31:T540,vegalite ({ "$schema": "https://vega.github.io/schema/vega-lite/v4.json", "data": { "values": byVariant[variantToView] ? byVariant[variantToView] : [] }, "layer" : [ { "width": 800, "height": 50, "transform":[{ "density": "AF", //"bandwidth": 0.01 }], "mark": {type: "area", "opacity" : 0.2, tooltip : true, line : true}, "encoding": { "x": { "field": "value", "grid" : null, "title": "Allele Frequency", "type": "quantitative", "axis": {"grid": false} }, "y": { "field": "density", "type": "quantitative", "title" : "", "axis": {"grid": false} }, "color" : {"value" : "grey"}, } }, { "mark": {type: "tick", "opacity" : 0.5, tooltip : true, size : 10, thickness: 2}, "transform":[{ "calculate": "-0", "as": "placement" }], "encoding": { "x": { "field": "AF", "grid" : null, "title": "Allele Frequency", "type": "quantitative", "axis": {"grid": false} }, "y" : { "type": "quantitative", "field" : "placement" }, "color" : {"value" : "darkred"}, } }, ] }) 32:T966,genomicDist = vegalite ({ "$schema": "https://vega.github.io/schema/vega-lite/v4.json", "config" : { "bar": {continuousBandSize : 3} }, "data": { "values": colocation, }, "vconcat" : [ { "width": 800, "height" : 100, "selection": { "brush": {"type": "interval", "encodings": ["x"]} }, "mark": {"type": "bar", "tooltip": {"content": "data"}, "filled": true, "clip" : true}, "encoding": { "y": { "field": "freq", "type": "quantitative", "axis" : {"grid" : false, "title" : "Variant frequency", "orient" : "left"}, "scale" : {"type" : "sqrt", domain: [0,1]} }, "x" : { "field": "coord", "type": "quantitative", "axis" : {"grid" : false, "title" : "Genomic Position"}, "scale" : {zero:false, domainMin: 1, domainMax : 29903} }, "color" : { "field" : measure, "type" : "quantitative", "condition": { "test": "datum['Variant'] == '" + variantToView + "'", "value": "darkred" }, "scale" : {"domain" : [0,1]} } } }, { "width": 800, "height" : 100, "selection": { "brush": {"type": "interval", "encodings": ["x"]} }, "mark": {"type": "bar", "tooltip": {"content": "data"}, "filled": true, "clip" : true}, "encoding": { "y": { "field": "freq", "type": "quantitative", "axis" : {"grid" : false, "title" : "Variant frequency", "orient" : "left"}, "scale" : {"type" : "sqrt", domain: [0,1]} }, "x" : { "field": "coord", "type": "quantitative", "axis" : {"grid" : false, "title" : "Genomic Position"}, "scale" : {"domain": {"selection": "brush"}, zero:false, domainMin: 1, domainMax : 29903} }, "color" : { "condition": { "test": "datum['Variant'] == '" + variantToView + "'", "value": "darkred" }, "field" : measure, "type" : "quantitative", "scale" : {"domain" : [0,1]} } } //"shape": {"field": "species", "type": "nominal"} }] //"resolve": {"scale": {"y": "independent"}} })33:[] 2f:{"title":"Exploring SARS-CoV-2 intrahost variation (individual variants)","cells":[{"id":0,"value":"md`# Exploring SARS-CoV-2 intrahost variation (individual variants)`","pinned":false,"hidden":false,"mode":"ojs"},{"id":858,"value":"table1label = md`**Table 1**. Summary of all allelic variants found in the **${N.samples}** samples. Mean AF : mean frequency of the variant in samples where it found; COV AF : mean frequency of the variant in samples where it found `","pinned":false,"hidden":false,"mode":"ojs"},{"id":835,"value":"viewof table1 = Inputs.table (_.sortBy (_.map (byVariant, (d,k)=>{\n let c = cov (_.map (d, (dd)=>dd.AF));\n return ({'AV' : k, 'Samples' : d.length, 'Fraction' : d.length / N.samples, 'type' : map2key (d[0].EFFECT), 'Mean AF' : c[0], 'COV AF' : c[2]});\n }), (d)=>-d.Samples), { \n rows : 15\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":149,"value":"viewof variantToView = autoSelect({\n options: _.keys (byVariant),\n title: \"Select an intra-host variant to explore further\"\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":564,"value":"md`Variant ${variantToView} is found in **${(byVariant[variantToView] ? byVariant[variantToView] : []).length}/${N.samples}** samples. ${variant_summary}\n\nSee what is happening at this variant in global data`","pinned":false,"hidden":false,"mode":"ojs"},{"id":39,"value":"md`**Figure 1.** Distribution of allele frequencies for ${variantToView} and its smoothed kernel density`","pinned":false,"hidden":false,"mode":"ojs"},{"id":63,"value":"$31","pinned":false,"hidden":false,"mode":"ojs"},{"id":780,"value":"viewof measure = radio({\n title: 'Use this measure of association',\n options: [\n { label: 'Linkage disequilbrium (r2)', value: 'r2' },\n { label: 'Cosine Similarity', value: 'cosine' },\n ],\n value: 'r2'\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":695,"value":"md`**Figure 2.** Frequency of finding other variants in the **${(byVariant[variantToView] ? byVariant[variantToView] : []).length}** samples where ${variantToView} is present (shown in dark red). Other variants are colored by their ${measure} value with ${variantToView} computed over the entire sample`","pinned":false,"hidden":false,"mode":"ojs"},{"id":675,"value":"$32","pinned":false,"hidden":false,"mode":"ojs"},{"id":420,"value":"md`** Table 1 **. Variants that have ${measure}≥0.7`","pinned":false,"hidden":false,"mode":"ojs"},{"id":723,"value":"table (_.filter (colocation, (d)=>d[measure] >= 0.7),\n {\n limit: 5000,\n enableCSVDownload: true,\n sort: true,\n enableFilter: false,\n columns: [\n \n {\n key: 'Variant',\n name: 'Variant'\n },\n {\n key: 'f1',\n name: 'Freq (' + variantToView + ')',\n render: (val)=>val.toFixed (3)\n },\n {\n key: 'f2',\n name: 'Freq (SNP2)',\n render: (val)=>val.toFixed (3)\n },\n {\n key: 'f12',\n name: 'Freq (Pair)',\n render: (val)=>val.toFixed (3)\n },\n {\n key: 'r2',\n name: 'LD r2',\n render: (val)=>val.toFixed (3)\n },\n {\n key: 'cosine',\n name: 'Cosine Similarity',\n render: (val)=>val.toFixed (3)\n }\n ]\n});","pinned":false,"hidden":false,"mode":"ojs"},{"id":742,"value":"md`### Data`","pinned":false,"hidden":false,"mode":"ojs"},{"id":21,"value":"variantTable = _.filter (await obtainSourceData(), (d)=>d.FILTER == \"PASS\" || (\"FILTER\" in d == false))","pinned":false,"hidden":false,"mode":"ojs"},{"id":28,"value":"byVariant = _.groupBy (variantTable, (v)=>variantKey(v))","pinned":false,"hidden":false,"mode":"ojs"},{"id":173,"value":"equiv_map = {\n return {\n 'SYNONYMOUS_CODING' : 'Synonymous',\n 'NON_SYNONYMOUS_CODING' : 'Non-synonymous',\n '.' : 'Non-coding',\n 'STOP_GAINED' : 'Stop'\n }\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":620,"value":"N = {\n return {\n samples : _.size (bySample) \n }\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":615,"value":"bySample = _.groupBy (variantTable, (d)=>d.Sample)","pinned":false,"hidden":false,"mode":"ojs"},{"id":178,"value":"map2key = (d)=> {return d in equiv_map ? equiv_map[d] : \"Indel\"};","pinned":false,"hidden":false,"mode":"ojs"},{"id":749,"value":"orderedSampleNames = _.fromPairs (_.map (_.sortBy (_.keys (bySample)), (d,i)=>[d,i]))","pinned":false,"hidden":false,"mode":"ojs"},{"id":634,"value":"colocation = {\n let otherVariants = {};\n if (byVariant[variantToView]) {\n let F = variantFreqBySample (variantToView);\n _.each (byVariant[variantToView], (s)=> {\n _.each (bySample[s.Sample], (v)=> {\n let vk = variantKey (v);\n //if (vk != variantToView) {\n otherVariants[vk] = 1 + (otherVariants[vk] || 0);\n //}\n });\n });\n return _.map (_.toPairs (otherVariants), (d)=> {\n return _.extend ({'Variant' : d[0], 'coord' : +d[0].split ('|')[0], 'freq' : d[1]/byVariant[variantToView].length, 'cosine' : cosine_sim (F, variantFreqBySample (d[0]))}, \n pair_frequency (variantFrequencies[variantToView], \n variantFrequencies[d[0]],\n d[1]/N.samples))});\n }\n return [];\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":629,"value":"variantFrequencies = _.fromPairs(_.map (byVariant, (d,k)=>[k, _.size (d)/N.samples]))","pinned":false,"hidden":false,"mode":"ojs"},{"id":24,"value":"md`### Utility functions`","pinned":false,"hidden":false,"mode":"ojs"},{"id":577,"value":"variant_summary = {\n if (byVariant[variantToView]) {\n let afs = _.map (byVariant[variantToView], (d)=>d.AF);\n let info = cov (afs);\n return \"
Mean AF **\" + float_format (info[0]) + \"** (range \" + _.map (d3.extent (afs), (d)=>float_format (d)).join (\"-\") + \") CoV = **\" + float_format(info[2]) + \"**. \"\n + \"
This variant is : \" + map2key (byVariant[variantToView][0].EFFECT) + \".\"\n + (byVariant[variantToView][0].CODON != '.' ? \"
Codon change: \" + byVariant[variantToView][0].CODON + \".\" : \"\")\n + (byVariant[variantToView][0].AA != '.' ? \"
Amino-acid at site: \" + byVariant[variantToView][0].TRID+ \"/\" + byVariant[variantToView][0].AA + \".\" : \"\")\n\n \n ;\n }\n return \"_Nothing selected_\";\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":745,"value":"cosine_sim = (d1,d2)=> {\n let sp = 0., n1 = 0., n2 = .0;\n \n for (let i = 0; i < d1.length; i++) {\n sp += d1[i]*d2[i];\n n1 += d1[i]*d1[i];\n n2 += d2[i]*d2[i];\n }\n return sp / Math.sqrt (n1*n2);\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":652,"value":"pair_frequency = (f1, f2, f12) => {\n \n let D = f12-f1*f2;\n \n return {'f1' : f1,\n 'f2' :f2,\n 'f12': f12,\n 'r2' : D*D/(f1*(1-f1)*f2*(1-f2)),\n 'Dprime' : D / (D > 0 ? Math.min (f1*(1-f2),f2*(1-f1)) : Math.max (-f1*f2, -(1-f1)*(1-f2)))};\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":748,"value":"variantFreqBySample = (v)=> {\n let f = new Array (N.samples);\n for (let i = 0; i < N.samples; i++) f[i] = 0.;\n _.each (byVariant[v], (d)=>f[orderedSampleNames[d.Sample]] = d.AF);\n return f;\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":476,"value":"generate_summary_stats = (counts)=> {\n return _.map (_.groupBy (counts, (d)=>d.kind), (c,k)=> {\n return {'kind' : k, \n 'mean' : d3.mean (c, (cc)=>cc.count), \n 'median' : d3.median (c, (cc)=>cc.count), \n 'range' : [d3.min (c, (cc)=>cc.count),d3.max (c, (cc)=>cc.count)],\n 'IQR' : [d3.quantile (c, 0.25, (cc)=>cc.count),d3.quantile (c, 0.75, (cc)=>cc.count)]\n };\n })\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":124,"value":"variantKey = (d)=> {return \"\" + d.POS + \"|\" + d.REF + \"|\" + d.ALT + \" \" + d.TRID + \" \" + d.AA}","pinned":false,"hidden":false,"mode":"ojs"},{"id":36,"value":"collision_entropy = (dist)=> {\n return -Math.log (dist, (sum,p)=> sum + p*p);\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":251,"value":"cov = (freqs)=> {\n let sum = 0,\n sum2 = 0,\n n = freqs.length;\n \n _.each (freqs, (f)=> {sum += f; sum2 += f*f;});\n let mean = sum/n;\n let variance = sum2/n - mean*mean;\n return [mean,variance,Math.sqrt (variance)/mean,n];\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":439,"value":"float_format = d3.format (\".2f\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":485,"value":"frac_format = d3.format (\".2p\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":5,"value":"md`### Libraries/Modules`","pinned":false,"hidden":false,"mode":"ojs"},{"id":12,"value":"d3 = require (\"d3\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":15,"value":"_ = require (\"lodash\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":18,"value":"vegalite = require (\"vega-embed\")","pinned":false,"hidden":false,"mode":"ojs"},{"id":134,"value":"import {autoSelect, radio} from \"@jashkenas/inputs\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":415,"value":"import {table} from \"@gampleman/table\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":717,"value":"import {multiAutoSelect} from \"@spond/untitled/3\"","pinned":false,"hidden":false,"mode":"ojs"},{"id":797,"value":"import {obtainSourceData} from \"@spond/exploring-sars-cov-2-intrahost-variation-descriptive\"","pinned":false,"hidden":false,"mode":"ojs"}],"files":"$W33","stdlib":"1","titling":"auto"}