById(\"1001\");\n  if (element == null) {\n    console.error(\"Bokeh: ERROR: autoload.js configured with elementid '1001' but no matching script tag was found. \")\n    return false;\n  }\n\n  function inject_raw_css(css) {\n    const element = document.createElement(\"style\");\n    element.appendChild(document.createTextNode(css));\n    document.body.appendChild(element);\n  }\n\n  var js_urls = [\"https://cdn.pydata.org/bokeh/release/bokeh-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-widgets-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-tables-1.2.0.min.js\", \"https://cdn.pydata.org/bokeh/release/bokeh-gl-1.2.0.min.js\"];\n  var css_urls = [\"https://cdn.pydata.org/bokeh/release/bokeh-1.2.0.min.css\", \"https://cdn.pydata.org/bokeh/release/bokeh-widgets-1.2.0.min.css\", \"https://cdn.pydata.org/bokeh/release/bokeh-tables-1.2.0.min.css\"];\n\n  var inline_js = [\n    function(Bokeh) {\n      Bokeh.set_log_level(\"info\");\n    },\n    \n    function(Bokeh) {\n      \n    },\n    function(Bokeh) {} // ensure no trailing comma for IE\n  ];\n\n  function run_inline_js() {\n    \n    if ((root.Bokeh !== undefined) || (force === true)) {\n      for (var i = 0; i < inline_js.length; i++) {\n        inline_js[i].call(root, root.Bokeh);\n      }if (force === true) {\n        display_loaded();\n      }} else if (Date.now() < root._bokeh_timeout) {\n      setTimeout(run_inline_js, 100);\n    } else if (!root._bokeh_failed_load) {\n      console.log(\"Bokeh: BokehJS failed to load within specified timeout.\");\n      root._bokeh_failed_load = true;\n    } else if (force !== true) {\n      var cell = $(document.getElementById(\"1001\")).parents('.cell').data().cell;\n      cell.output_area.append_execute_result(NB_LOAD_WARNING)\n    }\n\n  }\n\n  if (root._bokeh_is_loading === 0) {\n    console.debug(\"Bokeh: BokehJS loaded, going straight to plotting\");\n    run_inline_js();\n  } else {\n    load_libs(css_urls, js_urls, function() {\n      console.debug(\"Bokeh: BokehJS plotting callback run at\", now());\n      run_inline_js();\n    });\n  }\n}(window));"
     },
     "metadata": {},
     "output_type": "display_data"
    }
   ],
   "source": [
    "#load in plotting features\n",
    "from hail.plot import show\n",
    "from pprint import pprint\n",
    "hl.plot.output_notebook()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Load in the filtered and phenotype annotated genotype data for the individuals\n",
    "### Note: the example file is in Matrix Table format, the native Hail format. VCF formats may also be imported with 'hl.import_vcf'. See documentation for more details: https://hail.is/"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#key columns by sample and rows by rsID for easier merge with dosage data\n",
    "mt = hl.read_matrix_table('gs://ukb-diverse-pops/AdmixedAfrEur/Results/UKBB_AfEur_QCed_lipids2.mt').key_rows_by('locus')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Load in the dosage files from Tractor\n",
    "### Note: this will be the most time intensive step. Hail team is actively optimizing pieces of this infrastructure."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "row_fields={'CHROM': hl.tstr, 'POS': hl.tint, 'ID': hl.tstr, 'REF': hl.tstr, 'ALT': hl.tstr} \n",
    "anc0dos = hl.import_matrix_table('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids.autosomes.anc0.dosage_v1.txt.gz', \n",
    "                                 force_bgz=True, row_fields=row_fields, row_key=[], min_partitions=32) \n",
    "anc0dos = anc0dos.key_rows_by().drop('row_id')\n",
    "anc0dos = anc0dos.key_rows_by(locus=hl.locus(anc0dos.CHROM, anc0dos.POS))     "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "row_fields={'CHROM': hl.tstr, 'POS': hl.tint, 'ID': hl.tstr, 'REF': hl.tstr, 'ALT': hl.tstr} \n",
    "anc1dos = hl.import_matrix_table('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids.autosomes.anc1.dosage_v1.txt.gz', \n",
    "                                 force_bgz=True, row_fields=row_fields, row_key=[], min_partitions=32) \n",
    "anc1dos = anc1dos.key_rows_by().drop('row_id')\n",
    "anc1dos = anc1dos.key_rows_by(locus=hl.locus(anc1dos.CHROM, anc1dos.POS))     "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#Optional - save these temporary files to relieve  memory burden\n",
    "anc1dos = anc1dos.checkpoint('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids.autosomes.anc1.dosage_v1.mt')\n",
    "anc0dos = anc0dos.checkpoint('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids.autosomes.anc0.dosage_v1.mt')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#read in haplotype counts for anc0, here African, the index ancestry\n",
    "row_fields={'CHROM': hl.tstr, 'POS': hl.tint, 'ID': hl.tstr} \n",
    "hapcounts0 = hl.import_matrix_table('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids.auto.anc0.hapcount.txt.gz', \n",
    "                                 force_bgz=True, row_fields=row_fields, row_key=[], min_partitions=32) \n",
    "hapcounts0 = hapcounts0.key_rows_by().drop('row_id')\n",
    "hapcounts0 = hapcounts0.key_rows_by(locus=hl.locus(hapcounts0.CHROM, hapcounts0.POS))   "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#join the dosage files to the genotype data. \n",
    "#Specifically, annotating the samples with their info for how many copies of the minor allele per ancestry were seen and index haplotype counts\n",
    "mt = mt.annotate_entries(anc0dos = anc0dos[mt.locus, mt.s], anc1dos = anc1dos[mt.locus, mt.s], hapcounts0 = hapcounts0[mt.locus, mt.s])"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#write out the newly annotated matrix table. Will run a lot faster if we load this in again after annotating things in due to Hail processing style.\n",
    "mt.write('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids_dosages.mt')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Run linear regression across all phenotypes."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "#read in the filtered and annotated mt file again to go faster\n",
    "mt = hl.read_matrix_table('gs://ukb-diverse-pops/AdmixedAfrEur/DosageFiles/UKBB_AfEur_QCed_lipids_dosages.mt')\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "2019-08-23 15:43:21 Hail: WARN: 267 of 4576 samples have a missing phenotype or covariate.\n",
      "2019-08-23 15:43:21 Hail: INFO: linear_regression_rows: running on 4309 samples for 1 response variable y,\n",
      "    with input variable x, and 24 additional covariates...\n"
     ]
    }
   ],
   "source": [
    "#Run GWAS on a single phenotype, here running on TC, Total Cholesterol, using the Tractor haplotype counts and dosages\n",
    "#along with the covariates of ages, sex, blood dilution level, and global ancestry fractions obtained from previous ADMIXTURE runs\n",
    "mt = mt.annotate_rows(TC = hl.agg.linreg(mt.TC,\n",
    "                                                 [1.0, mt.hapcounts0.x, mt.anc0dos.x, mt.anc1dos.x, mt.isMale, mt.age, mt.dilutionFactor, hl.float(mt.admixFrac.AFR)]))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 45,
   "metadata": {},
   "outputs": [],
   "source": [
    "#to run phenotyps in batch, make a list of the phenotype names\n",
    "phenonames = ['TG', 'TC', 'HDLC', 'LDLC']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "2019-08-23 15:43:29 Hail: WARN: 612 of 4576 samples have a missing phenotype or covariate.\n",
      "2019-08-23 15:43:29 Hail: INFO: linear_regression_rows: running on 3964 samples for 1 response variable y,\n",
      "    with input variable x, and 24 additional covariates...\n"
     ]
    }
   ],
   "source": [
    "#run GWAS in batch for all listed phenotypes, annotating with the pheno name\n",
    "mt = mt.annotate_rows(results=hl.struct(**{pheno: hl.agg.linreg(mt[pheno], \n",
    "                                                                [1.0, mt.hapcounts0.x, mt.anc0dos.x, mt.anc1dos.x, mt.isMale, mt.age, mt.dilutionFactor, hl.float(mt.admixFrac.AFR)]) \n",
    "                                           for pheno in phenonames}))\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#plot up as a manhattan plot, anc 0 and anc 1 seperately\n",
    "#in the implementation above, the first p value in the array is for the intercept, the second is ancestry counts at the site, the third is anc0, and the fourth is anc1, followed by the covariates\n",
    "p = hl.plot.manhattan(mt.results.TC.p_value[2], title='Admixed Afr-Eur UKBB, TC, anc0', collect_all=False, significance_line=5e-08) \n",
    "show(p)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#plot up as a manhattan plot, anc 1\n",
    "p = hl.plot.manhattan(mt.results.TC.p_value[3], title='Admixed Afr-Eur UKBB, TC, anc1', collect_all=False, significance_line=5e-08) \n",
    "show(p)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#make a QQ plot for TC anc0\n",
    "p = hl.plot.qq(mt.results.TC.p_value[2], title=\"QQ plot, TC, anc0\")\n",
    "show(p)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#make a QQ plot for TC anc1\n",
    "p = hl.plot.qq(mt.results.TC.p_value[3], title=\"QQ plot, TC, anc1\")\n",
    "show(p)"
   ]
  }
 ],
 "metadata": {
  "kernelspec": {
   "display_name": "Hail",
   "language": "python",
   "name": "hail"
  },
  "language_info": {
   "codemirror_mode": {
    "name": "ipython",
    "version": 3
   },
   "file_extension": ".py",
   "mimetype": "text/x-python",
   "name": "python",
   "nbconvert_exporter": "python",
   "pygments_lexer": "ipython3",
   "version": "3.6.10"
  }
 },
 "nbformat": 4,
 "nbformat_minor": 2
}