31:T80d,md` ** Objective. ** We investigated the nature and extent of selective forces acting on the viral genes in _${cladeName}_ clade sequences by performing a series of comparative phylogenetic analyses on a median of ${d3.median (speciesCount, d=>d[cladeName])} _${cladeName}_ sequences from and a median of ${d3.median (speciesCount, d=>d["Reference"])} sequences from GISAID chosen to represent genomic diversity in SARS-CoV-2. ** Results. ** 1. There is evidence of **diversifying positive selection** acting on the _${cladeName}_ sequences, on **${selected_sites.length}** individual sites (there are ${polymorphic_sites.length} sites that are polymorphic in the amino-acid space among clade sequences; selection also incluses the basal branch of the clade) along the internal branches of the clade ([Table 1](#table1)). 2. ${has_full_meme ? "There is evidence of **diversifying positive selection** acting on the _ " + cladeName + "_ sequences, on **" + selected_sites_leaves.length +"** individual sites along **all** branches of the clade ([Table 7](#table7))." : "No full clade MEME data"} 3. When comparing the strength of selection on _${cladeName}_ to reference sequences along internal tree branches, **${diff_sites.length}** individual sites along the internal branches of the clade ([Table 2](#table2)) showed statistically significant differences. 4. Over the entire tree **${directional_sites.length}** sites show evidence of directional selection ([Table 3](#table3)). 5. Along the internal branches of the _${cladeName}_ clade, **${coevolve_sites.length}** pairs of sites showed evidence of **coevolution** ([Table 4](#table4)). 6. Along the internal branches of the _${cladeName}_ clade, **${negative_sites.length}** sites showed evidence of **negative selection** ([Table 5](#table5)). 7. Along the internal branches of the _${cladeName}_ clade, **${_.filter (busted_distribution_summary, (d)=>d.q <= 0.1).length}** genes/ORFs showed evidence of **episodic diversifying selection** (BUSTED, q-value ≤ 0.1, [Table 6](#table6)). ` 32:T8d1,{ if (site2view.length) return md`Site **${site2view}**, codon **${annotation_json[site2view].S} in gene/ORF ${annotation_json[site2view].G}**.
Pervasive selection test
FEL p-value ${float_format (annotation_json[site2view].bFEL.p)}, ω = ${report_ratio (annotation_json[site2view].bFEL.a, annotation_json[site2view].bFEL.b)}
Episodic diversifying selection test (internal branches)
MEME p-value ${float_format (annotation_json[site2view].bMEME.p)}, ω + = ${report_ratio (annotation_json[site2view].bMEME["a"], annotation_json[site2view].bMEME["b+"])}, p = ${float_format (annotation_json[site2view].bMEME["w+"])}, **${annotation_json[site2view].bMEME.br}** selected branches ${"lMEME" in annotation_json[site2view] ? "Episodic diversifying selection test (all branches)
MEME p-value (all branches) " + float_format (annotation_json[site2view].lMEME.p) + ", ω + = " + report_ratio (annotation_json[site2view].lMEME['a'], annotation_json[site2view].lMEME['b+']) + ", p = " + float_format (annotation_json[site2view].lMEME['w+']) + ", ** " + annotation_json[site2view].lMEME.br +" ** selected branches" : ""}
Test for different selective pressures between ${cladeName} and reference branches
${cfel_site_report(site2view)}
Directional selection test
${fade_site_report(site2view)}
Property importance test
${prime_site_report(site2view)}
Amino-acid composition

_${cladeName}_: ${freq_report (annotation_json [site2view].aa[cladeName])}
_Reference_: ${freq_report (annotation_json [site2view].aa["Reference"])}

`; return md`Select a site to view detailed information on it`; }33:T44a,table (selected_sites, { limit: 5000, enableCSVDownload: true, sort: true, enableFilter: false, columns: [ { key: 'coordinate', name: 'Coordinate (SARS-CoV-2)' }, { key: 'gene', name: 'Gene/ORF' }, { key: 'site', name: 'Codon (in gene/ORF)' }, { key : 'meme_branches', name : '# of selected branches', render : (val)=>d3.format ("d") (val) }, { key : 'p', name : 'p-value', render : (val)=>d3.format (".3g") (val) }, { key : 'q', name : 'q-value', render : (val)=>d3.format (".3g") (val) }, { key : 'prime', name : 'Properties', render : (val)=>_.map (val, (d)=>{if (d[2]) return d[0] + (d[2]>0 ? " (constrained) " : " (changing)"); else return 'overall';}).join (", ") } ] });34:T416,md` 1. ** Coordinate (SARS-CoV-2)** : the starting coordinate of the codon in the NCBI reference SARS-CoV-2 genome 2. ** Gene/ORF ** : which gene or ORF does this site belong to 3. ** Codon (in gene/ORF) ** : the location of the codon in the corresponding Gene/ORF 4. ** % of branches with ω>1 ** : the fraction of tree branches (internal branches in the ${cladeName} clade) that have evidence of diversifying positive selection at this site (100% -- pervasive selection, <100% --episodic selection). 5. ** p-value ** : the p-value for the likelihood ratio test that a non-zero fraction of branches have ω > 1 (i.e. episodic diversifying selection at this branch). This is not corrected for multiple testing; the MEME test is generally conservative on real data. 6. ** q-value ** : multiple-test corrected q-value (Benjamini-Hochberg) 7. ** Properties ** : which, if any, of the five compositive biochemical properties from [Atchley et al](https://www.pnas.org/content/102/18/6395) are conserved or changed at this site. `35:T593,table (busted_distribution_summary, { limit: 5000, enableCSVDownload: true, sort: true, enableFilter: false, columns: [ { key: 'file', name: 'Segment' }, { key: 'omega1', name: '⍵1', render : (val)=>d3.format (".3g") (val) }, { key: 'proportion1', name: 'p1', render : (val)=>d3.format (".3p") (val) }, { key: 'omega2', name: '⍵2', render : (val)=>d3.format (".3g") (val) }, { key: 'proportion2', name: 'p2', render : (val)=>d3.format (".3p") (val) }, { key: 'omega3', name: '⍵3', render : (val)=>d3.format (".3g") (val) }, { key: 'proportion3', name: 'p3', render : (val)=>d3.format (".3p") (val) }, { key : 'p', name : 'p-value', render : (val)=>val <= 0.05 ? '' + d3.format (".3g") (val) + '' : d3.format (".3g") (val) }, { key : 'q', name : 'q-value', render : (val)=>val <= 0.2 ? '' + d3.format (".3g") (val) + '' : d3.format (".3g") (val) }, ] });36:T4db,table (selected_sites_leaves, { limit: 5000, enableCSVDownload: true, sort: true, enableFilter: false, columns: [ { key: 'coordinate', name: 'Coordinate (SARS-CoV-2)' }, { key: 'gene', name: 'Gene/ORF' }, { key: 'site', name: 'Codon (in gene/ORF)' }, { key : 'meme_branches', name : '# of selected branches', render : (val)=>d3.format ("d") (val) }, { key : 'p', name : 'p-value', render : (val)=>d3.format (".3g") (val) }, { key : 'pMEME', name : 'p-value/int', render : (val)=>d3.format (".3g") (val) }, { key : 'q', name : 'q-value', render : (val)=>d3.format (".3g") (val) }, { key : 'prime', name : 'Properties', render : (val)=>_.map (val, (d)=>{if (d[2]) return d[0] + (d[2]>0 ? " (constrained) " : " (changing)"); else return 'overall';}).join (", ") } ] });37:T533,md` 1. ** Coordinate (SARS-CoV-2)** : the starting coordinate of the codon in the NCBI reference SARS-CoV-2 genome 2. ** Gene/ORF ** : which gene or ORF does this site belong to 3. ** Codon (in gene/ORF) ** : the location of the codon in the corresponding Gene/ORF 4. ** % of branches with ω>1 ** : the fraction of tree branches (internal branches in the ${cladeName} clade) that have evidence of diversifying positive selection at this site (100% -- pervasive selection, <100% --episodic selection). 5. ** p-value ** : the p-value for the likelihood ratio test that a non-zero fraction of branches have ω > 1 (i.e. episodic diversifying selection at this branch). This is not corrected for multiple testing; the MEME test is generally conservative on real data. 6. ** p-value/int ** : the p-value for the likelihood ratio test that a non-zero fraction of **internal** branches have ω > 1 (i.e. episodic diversifying selection at this branch). This is not corrected for multiple testing; the MEME test is generally conservative on real data. 7. ** q-value ** : multiple-test corrected q-value (Benjamini-Hochberg) 8. ** Properties ** : which, if any, of the five compositive biochemical properties from [Atchley et al](https://www.pnas.org/content/102/18/6395) are conserved or changed at this site. `38:T1572,{ let dim = treeDim.length ? _.map (treeDim.split ("x"), (d)=>+d) : null; let tree = tree_object[0]; var t = tree.render("#tree_container_0", dim ? { height:dim[0] || 1024, width:dim[1] || 600, 'show-scale' : true, 'is-radial' : false, 'left-right-spacing': 'fit-to-size', 'top-bottom-spacing': 'fit-to-size', 'node_circle_size' : (n)=>0 } : { //height:1024, width:800, 'show-scale' : true, 'left-right-spacing': 'fit-to-size', //'top-bottom-spacing': 'fit-to-size', 'is-radial' : false, 'node_circle_size' : (n)=>0 }); const bs = (n) => { if (tree.is_leafnode (n)) { return 3; } return 1; }; let siteID = summary_json[site2segment [site2view]? site2segment [site2view] : segment_id].subs[site2view]; let treeTags = summary_json [segment_id].tree_tags; let nodeStates = null; if (siteID) { nodeStates = {}; let node_labels = siteID; function recurse_node (node) { if (node.data.name in node_labels) { nodeStates[node.data.name] = node_labels[node.data.name]; } else { nodeStates[node.data.name] = nodeStates[node.parent.data.name]; } _.each (node.children, (c)=>recurse_node(c)); } recurse_node(tree.nodes); if (doAA) { for (let node in nodeStates) { nodeStates[node] = nodeStates[node] in translation_table ? translation_table[nodeStates[node]] : '?'; } } } let c10 = d3.scaleOrdinal(d3.schemeDark2); //var c10 = d3.scaleOrdinal(d3.schemeDark2); //t.node_label = n=>n.data.name.substr (0,3); t.node_bubble_size = bs; t.phylotree.node_bubble_size = bs; t.options["draw-size-bubbles"] = nodeStates ? true : false; //t.font_size = 8; //t.spacing_x (7); t.phylotree.branch_length_accessor = n=> { //console.log (summary_json[segment_id]); let bl = tree_object[1][n.data.name][2]; if (bl > 0.25) { n.data.censored_bl = true; return 0.25; } else { n.data.censored_bl = false; } return bl; } t.node_label ((n)=>{ if (nodeStates) { return (n.data.name) in nodeStates ? nodeStates[n.data.name] : n.data.name;// + " (" + n.data.name + ")"; } if (n.children && n.children.length) {return "";} let pieces = n.data.name.split ("_"); if (n.data.name.indexOf ("epi") == 0) { return pieces[2] || ""; } return pieces[pieces.length-4] || ""; //return n.data.name; //return ""; }); function sort_nodes (asc) { tree.traverse_and_compute (function (n) { var d = 1; if (n.children && n.children.length) { d += d3.max (n.children, function (d) { return d["count_depth"];}); } n["count_depth"] = d; }); tree.resort_children (function (a,b) { return (a["count_depth"] - b["count_depth"]) * (asc ? 1 : -1); }); } sort_nodes (true); tree.traverse_and_compute ((n) => { //if (!tree.is_leafnode (n) && !n.tagged_view && n.parent && n.parent.tagged_view) { //n.notshown = true; //} }); t.style_nodes ((e,n) => { if (n.data.name in tree_object[1]) { let binfo = tree_object[1][n.data.name]; e.selectAll("text").selectAll("title").data([n.data.name]).enter().append("title").text ((d)=>d); if (nodeStates) { e.style ('fill', c10 (nodeStates[n.data.name])); if (binfo[0].length) { e.selectAll ("circle").style ('fill', species_colors (binfo[0])); } } else { if (binfo[0].length) { e.style ('fill', species_colors (binfo[0])); } } } //} }); t.style_edges ((e,d) => { let subs = subsByBranch[d.target.data.name], sub_count = 0, ttext = null; if (subs) { sub_count = subs.length; ttext = "Subs at " + subs.join (", "); } if (d.target.data.name in treeTags) { if (treeTags[d.target.data.name][3].length) { ttext += "\nMEME selection at sites " + _.map (treeTags[d.target.data.name][3], (s)=>annotation_json [s].G + "/" + annotation_json [s].S).join (", "); } sub_count = treeTags[d.target.data.name][3].length; } if (nodeStates) { if (nodeStates[d.target.data.name] != nodeStates[d.source.data.name]) { e.style ('stroke-width',5); } else { e.style ('stroke-width',null); } if (d.target.data.name in treeTags) { if ( treeTags[d.target.data.name][3].indexOf (+site2view) >= 0) { e.style ('stroke','darkred'); } } } else { if (d.target.data.name in tree_object[1]) { let binfo = tree_object[1][d.target.data.name]; e.style ('stroke-width', 1 + sub_count); } //e.selectAll("title").text ("p = " + p); } if (d.target.data.censored_bl) { e.style ('stroke-dasharray',10); } if (ttext) { e.selectAll("title").text (ttext); } }); t.placenodes(); t.update(); return t; }39:T5a8,fragments = { let result = _.sortBy(_.flatten (_.map (summary_json, (d,k)=> { let ranges = _.filter (d.map, (i)=>i>=0); let my_range = []; ranges.push (1e100); let last_check = ranges[0]; _.reduce (ranges, (accumulator, value)=> { if ((value - accumulator) % 3 == 0) { return value; } else { let tag = k.split ("_"); if (tag.length > 3) { tag = tag[1]+"/"+tag[2]; } else { tag = k.split (".")[0]; } my_range.push ([k, last_check, accumulator + 2, d["busted"]["p"], 0, tag, d["rates"]["mean-omega"]["Foreground"] ]); last_check = value; return value; } }, ranges[0]-3); return my_range; } ), true), (d)=>d[1]); let index = {}; let count = 0; _.each (result, (d) => { d.push (count++); }); return result; }3a:T576,plotPie = (data)=>vegalite ({ "data": { "values": data }, "encoding": { "theta": {"field": "proportion", "type": "quantitative", "stack": true}, "color": {"field": "omega", "type": "quantitative", //"sort": "descending", "title" : "dN/dS", "scale": { "domain" : [0,4], "type" : "sqrt", "clamp" : true, //"domainMid": 1, "scheme": "lightmulti" } }}, "layer" : [ { "mark": {"type": "arc", "innerRadius": 40, "outerRadius" : 60, tooltip : true, padAngle : 0.0, strokeWidth : 1, strokeOpacity: 1}, "encoding" : { "stroke" : {value : "black"}, } }, { "mark": {"type": "text", "outerRadius" : 70, "fontSize" : 18}, "encoding": { "color" : {"value" : "black"}, "text": { "field": "omega", "type": "nominal", "format" : ".2f", "condition": {"test": "datum['omega'] <= 1.", "value": ""}, } } }, { "mark": {"type": "text", "outerRadius" : 20, "fontSize" : 18}, "encoding": { "color" : {"value" : "black"}, "text": { "field": "proportion", "type": "nominal", "format" : ".2p", "condition": {"test": "datum['omega'] <= 1.", "value": ""}, } } } ], "view": {"stroke": null} })3b:T407,{ let fasta = await d3.text(analysis_info.b + analysis_name + "/" + segment_id + ".combined.fas"); fasta = _.map (fasta.split ('\n'), (l)=>{ if (l[0]=='>') { let p = l.substr (1).split ('/'); if (p.length > 1) { let s = p[p.length-1].split('|'); return '>' + p[1] + "|" + s[s.length-1]; } else { p = l.substr (1).split ('_'); p = p.splice (3); p.splice (-2,2); return '>REF|' + p.join("/"); } return l; } //accumulator += l.replace (" ", ""); if (l.length) { return _.map (_.range (0,l.length,3), (s)=>translate_ambiguous_codon_gap (l.substr (s,3))).join (""); } return ""; }).join ("\n"); ReactDOM.render( React.createElement( a.default, {fasta: a.fastaParser(fasta), site_color:a.colors.amino_acid_color, text_color:a.colors. amino_acid_text_color, centerOnSite: 50 }, null ), document.getElementById('alignment')); }3c:[] 2f:{"title":"Visualizing selection analysis results for evolution of the 501Y.V2 clade","cells":[{"id":0,"value":"md`# Visualizing selection analysis results for evolution of the ${cladeName} clade\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3303,"value":"viewof analysis_name = {\n const dd3 = select({\n title: \"Display this analysis.\",\n options: [\n { label: \"B.1.351\", value: 'B1351-Feb2020'},\n { label: \"B.1.1.7\", value: 'B117-Feb2020'},\n { label: \"P1\", value: 'P1-Feb2020'},\n { label: \"P1-separate\", value: 'P1'},\n { label: \"P2\", value: 'P2'},\n { label: \"P2vB.1.1.28\", value: 'P2v128'}\n ],\n value: 'B.1.351'\n });\n dd3.input.style.fontSize = \"18px\";\n return dd3;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":3281,"value":"analysis_info = {\n let base_url = \"https://data.hyphy.org/web/SARS-CoV-2/clades/\";\n let urls = analysis_name;\n yield md`>Loading summary data...

`; \n let summary = await d3.json (base_url + analysis_name + \"-summary.json\");\n yield md`>Loading annotation data...

`;\n let annotation = await d3.json ((base_url + analysis_name + \"-annotation.json\"));\n annotation = _.chain (annotation).toPairs().filter ((d)=>'bFEL' in d[1]).fromPairs().value();\n let res = md`Loaded data on ${_.size(summary)} segments and ${_.size(annotation)} sites`;\n res.s = summary;\n res.a = annotation;\n res.b = base_url;\n yield res;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2704,"value":"$31","pinned":false,"hidden":false,"mode":"ojs"},{"id":2233,"value":"md`### Segment information`","pinned":false,"hidden":false,"mode":"ojs"},{"id":966,"value":"viewof segment_id = {\n const dd3 = select({\n title: \"View this genomic segment\",\n options: _.map (_.uniqBy (fragments,\"0\"), (g)=>g[0])\n \n });\n dd3.input.style.fontSize = \"30px\";\n dd3.input.style.marginTop = \"8px\";\n return dd3;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2280,"value":"md`The BUSTED p-value for episodic selection is **${float_format(summary_json[segment_id][\"busted\"][\"p\"])}**. The RELAX p-value is **${float_format(summary_json[segment_id][\"relax\"][\"p\"])}** and the relaxation/intensification parameters was **${float_format(summary_json[segment_id][\"relax\"][\"K\"])}**, impying that selection in ${cladeName} was **${summary_json[segment_id][\"relax\"][\"K\"] > 1 ? \"intensified\" : \"relaxed\"}** relative to the reference branches.`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3489,"value":"md`**Figure 0.** segment alignment view`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3441,"value":"html`

`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2236,"value":"md`### Site-level information`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1972,"value":"\nviewof site2viewIDX = autoSelect({\n options: _.flatten ([\"Overall for \" + segment_id,_.map (site2segment, (v,k)=>k + \" \" + annotation_json[k].G + \"/\" + annotation_json[k].S)]),\n title: `View this site (in SARS-CoV-2 reference coordinates)`,\n placeholder: \"Select a site (or overall)\"\n})\n","pinned":false,"hidden":false,"mode":"ojs"},{"id":2301,"value":"$32","pinned":false,"hidden":false,"mode":"ojs"},{"id":2657,"value":"viewof treeDim = text({placeholder : \"1024 x 800\", description: \"Tree dimension (height x width in pixels), leave blank to auto-scale\", submit: \"Resize\"})","pinned":false,"hidden":false,"mode":"ojs"},{"id":2067,"value":"viewof doAA = checkbox({\n options: [{ value: \"toggle\", label: \"Label tree with amino-acids\" }]\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":2855,"value":"md`Branches that have experienced at least one substittuion are shown in thicker lines. Branches that have MEME-based support for episodic selection at a given site, are shown in **dark red**. Mouse over branches to show additional information if available (e.g substitutions over those branches, and MEME episodic selection support).`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1941,"value":"trendLegend = swatches({\n color: species_colors,\n title: \"Viral species\",\n //tickFormat: \"%\"\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":15,"value":"html`\n \n

\n`\n","pinned":false,"hidden":false,"mode":"ojs"},{"id":870,"value":"html`\n \n

`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2239,"value":"md`### Result tables`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1693,"value":"table1=md`**Table 1** List of sites found to be under diversifying positive selection by [MEME](https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002764) (p≤0.05) along internal branches in _${cladeName}_, as well as biochemical properties that are _important_ at this site (via the [PRIME method](http://hyphy.org/w/index.php/PRIME))`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1028,"value":"$33","pinned":false,"hidden":false,"mode":"ojs"},{"id":2973,"value":"$34","pinned":false,"hidden":false,"mode":"ojs"},{"id":2244,"value":"table2=md`**Table 2** List of sites found to be selected differentially along internal branches between _${cladeName}_ and reference sequences (FDR ≤ 0.2) using the [Contrast-FEL method](https://dl.dropbox.com/s/o3q9fwgzur851eo/msaa263.pdf)`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2249,"value":"table (diff_sites,\n {\n limit: 5000,\n enableCSVDownload: true,\n sort: true,\n enableFilter: false,\n columns: [\n {\n key: '0',\n name: 'Coordinate (SARS-CoV-2)'\n },\n {\n key: '6',\n name: 'Gene/ORF'\n },\n {\n key: '5',\n name: 'Codon (in gene/ORF)'\n },\n {\n key : '7',\n name : 'Ratio of ω (' + cladeName + ' : reference)',\n },\n {\n key : '4',\n name : 'p',\n render : (val)=>d3.format (\".3g\") (val)\n },\n {\n key : '8',\n name : 'q',\n render : (val)=>d3.format (\".3g\") (val)\n }\n ]\n});","pinned":false,"hidden":false,"mode":"ojs"},{"id":3004,"value":"md`\n\n1. ** Coordinate (SARS-CoV-2)** : the starting coordinate of the codon in the NCBI reference SARS-CoV-2 genome\n2. ** Gene/ORF ** : which gene or ORF does this site belong to\n3. ** Codon (in gene/ORF) ** : the location of the codon in the corresponding Gene/ORF\n4. ** Ratio of ω (${cladeName} : reference) ** : the ratio of site-level ω estimates for the two sets of branches. If this ratio is >1, then selection on ${cladeName} is stronger. These values are highly imprecise and should be viewed as qualitative measures.\n5. ** p-value ** : the p-value for the likelihood ratio test that ω ratios between the internal branches of the two clades are different. This is not corrected for multiple testing.\n6. ** q-value ** : multiple-test corrected q-value (Benjamini-Hochberg)\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2674,"value":"md` **Table 3** List of sites found to be evolving under directional selection in the entire tree, using a FUBAR-like implementation of the [DEPS method](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515872/). The tree was rooted on the genome reference sequence for this analysis.`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2677,"value":"table (directional_sites,\n {\n limit: 5000,\n enableCSVDownload: true,\n sort: true,\n enableFilter: false,\n columns: [\n {\n key: '0',\n name: 'Coordinate (SARS-CoV-2)'\n },\n {\n key: '3',\n name: 'Gene/ORF'\n },\n {\n key: '4',\n name: 'Codon (in gene/ORF)'\n },\n {\n key : '1',\n name : 'Target amino-acids',\n }\n ]\n});","pinned":false,"hidden":false,"mode":"ojs"},{"id":3013,"value":"md`\n\n1. ** Coordinate (SARS-CoV-2)** : the starting coordinate of the codon in the NCBI reference SARS-CoV-2 genome\n2. ** Gene/ORF ** : which gene or ORF does this site belong to\n3. ** Codon (in gene/ORF) ** : the location of the codon in the corresponding Gene/ORF\n4. ** \tTarget amino-acid ** : which amino-acids have statistical support (Bayes Factor ≥ 100) for accelerated evolution towards them.\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2829,"value":"table4=md`**Table 4** Pairs of sites found to have epistatic (co-evolving) substitution patterns by [BGM method](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732215/)`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2834,"value":"table (coevolve_sites,\n {\n limit: 5000,\n enableCSVDownload: true,\n sort: true,\n enableFilter: false,\n columns: [\n {\n key: '10',\n name: 'Gene/ORF'\n },\n {\n key: '11',\n name: 'Codon 1 (in gene/ORF)'\n },\n {\n key: '12',\n name: 'Codon 2 (in gene/ORF)'\n },\n {\n key: '4',\n name: 'Posterior probability of non-independence',\n render : (val)=>d3.format (\".3g\") (val)\n },\n ]\n});","pinned":false,"hidden":false,"mode":"ojs"},{"id":3021,"value":"md`\n\n1. ** Gene/ORF ** : which gene or ORF does this site belong to\n2. ** Codon 1/2 (in gene/ORF) ** : the location of the two interacting codons in the corresponding Gene/ORF\n3. ** \tPosterior probability of non-independence ** : estimated posterior probability that substitutions which occur on the interior branches of the ${cladeName} clade are **not** independent.\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3233,"value":"table5=md`**Table 5** List of sites found to be under pervasive negative selection by [FEL](https://academic.oup.com/mbe/article/22/5/1208/1066893) (p≤0.05) along internal branches in _${cladeName}_`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3239,"value":"table (negative_sites,\n {\n limit: 5000,\n enableCSVDownload: true,\n sort: true,\n enableFilter: false,\n columns: [\n {\n key: 'coordinate',\n name: 'Coordinate (SARS-CoV-2)'\n },\n {\n key: 'gene',\n name: 'Gene/ORF'\n \n },\n {\n key: 'site',\n name: 'Codon (in gene/ORF)'\n },\n {\n key: 'alpha',\n name: 'Synonymous rate',\n render : (val)=>d3.format (\".3g\") (val)\n },\n {\n key: 'beta',\n name: 'Non-synonymous rate',\n render : (val)=>d3.format (\".3g\") (val)\n },\n {\n key : 'p',\n name : 'p-value',\n render : (val)=>d3.format (\".3g\") (val)\n },\n {\n key : 'q',\n name : 'q-value',\n render : (val)=>d3.format (\".3g\") (val)\n }\n ]\n});","pinned":false,"hidden":false,"mode":"ojs"},{"id":3269,"value":"md`\n\n1. ** Coordinate (SARS-CoV-2)** : the starting coordinate of the codon in the NCBI reference SARS-CoV-2 genome\n2. ** Gene/ORF ** : which gene or ORF does this site belong to\n3. ** Codon (in gene/ORF) ** : the location of the codon in the corresponding Gene/ORF\n4. ** Synonymous rate ** : Site estimate for the synonymous substitution rate (α). These values are highly imprecise and should be viewed as qualitative measures.\n4. ** Non-synonymous rate ** : Site estimate for the non-synonymous substitution rate (β). These values are highly imprecise and should be viewed as qualitative measures.\n5. ** p-value ** : the p-value for the likelihood ratio test that β/&alpha ≠ 1\n6. ** q-value ** : multiple-test corrected q-value (Benjamini-Hochberg)\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2173,"value":"table6=md`**Table 6** [BUSTED](https://academic.oup.com/mbe/article/32/5/1365/1134918) selection results on the SARS-CoV-2 clade across segments`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1663,"value":"$35","pinned":false,"hidden":false,"mode":"ojs"},{"id":3394,"value":"table7=md`**Table 7** List of sites found to be under diversifying positive selection by [MEME](https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002764) (p≤0.05) along **all** branches in _${cladeName}_, as well as biochemical properties that are _important_ at this site (via the [PRIME method](http://hyphy.org/w/index.php/PRIME))`","pinned":false,"hidden":false,"mode":"ojs"},{"id":3397,"value":"$36","pinned":false,"hidden":false,"mode":"ojs"},{"id":3400,"value":"$37","pinned":false,"hidden":false,"mode":"ojs"},{"id":3027,"value":"md`\n

\n### Data and libraries \n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":5,"value":"md`---`","pinned":false,"hidden":false,"mode":"ojs"},{"id":9,"value":"d3 = require (\"d3\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":11,"value":"phylotree=require (\"https://dl.dropboxusercontent.com/s/i528j2lqnyzknit/phylotree.js\")\n//require (\"phylotree/build/phylotree.js\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":13,"value":"_=require(\"lodash\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":78,"value":"//resolve(\"phylotree@0.1/phylotree.css\")\n//require (\"https://dl.dropbox.com/s/mjhii51tjy1o5gt/phylotree.js\")\nhtml`\n\n`","pinned":false,"hidden":false,"mode":"ojs"},{"id":2627,"value":"site2view = site2viewIDX.split (\" \")[0]","pinned":false,"hidden":false,"mode":"ojs"},{"id":1905,"value":"tree_object = [new phylotree.phylotree(summary_json[site2segment [site2view]? site2segment [site2view] : segment_id][\"tree\"]), summary_json[site2segment [site2view]? site2segment [site2view] : segment_id][\"tree_tags\"]]","pinned":false,"hidden":false,"mode":"ojs"},{"id":127,"value":"$38","pinned":false,"hidden":false,"mode":"ojs"},{"id":874,"value":"import { table } from \"@gampleman/table\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":174,"value":"import {select,checkbox, autoSelect, text} from \"@jashkenas/inputs\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":488,"value":"vegalite = require(\"vega-embed\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":1793,"value":"selection_profile = {\n let summary = [];\n _.each (fragments, (d,i)=> {\n _.each ([\"HKU1\",\"OC43\",\"SARS\",\"SARS-CoV-2\"], (s)=> {\n let T = summary_json[d[0]].rates[\"T\"][s];\n if (T > 0) {\n summary.push ({'segment' : i+1, 'x': d[1], 'omega' : summary_json[d[0]].rates[\"mean-omega\"][s], 'T' : T, 's': s});\n summary.push ({'segment' : i+1, 'x': d[2], 'omega' : summary_json[d[0]].rates[\"mean-omega\"][s], 'T' : T, 's': s});\n\n } else {\n summary.push ({'segment' : i+1, 'x': d[1], 'T' : T, 's': s});\n summary.push ({'segment' : i+1, 'x': d[2], 'T' : T, 's': s});\n\n }\n })});\n return summary;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":684,"value":"$39","pinned":false,"hidden":false,"mode":"ojs"},{"id":2288,"value":"float_format = d3.format (\".3g\");","pinned":false,"hidden":false,"mode":"ojs"},{"id":2438,"value":"cladeName=annotation_json ? _.find (_.keys(_.sample (annotation_json)[\"cdn\"]), (d)=>d!=\"Reference\") : \"...\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":2217,"value":"$3a","pinned":false,"hidden":false,"mode":"ojs"},{"id":1876,"value":"prime_annotation = _.map (summary_json[_.first (_.keys(summary_json))][\"prime-properties\"], (d)=>d.split (\" \")[2])","pinned":false,"hidden":false,"mode":"ojs"},{"id":2321,"value":"report_ratio = (a,b)=> {\n if (a == 0 && b == 0) return 'N.D.';\n if (a == 0) return 'Infinite';\n return float_format (b/a);\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":1929,"value":"species = _.sortBy (_.filter (_.uniq (_.map (summary_json[\"S\"][\"tree_tags\"], (d)=>d[0])), (d)=>d.length))","pinned":false,"hidden":false,"mode":"ojs"},{"id":2799,"value":"speciesCount = _.map (summary_json, (seg,k)=>_.countBy (_.filter (seg[\"tree_tags\"], (d)=>d[1] == false), (d)=>d[0]))","pinned":false,"hidden":false,"mode":"ojs"},{"id":1937,"value":"species_colors = d3.scaleOrdinal(d3.schemeCategory10).domain (species);","pinned":false,"hidden":false,"mode":"ojs"},{"id":1152,"value":"busted_distributions = _.flatten (_.map (summary_json, (d,k)=>{\n return _.map (d[\"rates\"][\"busted\"][\"Test\"], (dd)=>{\n return {\n file: k,\n omega: dd.omega,\n proportion: dd.proportion,\n p: d[\"busted\"][\"p\"]\n };\n });\n})); ","pinned":false,"hidden":false,"mode":"ojs"},{"id":2230,"value":"relax_distributions = _.flatten (_.map (summary_json, (d,k)=>{\n return _.flatten (_.map (d[\"rates\"][\"relax\"], (dd2,kk)=>{\n \n return _.map (dd2, (dd)=>{return {\n file: k,\n species: kk,\n omega: dd.omega,\n proportion: dd.proportion,\n p: d[\"relax\"][\"p\"]\n }\n });\n }))})); ","pinned":false,"hidden":false,"mode":"ojs"},{"id":1666,"value":"busted_distribution_summary = {\n let bds = _.sortBy (_.map (summary_json, (d,k)=>{\n let dd = d[\"rates\"][\"busted\"][\"Test\"];\n return {\n file: k,\n omega1: dd[0].omega,\n proportion1: dd[0].proportion,\n omega2: dd[1].omega,\n proportion2: dd[1].proportion,\n omega3: dd[2].omega,\n proportion3: dd[2].proportion,\n p: d[\"busted\"][\"p\"],\n };\n }), (d)=>d.p); \n return _.map (bds, (record, i)=> {\n record['q'] = record['p'] * bds.length / (i+1); \n return record;\n });\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":764,"value":"conserved_sites = _.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=>_.uniq (_.flatten (_.map (species, (sp)=>_.uniq (_.keys (s[1].aa ? s[1].aa[sp] : []))))).length == 1, (d)=>[+d[0]])","pinned":false,"hidden":false,"mode":"ojs"},{"id":2195,"value":"site2segment = {\n let r = {};\n _.each (summary_json, (d,s)=> {\n _.each (d.map, (c)=> {\n if (c >= 0 && (c in annotation_json)) {\n r[c] = s; \n }\n });\n });\n \n return r;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2407,"value":"site2alignment = {\n let r = {};\n let offset = 1;\n let last_segment = \"\";\n let only_sites = _.sortBy (_.map (annotation_json, (d,k)=>[k,d.index]), (s)=>+s.k);\n //return only_sites;\n _.each (only_sites, (d)=> {\n if (site2segment[d[0]] != last_segment) {\n if (last_segment && last_segment.length) {\n offset += summary_json [last_segment].map.length;\n }\n last_segment = site2segment[d[0]];\n \n }\n r [d[0]] = offset + d[1];\n });\n \n return r;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":3621,"value":"p_cut = 0.05","pinned":false,"hidden":false,"mode":"ojs"},{"id":780,"value":"selected_sites = {\n let s = _.map (_.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=>s[1].bMEME.p<=0.05), (d)=>{return {'coordinate' : +d[0],'p' : d[1].bMEME.p,'meme_branches' : d[1].bMEME[\"br\"],'gene': d[1].G, 'site' : d[1].S, 'fel_p' : d[1].bFEL.p, 'fel_n' : d[1].bFEL.b < d[1].bFEL.a, 'prime' : _.map(_.filter (_.map (d[1].prime.p, (p,i)=>[i,p,i>0 ? d[1].prime['lambda'][i-1] : null]), (pr)=>pr[1]<0.05), (d)=>{if (d[0]>0) d[0] = prime_annotation [d[0]-1]; else d [0] = \"Overall\"; return d;})};});\n s = _.sortBy (s, (d)=>d.p);\n let tests = summary_json[segment_id].map.length;\n _.each (s, (d,i)=> {\n d.q = Math.min (1,d.p * (tests/(i+1)));\n });\n return _.sortBy (s, (d)=>d.site);\n }","pinned":false,"hidden":false,"mode":"ojs"},{"id":3379,"value":"selected_sites_leaves = {\n let s = _.map (_.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=>(\"lMEME\" in s[1]) && s[1].lMEME.p<=0.05), (d)=>{return {'coordinate' : +d[0],'p' : d[1].lMEME.p,'meme_branches' : d[1].lMEME[\"br\"],'gene': d[1].G, 'site' : d[1].S, 'pMEME' : d[1].bMEME.p, 'fel_p' : d[1].bFEL.p, 'fel_n' : d[1].bFEL.b < d[1].bFEL.a, 'prime' : _.map(_.filter (_.map (d[1].prime.p, (p,i)=>[i,p,i>0 ? d[1].prime['lambda'][i-1] : null]), (pr)=>pr[1]<0.05), (d)=>{if (d[0]>0) d[0] = prime_annotation [d[0]-1]; else d [0] = \"Overall\"; return d;})};});\n s = _.sortBy (s, (d)=>d.p);\n let tests = summary_json[segment_id].map.length;\n _.each (s, (d,i)=> {\n d.q = Math.min (1,d.p * (tests/(i+1)));\n });\n return _.sortBy (s, (d)=>d.site);\n }","pinned":false,"hidden":false,"mode":"ojs"},{"id":798,"value":"negative_sites = {\n let s = _.map (_.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=>s[1].bFEL.p<=0.05 && s[1].bFEL.a > s[1].bFEL.b), (d)=>{return {'coordinate' : +d[0],'p' : d[1].bFEL.p,'meme_weight' : d[1].bMEME[\"w+\"],'gene': d[1].G, 'site' : d[1].S, 'alpha' : d[1].bFEL.a,'beta': \n d[1].bFEL.b};});\n s = _.sortBy (s, (d)=>d.p);\n let tests = summary_json[segment_id].map.length;\n _.each (s, (d,i)=> {\n d.q = Math.min (1,d.p * (tests/(i+1)));\n });\n return _.sortBy (s, (d)=>d.site);\n }","pinned":false,"hidden":false,"mode":"ojs"},{"id":2511,"value":"diff_sites = _.map (_.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=> Math.abs(s[1].bCFEL.pp)<=0.1), (d)=>[+d[0], d[1].bCFEL.a, d[1].bCFEL.b.background, d[1].bCFEL.b.Foreground, d[1].bCFEL.p.overall, d[1].S, d[1].G, report_ratio (d[1].bCFEL.b.background,d[1].bCFEL.b.Foreground),d[1].bCFEL.q])","pinned":false,"hidden":false,"mode":"ojs"},{"id":2552,"value":"directional_sites = _.map (_.map (_.filter (_.map (annotation_json, (v,k)=>[k,v]), (s)=> _.some (s[1].fade, (dd)=>dd.BF >= 100)), (d)=>[+d[0], d[1].fade, site2alignment[d[0]]]), (d)=>[d[0], _.map (_.filter (_.toPairs (d[1]), (r)=>r[1].BF >= 100), (d)=>d[0]).join (\"\"), d[2], annotation_json[d[0]].G, annotation_json[d[0]].S])","pinned":false,"hidden":false,"mode":"ojs"},{"id":2084,"value":"cfel_sites = {\n let result = [];\n _.each (_.chain (annotation_json).map ((d,k)=>[k,d]).filter ((d)=>d[1].bCFEL.pp > 0 && d[1].bCFEL.pp <= 0.05).value (), ((d)=> { _.each (d[1].bCFEL.p,(v,p)=>{\n if (v <= 0.05) {\n result.push ({'site' : d[0], 'type' : p, 'p' : v});\n }\n })}));\n return result;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2078,"value":"site_report = annotation_json [site2view]\n ","pinned":false,"hidden":false,"mode":"ojs"},{"id":2339,"value":"freq_report = (freqs)=> {\n return _.map (_.sortBy (_.map (freqs, (f,a)=>[a,f]), (d)=>-d[1]), (d)=> d[0] + \"_{\" + d[1] + \"}\").join (\" \");\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2354,"value":"cfel_site_report = (d)=> {\n const site_data = annotation_json[d][\"bCFEL\"];\n const spc = {\n 'Reference' : 'background',\n };\n spc[cladeName] = 'Foreground';\n \n return \"p-value = \" + float_format(site_data.p.overall) + \"

\" + _.map (species, (sp)=>\"\"). join (\"\") + \"

Branch group	ω
\" + sp + \"	\" + report_ratio (site_data.a, site_data.b[spc[sp]]) + \"

\";\n}\n\n","pinned":false,"hidden":false,"mode":"ojs"},{"id":2909,"value":"fade_site_report = (d)=> {\n const site_data = _.filter (_.toPairs (annotation_json[d][\"fade\"]), (d)=>d[1].BF >= 100);\n if (site_data.length) {\n return \"\" + _.map (site_data, (sp)=>\"\"). join (\"\") + \"

Target residue	Bias	Bayes Factor
\" + sp[0] + \"	\" +float_format (sp[1].rate) + \"	\" +float_format (sp[1].BF) + \"

\";\n }\n return \" No evidence of directional selection\";\n \n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2968,"value":"prime_site_report = (d)=> {\n const site_data = _.filter (annotation_json[d][\"prime\"][\"p\"], (d)=>d <= 0.05);\n if (site_data.length) {\n return \"\\n\" + _.map (annotation_json[d][\"prime\"][\"lambda\"], (sp,i)=>\"\"). join (\"\\n\") + \"

Property	λ	p-value importance
\" + summary_json[segment_id][\"prime-properties\"][i] + \"	\" +float_format (sp) + \"	\" +float_format (annotation_json[d][\"prime\"][\"p\"][i]) + \"

Omnibus importance test p = \" + float_format (annotation_json[d][\"prime\"][\"p\"][5]) + \"\";\n }\n return \"No evidence of property importance selection\";\n \n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2812,"value":"coevolve_sites =_.flatten (_.map (_.map (summary_json, (sd,si)=> [si,_.filter (sd[\"bgm\"], (d)=>d[4]>=0.5)]), (sd)=> {\n return _.map (sd[1], (d)=> {\n let dd = _.clone (d);\n let s1 = summary_json[sd[0]].map[d[0]-1];\n let s2 = summary_json[sd[0]].map[d[1]-1];\n dd.push (s1); dd.push (s2);\n dd.push (annotation_json[s1].G);\n dd.push (annotation_json[s1].S);\n dd.push (annotation_json[s2].S);\n return dd;\n })\n}))","pinned":false,"hidden":false,"mode":"ojs"},{"id":2886,"value":"subsByBranch = {\n let byBranch = {};\n _.each (summary_json[segment_id].subs, (d,k)=> {\n _.each (d, (state, branch)=> {\n if (state != \"---\") {\n if ((branch in byBranch) == false) {\n byBranch [branch] = [];\n }\n byBranch [branch].push (annotation_json[k].G + \"/\" + annotation_json[k].S);\n }\n });\n });\n return byBranch;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":2956,"value":"polymorphic_sites = _.chain (annotation_json).toPairs ().map ((d)=>[d[0], _.filter (d[1].aa ? _.toPairs(d[1].aa[cladeName]) : [], (r)=> r[0] != '-')]).filter ((d)=>d[1].length > 1).value()\n","pinned":false,"hidden":false,"mode":"ojs"},{"id":3079,"value":"entropy = (array)=> {\n const nonGap = _.filter (_.toPairs (array), (d)=>d[0] != '-');\n let N = d3.sum (nonGap, (d)=>d[1]);\n const log2 = Math.log (2);\n return -d3.sum (_.map (nonGap, (d)=>d[1]/N * Math.log (d[1]/N) / log2));\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":629,"value":"gene_coordinates = _.map ([\n //[266,'ORF1a',13483],\n //[13471, 'ORF1b',21555],\n [21563,'S',25385],\n /*[25393,'ORF3a',26220],\n [26245,'E',26472],\n [26523,'M',27191],\n [27202,'ORF6',27387],\n [27394,'ORF7a',27759],\n [27756,'ORF7b',27887],\n [27894,'ORF8',28259],\n [28274,'N',29533],\n [29558,'ORF10',29674]*/\n], (d,i)=>{\n d.push (i);\n return d;\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":1598,"value":"name_fragment = (n)=>{ \n let pieces = n.split ('_');\n if (pieces.length > 3) {\n return pieces[1]+\"/\"+pieces[2];\n }\n return pieces[1];\n};","pinned":false,"hidden":false,"mode":"ojs"},{"id":681,"value":"summary_json = analysis_info.s","pinned":false,"hidden":false,"mode":"ojs"},{"id":3388,"value":"has_full_meme = _.some (annotation_json, (d)=>\"lMEME\" in d)","pinned":false,"hidden":false,"mode":"ojs"},{"id":754,"value":"annotation_json = analysis_info.a","pinned":false,"hidden":false,"mode":"ojs"},{"id":1943,"value":"import { legend, swatches } from \"@d3/color-legend\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":2060,"value":"import {translation_table} from \"@spond/usual-vs-unusual-mutation-analyses\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":3435,"value":"import {a,r} from \"@stephenshank/alignment-js-in-obervablehq\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":3448,"value":"React = r('react')","pinned":false,"hidden":false,"mode":"ojs"},{"id":3451,"value":"ReactDOM = r('react-dom')","pinned":false,"hidden":false,"mode":"ojs"},{"id":3604,"value":"translation_table_gap = {\n let tt = translation_table;\n tt['---'] = '-';\n tt['NNN'] = '-';\n return tt;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":3573,"value":"translate_ambiguous_codon_gap = (c)=> {\n if (c in translation_table_gap) {\n return translation_table_gap[c];\n \n [c]; }\n \n return '-';\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":3549,"value":"$3b","pinned":false,"hidden":false,"mode":"ojs"},{"id":3674,"value":"html`\n\n`","pinned":false,"hidden":false,"mode":"ojs"}],"files":"$W3c","stdlib":"1","titling":"auto"}