29:null 2a:["$","title",null,{"children":"Evidence of natural selection history operating on SARS-CoV-2 genomes enabled by data from | Sergei Pond | Observable"}] 2f:T74d,

Analysis details

We regularly download and curate whole-genome data from GISAID. These data are passed through a SARS-CoV-2 analysis pipeline, which has not been published as a standalone tool, but has been used in a number of publications, including [1,2,3]. All sequences are partitoned into three-month intervals (by sampling dates) and subjected to a series of selection analyses. This notebook presents a temporal evolutionary history of selected sites, as characterized by the [FEL method]. During a given time interval, a site can be

Positively selected: natural selection may be promoting diversification (changes to different amino-acids) at this site.
Negatively selected: natural selection may be suppressing amino-acid variation at this site; the site is therefore evolutionary conserved at the protein level.
Evolving neutrally: all other cases; this includes cases where the FEL method lacks statistical power.

When a site is identified as evolving non-neutrally, a p-value from the likelihood ratio test is used to assess significance. These are reported in the plot. Note that p-values are not directly comparable across timepoints, because of different sample sizes and other factors.

30:T69e,main_view = vegalite({ "title": null, data: {values: forPlot}, transform: [{"calculate": "-log(datum.p)/log(10)", "as" : "psize"}], width : 700, layer: [ { "mark": {"type": "circle", "opacity" : 0.5, "stroke": "black", "strokeWidth": 1, size : 40, tooltip : true}, "encoding": { "x": {field: "to", timeUnit: "yearmonth", type: "temporal", scale: {nice: true, padding : 0.5, domain : date_range_obj}, axis: {"title": "Analysis using data from the preceding 3-month period", titleFontSize : 14, grid : false, "labelFontSize" : 12, labelAngle : 45}}, tooltip : [ {"field": "loc", "type": "ordinal", "title": "Site"}, {"field": "to", "type": "temporal", "title": "Analysis date"}, {"field": "p", "type": "quantitative", "title": "P-value", "format" : ".2g"}, {"field" : "seqs", "type": "quantitative", "title": "Repr. sequences used in analysis"} ], "y": {"sort": {"field" : "sorter"}, "field": "label", "type": "nominal", axis: { "titleFontSize" : 14, "labelFontSize" : 14, "grid" : false, 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(["nsp2/85","ORF1ab/1655","ORF1ab/3353","S/80","S/215","S/484","S/501","S/701","ORF3a/57","ORF3a/171","E/71","N/205","22280","11287"]), "gamma (P.1)" : pad_array (["733","2749","ORF1a/1118","ORF1a/1795","11287","12778","13860","S/20","S/26","S/417","S/484","S/501","S/1027","ORF8/92","N/80"]), "delta (B.1.617.2)" : pad_array (["S/19","S/142","S/452","S/478","S/681","S/950","ORF3a/26","M/82","ORF7a/82","ORF7a/120","N/63","N/203","N/377"]), "mu (B.1.621)" : pad_array (["3037","ORF1a/1055","ORF1a/1538","6037","ORF1a/3255","ORF1a/3729","13057","ORF1b/314","ORF1b/1342","18877","19035","20148","S/95","S/145","S/346","S/484","S/501","S/614","S/681","S/950","ORF3a/57","ORF8/11","ORF8/38","ORF8/67","N/205"]), "omicron (B.1.1.529)" : pad_array (["NSP3/38", "NSP3/1069", "NSP3/1266", "NSP3/1892","NSP4/492","3C/132","NSP6/189","RDRP/323","exonuclease/42","S/67","S/95","S/142","S/212","S/339","S/371","S/373","S/375","S/417","S/440","S/446","S/477","S/478","S/484","S/493","S/496","S/498","S/501","S/505","S/547","S/614","S/655","S/679","S/681","S/764","S/796","S/856","S/954","S/969","S/981","E/9","M/3","M/19","M/63","N/13","N/203","N/204"]), "Positive selected recent 3 intervals" : pad_array(recent_site_list), "Negatively selected recent 3 intervals" : pad_array(recent_site_listN) })32:[] 2d:{"id":"af4f57560028bdc1","slug":"sars-cov-2-selected-sites","title":"Evidence of natural selection history operating on SARS-CoV-2 genomes enabled by data from ","thumbnail":"f9078956df106812610c04e18a6e619dbdc80c2fc6aebd52b4fc507c290b25df","access_level":"public","create_time":"$D2021-09-08T17:37:32.441Z","update_time":"$D2022-03-02T21:36:30.616Z","view_time":null,"first_public_time":"$D2021-09-08T20:57:11.015Z","has_unpublished_edits":null,"fork":{"id":"a0884828911c29f9","slug":"sc2-temporal-selection-trends","title":"Temporal evolution of selective pressures on SARS-CoV-2 genes","owner":{"id":"9bf992815a7b66f2","login":"spond","name":"Sergei Pond"}},"stars":0,"starred":false,"owner":{"type":"team","id":"9bf992815a7b66f2","login":"spond","name":"Sergei Pond","avatar_url":"https://avatars-next.observableusercontent.com/23c8c466a3ef27f1444c95a9ed8e52bcf08888403b6d4efbd039319b0761c13d","tier":"starter_2024"},"version":1649,"publish_version":1649,"role":null,"authored":false,"authors":[{"type":"individual","id":"f439ea11e6786e12","login":"spond","name":"Sergei Pond","avatar_url":"https://avatars-next.observableusercontent.com/23c8c466a3ef27f1444c95a9ed8e52bcf08888403b6d4efbd039319b0761c13d","tier":null}],"members":[{"type":"individual","id":"f439ea11e6786e12","login":"spond","name":"Sergei Pond","avatar_url":"https://avatars-next.observableusercontent.com/23c8c466a3ef27f1444c95a9ed8e52bcf08888403b6d4efbd039319b0761c13d","tier":null,"role":"editor"}],"comments":[],"custom_thumbnail":false,"trashed":false,"lapsed":null,"subscribed":null,"forks":6,"collection":null,"type":"notebook","body":{"title":"Evidence of natural selection history operating on SARS-CoV-2 genomes enabled by data from ","cells":[{"id":0,"value":"md`# Evidence of natural selection history operating on SARS-CoV-2 genomes enabled by data from $\"gisaid-logo\"$
`","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1137,"value":"For a given set of SARS-CoV-2 genomic sites, see when and how natural selection operated on them, through a series of 3-month overlapping intervals going back to the beginning of the pandemic. The earliest intervals ends in _${date_range[0]}_ and the latest - in _${date_range[1]}_. [Download .csv data](https://github.com/spond/SARS-CoV-2-variation)","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1123,"value":"$2f","pinned":false,"hidden":false,"mode":"html","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1192,"value":"viewof preset = select ({\n options : sitelist ? [\"Supplied as arguments\"] : _.keys (preset_mapping),\n description: \"Select one of the presets for sites to display\",\n value: \"omicron (B.1.1.529)\"\n})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1170,"value":"viewof sites = multiAutoSelect ({\n options : sitelist ? [] : _.uniq (_.map (selectable_sites, (d)=>{let p = d.split (\"/\"); return \"Codon \" + p[0] + \"/\" + Math.floor (p[1])})),\n title: \"Track the following mutations\",\n value : sitelist ? _.map (sitelist.split (/[ ,]/), (d)=>\"Site \" + d) : preset_mapping[preset]\n})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1152,"value":"**Figure 1.** Evolutionary trajectories of **${sites.length}** selected sites. If a site was found to be positively (negatively) selected during a specific time period, a bubble will be drawn at a corresponding point on the plot. The area of the bubble is scaled as -log₁₀ (p), where p is the p-value of the FEL likelihood ratio test. Larger bubbles correspond to smaller p-values; p-values are not directly comparable between different time windows and different genes due to differences in sample sizes and other factors. The x-axis shows the **endpoint** of the time-window; e.g., Mar 30th 2021 will correspond to the analysis performed with the data from Jan 01 2021 to Mar 30th 2021.","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":588,"value":"$30","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1378,"value":"md`**Table 1.** Explore the underlying data`","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1368,"value":"viewof wrangled = Wrangler(siteHistory)","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":5,"value":"md`### Libraries and data`","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":9,"value":"d3 = require(\"d3@6\")","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1194,"value":"import {select} from \"@jashkenas/inputs\"","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":12,"value":"vegalite = require (\"vega-embed\")","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":15,"value":"_ = require (\"lodash\")","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":22,"value":"import {gene_coordinates} from \"@spond/revised-sars-cov-2-analytics-page\"","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1365,"value":"import {Wrangler, op} from \"@observablehq/data-wrangler\"","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":692,"value":"site_equiv = _.groupBy (_.toPairs (jsonCodonLookup), (d)=>d[1])","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":49,"value":"import {jsonCodonLookup} from \"@spond/sars_cov_2_sites\"","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":58,"value":"import {multiAutoSelect} from \"@spond/untitled/3\"","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1209,"value":"$31","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1218,"value":"siteList = parseSiteList (_.map (sites, (d)=>d.split (\" \")[1]))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1433,"value":"unique_times = _.sortBy (_.keys(_.countBy (siteHistory, (d)=>d.to.getTime())))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1454,"value":"last3 = _.map (unique_times.slice (-3), (d)=>+d)","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1439,"value":"all_times = _.toPairs (_.groupBy (_.filter (siteHistory, (d)=>d.alpha < d.beta && d.p < 0.01), (d)=>d.loc))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1550,"value":"all_timesN = _.toPairs (_.groupBy (_.filter (siteHistory, (d)=>d.alpha > d.beta && d.p < 0.01), (d)=>d.loc))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1445,"value":"recent_site_list = _.map (_.filter (all_times, (d)=>_.intersection(last3,_.map (d[1], (c)=>c.to.getTime())).length == 3), (d)=>d[0])","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1553,"value":"recent_site_listN = _.map (_.filter (all_timesN, (d)=>_.intersection(last3,_.map (d[1], (c)=>c.to.getTime())).length == 3), (d)=>d[0])","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1327,"value":"dr = d3.extent (siteHistory, (d)=>d.to)","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1402,"value":"pad_array = (arr)=>_.map (arr, (d)=>\"Site \" + d.toUpperCase())","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1477,"value":"selectable_sites = _.keys(jsonCodonLookup)","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1233,"value":"date_range = _.map (dr, (d)=>d3.timeFormat (\"%B %Y\")(d))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1349,"value":"date_range_obj = _.map (dr, (d)=>({'year' : d.getFullYear(), 'month': 1+d.getMonth(), 'day' : d.getDate() + 1}))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":46,"value":"siteHistory = {\n let raw_data = await d3.csv (\"https://raw.githubusercontent.com/spond/SARS-CoV-2-variation/master/windowed-sites-fel-current.json\", d3.autoType);\n //let raw_data = d3.csvParse (await FileAttachment(\"windowed-sites-fel-current@1.txt\").text(), d3.autoType);\n _.each (raw_data, (s)=>{\n s.loc = s.gene.toUpperCase() + \"/\" + s.site;\n /*if (s.loc in siteList[1]) {\n s.label = siteList[1][s.loc]; \n } (else { */\n s.label = s.loc;\n //}\n s.sorter = parseInt(jsonCodonLookup[s.loc]);\n s.p = Math.max (s.p, 1e-16);\n \n });\n return raw_data;\n}","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1382,"value":"forPlot = {\n let selected = _.filter (siteHistory, (d)=>siteList[0].has (d.loc));\n let ss = _.countBy (selected, (d)=>d.loc);\n _.each ([...siteList[0]], (s)=> {\n if (! (s in ss)) {\n selected.push ({\"label\" : s, \"sorter\" : parseInt(jsonCodonLookup[s])})\n }\n });\n return selected;\n}","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1259,"value":"nucToCodons = _.chain (_.toPairs (jsonCodonLookup)).groupBy ((d)=>d[1]).mapValues ((d)=>_.map (d, (c)=>c[0])).value()","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":596,"value":"parseSiteList = (site_list) => {\n let labels = {};\n site_list = _.map (site_list, (d)=>d.split (\"/\"));\n \n let sites = new Set (_.map (site_list, (d)=>{\n if (+d == d) {\n for (let i = d; i > d-3; i--) {\n if (i in nucToCodons) {\n d = nucToCodons[i][0].split (\"/\");\n break;\n }\n }\n \n }\n if (d[0].substr (0,4) == \"ORF1\") {\n let eq = null;\n _.each (site_equiv[jsonCodonLookup [d[0]+\"/\"+d[1]]], (tr)=> {\n if (tr[0].substr (0,4) != \"ORF1\") {\n eq = tr[0];\n labels[eq] = d[0] + \"/\" + d[1];\n }\n });\n return eq;\n }\n return d[0] + \"/\" + d[1];\n}));\n return [sites, labels]\n}","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1341,"value":"params = new URLSearchParams(location.search)","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":1344,"value":"sitelist = params.get(\"sites\") ? params.get(\"sites\").toUpperCase() : null","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"}],"files":"$W32","stdlib":"1","titling":"auto"}} 2e:"$2d:body"