{ "cells": [ { "cell_type": "code", "execution_count": 27, "metadata": {}, "outputs": [], "source": [ "import sys\n", "import time\n", "\n", "from pybel.struct import (\n", " get_subgraph_by_induction, expand_upstream_causal, get_upstream_causal_subgraph, has_protein_modification,\n", ")\n", "import hbp_knowledge\n", "from pybel.dsl import Protein\n", "from pybel_jupyter import to_jupyter\n", "from pybel.constants import RELATION, HAS_VARIANT" ] }, { "cell_type": "code", "execution_count": 3, "metadata": {}, "outputs": [ { "data": { "text/plain": [ "'0.0.2'" ] }, "execution_count": 3, "metadata": {}, "output_type": "execute_result" } ], "source": [ "hbp_knowledge.VERSION" ] }, { "cell_type": "code", "execution_count": 4, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "3.7.1 (default, Nov 28 2018, 11:51:47) \n", "[Clang 10.0.0 (clang-1000.11.45.5)]\n" ] } ], "source": [ "print(sys.version)" ] }, { "cell_type": "code", "execution_count": 6, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "Sun Jan 13 19:10:20 2019\n" ] } ], "source": [ "print(time.asctime())" ] }, { "cell_type": "code", "execution_count": 8, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "albuquerque2009 v1.0.0\n", "Number of Nodes: 1934\n", "Number of Edges: 5437\n", "Network Density: 1.45E-03\n", "Number of Components: 18\n", "Number of Warnings: 0\n" ] } ], "source": [ "graph = hbp_knowledge.get_graph()\n", "graph.summarize()" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "List all nodes that have to do with ``tau``." ] }, { "cell_type": "code", "execution_count": 12, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "a(HBP:\"3R tau\")\n", "a(HBP:\"4R tau\")\n", "a(HBP:\"Tau aggregates\")\n", "a(HBP:\"Tau annular protofibrils\")\n", "a(HBP:\"Tau antibody, 40E8\")\n", "a(HBP:\"Tau antibody, 4E4\")\n", "a(HBP:\"Tau antibody, 6C5\")\n", "a(HBP:\"Tau antibody, HT7\")\n", "a(HBP:\"Tau antibody, TNT1\")\n", "a(HBP:\"Tau antibody, Tau-13\")\n", "a(HBP:\"Tau antibody, Tau46\")\n", "a(HBP:\"Tau antibody, pS396\")\n", "a(HBP:\"Tau dimers\")\n", "a(HBP:\"Tau epitope, 12E8\")\n", "a(HBP:\"Tau epitope, AT180\")\n", "a(HBP:\"Tau epitope, AT8\")\n", "a(HBP:\"Tau epitope, PHF1\")\n", "a(HBP:\"Tau fibrils\")\n", "a(HBP:\"Tau isoform B (381 aa)\")\n", "a(HBP:\"Tau isoform C (410 aa)\")\n", "a(HBP:\"Tau isoform D (383 aa)\")\n", "a(HBP:\"Tau isoform E (412 aa)\")\n", "a(HBP:\"Tau isoform F (441 aa)\")\n", "a(HBP:\"Tau isoform Fetal-tau (352 aa)\")\n", "a(HBP:\"Tau oligomers\")\n", "a(HBP:\"granular tau oligomers\")\n", "a(HBP:\"sonicated tau fibrils\")\n", "p(HBP:\"6D tau\", frag(\"2_18\"))\n", "p(HBP:\"6D tau\")\n", "p(HBP:\"Tau isoform F (441 aa)\", var(\"p.Ile277Pro\"), var(\"p.Ile308Pro\"), var(\"p.Lys280del\"))\n", "p(HBP:\"Tau isoform F (441 aa)\")\n", "p(HBP:\"Tau isoform F (441 aa)\", var(\"p.Lys280del\"))\n", "p(HBP:\"6P tau\")\n", "p(HBP:\"AT8 tau\")\n", "p(HBP:\"AT8 tau\", pmod(Ph))\n", "p(HBP:\"Tau aggregates\")\n", "p(HBP:\"Tau fibrils\")\n", "p(HBP:\"Tau isoform B (381 aa)\")\n", "p(HBP:\"Tau isoform B (381 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau isoform C (410 aa)\")\n", "p(HBP:\"Tau isoform C (410 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau isoform D (383 aa)\")\n", "p(HBP:\"Tau isoform D (383 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau isoform E (412 aa)\")\n", "p(HBP:\"Tau isoform E (412 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau isoform F (441 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau isoform Fetal-tau (352 aa)\")\n", "p(HBP:\"Tau isoform Fetal-tau (352 aa)\", pmod(HBP:\"protein aggregation\"))\n", "p(HBP:\"Tau oligomers\")\n", "p(HBP:\"Tau oligomers\", pmod(HBP:hyperphosphorylation))\n", "p(HBP:\"delta 144-273 tau\")\n", "p(HBP:\"tau aggregates\")\n", "path(MESH:Tauopathies)\n", "path(MESHD:Tauopathies)\n" ] } ], "source": [ "nodes = []\n", "for node in graph.nodes():\n", " if 'name' in node and 'tau' in node.name.lower():\n", " print(node)\n", " nodes.append(node)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "Get post-translational modifications of the human Tau protein" ] }, { "cell_type": "code", "execution_count": 39, "metadata": {}, "outputs": [ { "data": { "text/plain": [ "[,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ,\n", " ]" ] }, "execution_count": 39, "metadata": {}, "output_type": "execute_result" } ], "source": [ "mapt = Protein('HGNC', 'MAPT')\n", "nodes = [\n", " v\n", " for u, v, key, data in graph.edges(keys=True, data=True)\n", " if u == mapt and data[RELATION] == HAS_VARIANT and has_protein_modification(v)\n", "]\n", "nodes" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "Induce a subgraph upstream of all PTMs of the human Tau protein." ] }, { "cell_type": "code", "execution_count": 44, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "MAPT Post-Translational Modification Controllers v0.0.2\n", "Number of Nodes: 27\n", "Number of Edges: 26\n", "Network Density: 3.70E-02\n", "Number of Components: 2\n", "Number of Warnings: 0\n" ] }, { "data": { "application/javascript": [ "function init_d3_force(d3, graph, chart, width, height, function_colors) {\n", " var focus_node = null;\n", " var highlight_node = null;\n", "\n", " // Highlight color variables\n", "\n", " // Highlight color of the node boundering\n", " const highlight_node_boundering = \"#4EB2D4\";\n", "\n", " // Highlight color of the edge\n", " const highlighted_link_color = \"#4EB2D4\";\n", "\n", " // Text highlight color\n", " const highlight_text = \"#4EB2D4\";\n", "\n", " // Size when zooming scale\n", " var size = d3.scalePow().exponent(1)\n", " .domain([1, 100])\n", " .range([8, 24]);\n", "\n", " // Simulation parameters\n", " const linkDistance = 100;\n", " const fCharge = -1000;\n", " const linkStrength = 0.7;\n", " const collideStrength = 1;\n", "\n", " // Simulation defined with variables\n", " var simulation = d3.forceSimulation()\n", " .force(\"link\", d3.forceLink()\n", " .distance(linkDistance)\n", " .strength(linkStrength)\n", " )\n", " .force(\"collide\", d3.forceCollide()\n", " .radius(function (d) {\n", " return d.r + 10\n", " })\n", " .strength(collideStrength)\n", " )\n", " .force(\"charge\", d3.forceManyBody()\n", " .strength(fCharge)\n", " )\n", " .force(\"center\", d3.forceCenter(width / 2, height / 2))\n", " .force(\"y\", d3.forceY(0))\n", " .force(\"x\", d3.forceX(0));\n", "\n", " // Pin down functionality\n", " var node_drag = d3.drag()\n", " .on(\"start\", dragstarted)\n", " .on(\"drag\", dragged)\n", " .on(\"end\", dragended);\n", "\n", " function dragstarted(d) {\n", " if (!d3.event.active) simulation.alphaTarget(0.3).restart();\n", " d.fx = d.x;\n", " d.fy = d.y;\n", " }\n", "\n", " function dragged(d) {\n", " d.fx = d3.event.x;\n", " d.fy = d3.event.y;\n", " }\n", "\n", " function dragended(d) {\n", " if (!d3.event.active) simulation.alphaTarget(0);\n", " }\n", "\n", " function releasenode(d) {\n", " d.fx = null;\n", " d.fy = null;\n", " }\n", "\n", " //END Pin down functionality\n", "\n", "\n", " /**\n", " * Gets the best name for a node object\n", " * @param {object} nodeData object\n", " * @returns {str} canonical name of the node\n", " */\n", " function getCanonicalName(nodeData) {\n", " if (nodeData.cname) {\n", " return nodeData.cname;\n", " } else if (nodeData.name) {\n", " return nodeData.name\n", " } else if (nodeData.bel) {\n", " return nodeData.bel\n", " } else {\n", " console.log('Undefined node: ' + nodeData);\n", " return 'UNDEFINED'\n", " }\n", " }\n", "\n", " const color_circunferencia = \"black\";\n", " const default_link_color = \"#AAAAAA\";\n", " const nominal_base_node_size = 8;\n", "\n", " // Normal and highlighted stroke of the links (double the width of the link when highlighted)\n", " const nominal_stroke = 1.5;\n", "\n", " // Zoom variables\n", " const min_zoom = 0.1;\n", " const max_zoom = 10;\n", "\n", " var svg = d3.select(chart).append(\"svg\")\n", " .attr(\"width\", width)\n", " .attr(\"height\", height);\n", "\n", " // // Create definition for arrowhead.\n", " svg.append(\"defs\").append(\"marker\")\n", " .attr(\"id\", \"arrowhead\")\n", " .attr(\"viewBox\", \"0 -5 10 10\")\n", " .attr(\"refX\", 20)\n", " .attr(\"refY\", 0)\n", " .attr(\"markerUnits\", \"strokeWidth\")\n", " .attr(\"markerWidth\", 6)\n", " .attr(\"markerHeight\", 6)\n", " .attr(\"orient\", \"auto\")\n", " .append(\"path\")\n", " .attr(\"d\", \"M0,-5L10,0L0,5\");\n", "\n", " // // Create definition for stub.\n", " svg.append(\"defs\").append(\"marker\")\n", " .attr(\"id\", \"stub\")\n", " .attr(\"viewBox\", \"-1 -5 2 10\")\n", " .attr(\"refX\", 15)\n", " .attr(\"refY\", 0)\n", " .attr(\"markerUnits\", \"strokeWidth\")\n", " .attr(\"markerWidth\", 6)\n", " .attr(\"markerHeight\", 6)\n", " .attr(\"orient\", \"auto\")\n", " .append(\"path\")\n", " .attr(\"d\", \"M 0,0 m -1,-5 L 1,-5 L 1,5 L -1,5 Z\");\n", "\n", " // Background\n", " svg.append(\"rect\")\n", " .attr(\"width\", \"100%\")\n", " .attr(\"height\", \"100%\")\n", " .attr(\"fill\", \"#ffffff\")\n", " .style(\"pointer-events\", \"all\")\n", " // Zoom + panning functionality\n", " .call(d3.zoom()\n", " .scaleExtent([min_zoom, max_zoom])\n", " .on(\"zoom\", zoomed))\n", " .on(\"dblclick.zoom\", null);\n", "\n", "\n", " function zoomed() {\n", " g.attr(\"transform\", d3.event.transform);\n", " }\n", "\n", " // g = svg object where the graph will be appended\n", " var g = svg.append(\"g\");\n", "\n", " var linkedByIndex = {};\n", " graph.links.forEach(function (d) {\n", " linkedByIndex[d.source + \",\" + d.target] = true;\n", " });\n", "\n", " function isConnected(a, b) {\n", " return linkedByIndex[a.index + \",\" + b.index] || linkedByIndex[b.index + \",\" + a.index] || a.index == b.index;\n", " }\n", "\n", " function ticked() {\n", " link.attr(\"x1\", function (d) {\n", " return d.source.x;\n", " })\n", " .attr(\"y1\", function (d) {\n", " return d.source.y;\n", " })\n", " .attr(\"x2\", function (d) {\n", " return d.target.x;\n", " })\n", " .attr(\"y2\", function (d) {\n", " return d.target.y;\n", " });\n", "\n", " node\n", " .attr(\"transform\", function (d) {\n", " return \"translate(\" + d.x + \", \" + d.y + \")\";\n", " });\n", " }\n", "\n", "\n", " simulation\n", " .nodes(graph.nodes)\n", " .on(\"tick\", ticked);\n", "\n", " simulation.force(\"link\")\n", " .links(graph.links);\n", "\n", " // Definition of links nodes text...\n", "\n", " var link = g.selectAll(\".link\")\n", " .data(graph.links)\n", " .enter().append(\"line\")\n", " .style(\"stroke-width\", nominal_stroke)\n", " .style(\"stroke\", default_link_color)\n", " .style(\"stroke-dasharray\", function (d) {\n", " if (['decreases', 'directlyDecreases', 'increases', 'directlyIncreases', 'negativeCorrelation',\n", " 'positiveCorrelation'].indexOf(d.relation) >= 0) {\n", " return \"none\"\n", " } else {\n", " return \"4, 4\"\n", " }\n", " })\n", " .attr(\"marker-start\", function (d) {\n", " if ('positiveCorrelation' == d.relation) {\n", " return \"url(#arrowhead)\"\n", " }\n", " else if ('negativeCorrelation' == d.relation) {\n", " return \"url(#stub)\"\n", " }\n", " else {\n", " return \"\"\n", " }\n", " })\n", " .attr(\"marker-end\", function (d) {\n", " if (['increases', 'directlyIncreases', 'positiveCorrelation', 'isA', 'partOf'].indexOf(d.relation) >= 0) {\n", " return \"url(#arrowhead)\"\n", " } else if (['decreases', 'directlyDecreases', 'negativeCorrelation'].indexOf(d.relation) >= 0) {\n", " return \"url(#stub)\"\n", " } else {\n", " return \"\"\n", " }\n", " });\n", "\n", " var node = g.selectAll(\".nodes\")\n", " .data(graph.nodes)\n", " .enter().append(\"g\")\n", " .attr(\"class\", \"node\")\n", " // Next two lines -> Pin down functionality\n", " .on('dblclick', releasenode)\n", " .call(node_drag);\n", "\n", " var circle = node.append(\"path\")\n", " .attr(\"d\", d3.symbol()\n", " .size(function (d) {\n", " return Math.PI * Math.pow(size(d.size) || nominal_base_node_size, 2);\n", " })\n", " )\n", " .attr(\"class\", function (d) {\n", " return d.function\n", " })\n", " .style('fill', function (d) {\n", " return function_colors[d.function]\n", " })\n", " .style(\"stroke-width\", nominal_stroke)\n", " .style(\"stroke\", color_circunferencia);\n", "\n", " var text = node.append(\"text\")\n", " .attr(\"class\", \"node-name\")\n", " // .attr(\"id\", nodehashes[d])\n", " .attr(\"fill\", \"black\")\n", " .attr(\"dx\", 12)\n", " .attr(\"dy\", \".35em\")\n", " .text(function (d) {\n", " return getCanonicalName(d)\n", " });\n", "\n", " // Highlight on mouseenter and back to normal on mouseout\n", " node.on(\"mouseenter\", function (d) {\n", " set_highlight(d);\n", " })\n", " .on(\"mousedown\", function () {\n", " d3.event.stopPropagation();\n", " }).on(\"mouseout\", function () {\n", " exit_highlight();\n", " });\n", "\n", " function exit_highlight() {\n", " highlight_node = null;\n", " if (focus_node === null) {\n", " if (highlight_node_boundering != color_circunferencia) {\n", " circle.style(\"stroke\", color_circunferencia);\n", " text.style(\"fill\", \"black\");\n", " link.style(\"stroke\", default_link_color);\n", " }\n", " }\n", " }\n", "\n", " function set_highlight(d) {\n", " if (focus_node !== null) d = focus_node;\n", " highlight_node = d;\n", "\n", " if (highlight_node_boundering != color_circunferencia) {\n", " circle.style(\"stroke\", function (o) {\n", " return isConnected(d, o) ? highlight_node_boundering : color_circunferencia;\n", " });\n", " text.style(\"fill\", function (o) {\n", " return isConnected(d, o) ? highlight_text : \"black\";\n", " });\n", " link.style(\"stroke\", function (o) {\n", " return o.source.index == d.index || o.target.index == d.index ? highlighted_link_color : default_link_color;\n", " });\n", " }\n", " }\n", "\n", "\n", " // Freeze the graph when space is pressed\n", " function freezeGraph() {\n", " // Space button Triggers STOP\n", " if (d3.event.keyCode == 32) {\n", " simulation.stop();\n", " }\n", " }\n", "\n", " // Call freezeGraph when a key is pressed, freezeGraph checks whether this key is \"Space\" that triggers the freeze\n", " d3.select(window).on(\"keydown\", freezeGraph);\n", "}\n", "\n", "require.config({\n", " paths: {\n", " d3: '//cdnjs.cloudflare.com/ajax/libs/d3/4.5.0/d3.min'\n", " }\n", "});\n", "\n", "var elementInnerHTML = \"
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\"f618f39c33e74791dcba1fbe9d727a07c9eb2f3e0b415a6d7752e89ed99787c53592b44bf93bb6f6d1f5ea66a454795a4ad9b749ea7c0c19d2b2bcc10d646b0e\", \"name\": \"MAPT\", \"namespace\": \"HGNC\", \"variants\": [{\"identifier\": {\"name\": \"HBP00007\", \"namespace\": \"HBP\"}, \"kind\": \"pmod\"}]}, {\"function\": \"Protein\", \"id\": \"ede67fb639f29861d91976fefa16d8279b53ae13a659f35d70ed12e01bf3f339ffcf701fc54c7c4e908fee9902c02aac3e0022dcae5a7afa217ed2d4dba133b0\", \"name\": \"MAPT\", \"namespace\": \"HGNC\", \"variants\": [{\"identifier\": {\"name\": \"hyperphosphorylation\", \"namespace\": \"HBP\"}, \"kind\": \"pmod\"}]}, {\"function\": \"Protein\", \"id\": \"526bae251987f8c4f55f6e2451662fa55e087c57585beae7c389b020d73487c739834e9b8ec841783de6a5b5fb9df8b138e9eff4406a9ec5e606766575dcac0e\", \"name\": \"MAPT\", \"namespace\": \"HGNC\", \"variants\": [{\"identifier\": {\"name\": \"Ph\", \"namespace\": \"bel\"}, \"kind\": \"pmod\"}]}, {\"function\": \"Protein\", \"id\": \"df7a2c04f4438d51f2e9e042ebd8ae9456487148c38b1ee0deee645865eac74380f664a645c8c16f21cf9900e7a379af8b9e9c4a72dd57b7d1e0ba9738364fb0\", \"name\": \"NPAS4\", \"namespace\": \"HGNC\"}, {\"function\": \"Protein\", \"id\": \"d2586deea41500a6ea7755a94475bef3e256337b994748bb58034e8a43261cfea2cf38bc85241d08d9e06bdfc15b92df32297bceb6a3bf8848c3f2d6878b030b\", \"name\": \"TFEB\", \"namespace\": \"HGNC\"}, {\"function\": \"Protein\", \"id\": \"ee9a8850def1c6c0a93482d8d5c04086543f33fe5ab23c7c0f667149ea6d1b7b2eec7dfa67785a7199d05fff966640fc48cdd54d49b47adf5af492c9addf8337\", \"name\": \"Cyclic AMP-Dependent Protein Kinases\", \"namespace\": \"MESH\"}, {\"function\": \"Pathology\", \"id\": \"3196cc4c6a20279c822cae925a9b271d0224f2c8d468e3069a3ee460662be286b61db2f144c550686a9c624e58af4ffa7570f4f2384e1cb8ee40496f8cb3fa5e\", \"name\": \"Inflammation\", \"namespace\": \"MESH\"}, {\"function\": \"Pathology\", \"id\": \"0893d59040331bc1b155187396067458820ab2635e0138b840323082d33d44b964ab1240f5aeb64c5360e1340de40545835bc744c181abb910d64c923d55ff2b\", \"name\": \"Alzheimer Disease\", \"namespace\": \"MESHD\"}]}, \"#zvtuopsqryxfgcbe\", 1000, 650, {'Protein': '#1F77B4', 'Pathology': '#FF7F0E', 'BiologicalProcess': '#2CA02C', 'miRNA': '#D62728', 'Complex': '#98DF8A', 'Composite': '#9467BD', 'Reaction': '#000000', 'Gene': '#FFBB78', 'Abundance': '#AEC7E8', 'RNA': '#FF9896'});\n", "});" ], "text/plain": [ "" ] }, "execution_count": 44, "metadata": {}, "output_type": "execute_result" } ], "source": [ "mapt_ptm_controller_graph = get_upstream_causal_subgraph(graph, nodes)\n", "mapt_ptm_controller_graph.name = 'MAPT Post-Translational Modification Controllers'\n", "mapt_ptm_controller_graph.version = hbp_knowledge.VERSION\n", "mapt_ptm_controller_graph.summarize()\n", "to_jupyter(x)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "Get a list of controller proteins." ] }, { "cell_type": "code", "execution_count": 49, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "['CHRM1', 'CDK5', 'GSK3B', 'NPAS4', 'TFEB']\n" ] } ], "source": [ "controllers = [\n", " node.name\n", " for node in mapt_ptm_controller_graph\n", " if isinstance(node, Protein) and 'MAPT' != node.name and 'HGNC'== node.namespace.upper()\n", "]\n", "\n", "print(controllers)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "# TODO\n", "\n", "\n", "## INDRA Enrichment\n", "\n", "1. Generate query to find statements that have MAPT as an object and use a conversion statement\n", "2. Get bigger list of \n", "\n", "## Visualization of Relevant Chemical Space\n", "\n", "1. Load ExCAPE-DB\n", "2. Extract relationships from ExCAPE-DB related to these proteins\n", "3. Calculate chemical descriptors\n", "4. Show a t-SNE plot or related 2D depiction of chemical space" ] } ], "metadata": { "kernelspec": { "display_name": "Python 3", "language": "python", "name": "python3" }, "language_info": { "codemirror_mode": { "name": "ipython", "version": 3 }, "file_extension": ".py", "mimetype": "text/x-python", "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", "version": "3.7.1" } }, "nbformat": 4, "nbformat_minor": 2 }