32:T53d,vegalite ({ "$schema": "https://vega.github.io/schema/vega-lite/v4.json", "data": { "values": bySample[variantToView] ? bySample[variantToView] : [] }, "layer" : [ { "width": 800, "height": 80, "transform":[{ "density": "AF", //"bandwidth": 0.01 }], "mark": {type: "area", "opacity" : 0.2, tooltip : true, line : true}, "encoding": { "x": { "field": "value", "grid" : null, "title": "Allele Frequency", "type": "quantitative", "axis": {"grid": false} }, "y": { "field": "density", "type": "quantitative", "title" : "", "axis": {"grid": false} }, "color" : {"value" : "grey"}, } }, { "mark": {type: "tick", "opacity" : 0.5, tooltip : true, size : 10, thickness: 2}, "transform":[{ "calculate": "-0", "as": "placement" }], "encoding": { "x": { "field": "AF", "grid" : null, "title": "Allele Frequency", "type": "quantitative", "axis": {"grid": false} }, "y" : { "type": "quantitative", "field" : "placement" }, "color" : {"field" : "EFFECT"}, } }, ] }) 33:T80b,genomicDist = vegalite ({ "$schema": "https://vega.github.io/schema/vega-lite/v4.json", "config" : { "bar": {continuousBandSize : 3} }, "data": { "values": bySample [variantToView], }, "vconcat" : [ { "width": 800, "height" : 100, "selection": { "brush": {"type": "interval", "encodings": ["x"]} }, "mark": {"type": "bar", "tooltip": {"content": "data"}, "filled": true, "clip" : true}, "encoding": { "y": { "field": "AF", "type": "quantitative", "axis" : {"grid" : false, "title" : "Variant frequency", "orient" : "left"}, "scale" : {"type" : "linear", domain: [0,1]} }, "x" : { "field": "POS", "type": "quantitative", "axis" : {"grid" : false, "title" : "Genomic Position"}, "scale" : {zero:false, domainMin: 1, domainMax : 29903} }, "color" : { "field" : "cluster", "type" : "nominal", } } }, { "width": 800, "height" : 100, "selection": { "brush": {"type": "interval", "encodings": ["x"]} }, "mark": {"type": "bar", "tooltip": {"content": "data"}, "filled": true, "clip" : true}, "encoding": { "y": { "field": "AF", "type": "quantitative", "axis" : {"grid" : false, "title" : "Variant frequency", "orient" : "left"}, "scale" : {"type" : "linear", domain: [0,1]} }, "x" : { "field": "POS", "type": "quantitative", "axis" : {"grid" : false, "title" : "Genomic Position"}, "scale" : {"domain": {"selection": "brush"}, zero:false, domainMin: 1, domainMax : 29903} }, "color" : { "field" : "cluster", "type" : "nominal", } } //"shape": {"field": "species", "type": "nominal"} }] //"resolve": {"scale": {"y": "independent"}} })34:[] 30:{"title":"Exploring SARS-CoV-2 intrahost variation (individual samples)","cells":[{"id":0,"value":"md`# Exploring SARS-CoV-2 intrahost variation (individual samples)`","pinned":false,"hidden":false,"mode":"ojs"},{"id":1131,"value":"og.markdown_banner()","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; ≥50%, 10-50%, <10% : number of AVs within this AF range in the sample. Subpopulations counts the number of AF clusters with more than one AV based on OPTICS clustering.`","pinned":false,"hidden":false,"mode":"ojs"},{"id":835,"value":"viewof table1 = Inputs.table (_.sortBy (_.map (bySample, (d,k)=>{\n let c = cov (_.map (d, (dd)=>dd.AF));\n let vc = _.countBy (_.map (d, (dd)=>dd.AF >= 0.5 ? \"≥50%\" : (dd.AF >= 0.1 ? \"10-50%\" : '<10%')));\n return ({'Sample' : k, 'AVs' : d.length, 'Mean AF' : c[0], '≥50%' : vc[\"≥50%\"], '10-50%' : vc[\"10-50%\"], '<10%' : vc[\"<10%\"], 'Subpopulations' : _.filter (fClusters[k], (d)=>d.length > 1).length});\n }), (d)=>-d.AVs), { \n rows : 15\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":149,"value":"viewof variantToView = autoSelect({\n options: _.keys (bySample),\n title: \"Select a sample to expore further\",\n placeholder: \"SRA accession (default SRR14460618)\",\n value: \"SRR14460618\"\n})","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":"$32","pinned":false,"hidden":false,"mode":"ojs"},{"id":695,"value":"md`**Figure 2.** Allelic variants found in ${variantToView} and their inferred population clusters`","pinned":false,"hidden":false,"mode":"ojs"},{"id":675,"value":"$33","pinned":false,"hidden":false,"mode":"ojs"},{"id":962,"value":"viewof table2 = Inputs.table (_.sortBy (_.map (bySample[variantToView], (d)=>{\n return (_.extend ({'Position' : d.POS, 'AV' : variantKey(d, true), 'AF' : d.AF, 'Cluster' : d.cluster}, annotate_variant(d)));\n }), (d)=>d.POS), { \n rows : 15,\n format : {\n 'HaploRelRank' : (d)=>d.toFixed (6)\n }\n})","pinned":false,"hidden":false,"mode":"ojs"},{"id":742,"value":"md`### Data`","pinned":false,"hidden":false,"mode":"ojs"},{"id":21,"value":"variantTable = _.filter (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":944,"value":"fClusters = {\n let c = {};\n _.each (bySample, (s,v)=> {\n c[v] = dbscan.run(_.map (s, (d)=>[d.AF]), 0.1, 2);\n _.each (c[v], (vv, ci)=> {\n if (vv.length > 1) {\n _.each (vv, (idx)=> {\n s[idx].cluster = ci + 1;\n });\n } else {\n s[vv[0]].cluster = null;\n }\n });\n })\n return c;\n}","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":629,"value":"variantFrequencies = _.fromPairs(_.map (byVariant, (d,k)=>[k, _.size (d)/N.samples]))","pinned":false,"hidden":false,"mode":"ojs"},{"id":1063,"value":"vegalite({\n \"data\": {\"values\": clade_cred},\n \"mark\": {type : \"point\", filled : true, size : 64, tooltip : {\"content\" : \"data\"}},\n \"width\" : 400,\n \"height\" : 400,\n \"encoding\": {\n \"x\": {\"field\": \"L\", \"type\": \"quantitative\", \"axis\" : {\"grid\" : false}},\n \"y\": {\"field\": \"F\", \"type\": \"quantitative\", \"axis\" : {\"grid\" : false}},\n \"color\": {\"field\": \"U\", \"type\": \"quantitative\",\"scale\": {\"scheme\": \"rainbow\"}},\n }\n})\n","pinned":false,"hidden":false,"mode":"ojs"},{"id":1049,"value":"clade_cred = {\n let byClade = {};\n _.each (variantAnnotation, (data, v)=> {\n let dc = data[\"Clade0.75\"];\n if (dc && dc.length) {\n _.each (dc.split (';'), (cl)=> {\n if (! (cl in byClade)) {\n byClade[cl] = [[],0];\n } \n byClade[cl][0].push (v);\n if (_.isNumber (data.Pred)) {\n byClade[cl][1] += (data.Pred < 1e-6 ? 1 : 0);\n } \n });\n }\n });\n return _.map (_.sortBy (_.toPairs (byClade), (d)=>-d[1][1]/d[1][0].length), (d)=> (\n { \n 'Clade' : d[0],\n 'L' : d[1][0].length,\n 'U' : d[1][1],\n 'F' : d[1][1]/d[1][0].length\n }));\n}","pinned":false,"hidden":false,"mode":"ojs"},{"id":1103,"value":"_.filter (variantAnnotation, (d)=>d.Coord == 17259)","pinned":false,"hidden":false,"mode":"ojs"},{"id":981,"value":"variantAnnotation = _.fromPairs (_.map (await d3.csv (\"https://raw.githubusercontent.com/spond/SARS-CoV-2-variation/master/variation/variant-annotation.csv\", d3.autoType), (d)=>[d.Coord + \"/\" + d.Codon,d]))","pinned":false,"hidden":false,"mode":"ojs"},{"id":24,"value":"md`### Utility functions`","pinned":false,"hidden":false,"mode":"ojs"},{"id":988,"value":"annotate_variant = (v)=> {\n if (v.CODON.length > 1) {\n let cdn = v.CODON.split ('/')[1].toUpperCase();\n for (let i = v.POS-1; i >= v.POS - 3; i--) {\n let tg = \"\" + i + \"/\" + cdn;\n if (tg in variantAnnotation) {\n let va = variantAnnotation[tg];\n return {\n 'Global Freq' : va['GlobalF'],\n 'Clades' : va['Clade0.75'] ? va['Clade0.75'].replace (/;/gi, ', ', true) : null,\n 'Predicted' : _.isNumber (va['Pred']) ? (va['Pred'] >= 0.001 ? 'Yes' : (va['Pred'] > 0 ? 'LF' : 'No')) : null,\n 'HaploRelRank' : _.isNumber (va['Haplo']) ? va['Haplo'] : '',\n 'LastSel' : va['LastSel']\n }\n }\n }\n }\n return {'Global Freq' : null, 'Clades' : null, 'Predicted' : null};\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, short)=> {return \"\" + (short ? \"\" : 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":913,"value":"dbscan = new clustering.OPTICS()","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":904,"value":"clustering = require('https://bundle.run/density-clustering@1.3.0')","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":1114,"value":"axios = require('axios');","pinned":true,"hidden":false,"mode":"ojs"},{"id":1116,"value":"obtainSourceData = {\n return d3.tsvParse(data.summary_tsv, d3.autoType);\n}","pinned":true,"hidden":false,"mode":"ojs"},{"id":1124,"value":"data = og.autofetcher()","pinned":false,"hidden":false,"mode":"ojs"},{"id":1127,"value":"og = new ObservableGalaxy()","pinned":true,"hidden":false,"mode":"ojs"},{"id":1122,"value":"import { ObservableGalaxy } from \"@stephenshank/the-observable-galaxy\";","pinned":true,"hidden":false,"mode":"ojs"}],"files":"$W34","stdlib":"1","titling":"auto"}