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Lamb","avatar_url":"https://avatars-next.observableusercontent.com/01b5f491b7dc6ccd2a81b4681d30c9693b427ea0f1022b2764d0156e67e53309","tier":null}],"members":[{"type":"individual","id":"1c0f023b5e4ac4b5","login":"kieran12lamb","name":"Kieran Lamb","avatar_url":"https://avatars-next.observableusercontent.com/01b5f491b7dc6ccd2a81b4681d30c9693b427ea0f1022b2764d0156e67e53309","tier":null,"role":"editor"},{"type":"team","id":"1157d8a0e7ace7c6","login":"cvr-bioinfo","name":"CVR Bioinformatics","avatar_url":"https://avatars-next.observableusercontent.com/022d43de01273d3d19941f51b9b2c412d919f4a74262d41e14c5379b08c7d5f2","tier":"pro_2024","role":"viewer"}],"comments":[],"custom_thumbnail":false,"trashed":false,"lapsed":null,"subscribed":null,"forks":0,"collection":null,"type":"notebook","body":{"title":"H655Y Mutation and Reversion","cells":[{"id":0,"value":"# H655Y Mutation and Reversion","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":179,"value":"The left hand structure (at the start of the gif) is the Wuhan-Hu-1 spike protein with the H655Y mutations added.\n\nThe right structure (at the start of the gif) is the BA.2.86 spike with the H655Y mutation removed. ","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":5,"value":"FileAttachment(\"movie.gif\").image()","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":185,"value":"Assuming the mutation has the same effect in Wuhan-Hu-1 as it does in BA.2.86, we would expect to see that the areas in red in the Wuhan-Hu-1 be blue in the BA.2.86 spike. \n\nThis is true for the below sites, although how much they change does vary:","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":212,"value":"common_affected_sites = wuhan.filter(d=>{if(d.change >=0.01){return d}}).concat(ba286.filter(d=>{if(d.change <=-0.01){return d}})).map(d=>d.pos).filter((e, i, a) => a.indexOf(e) !== i).concat(wuhan.filter(d=>{if(d.change <=-0.01){return d}}).concat(ba286.filter(d=>{if(d.change >=0.01){return d}})).map(d=>d.pos).filter((e, i, a) => a.indexOf(e) !== i))","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":267,"value":"A number of sites are not shared between the spikes, suggesting that the backbone has an effect on how the mutation affects these other sites. These sites are also below:","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":244,"value":"other_affected_sites = wuhan.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}).map(d=>{return d.pos}).concat(ba286.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}).map(d=>{return d.pos})).filter((e, i, a) => a.indexOf(e) !== i).filter(d=>{if(new Set(common_affected_sites).has(d)){return }else{return d}})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":292,"value":"The initial observations are that BA.2.86 does seem to affect different sites on a H655Y reversion than the Wuhan-Hu-1 spike does on a H655Y mutation. \n\nIn particular, position 651 looks to significantly prefer the H at position 655 in a BA.2.86 backbone (a probability change of 0.78 which is very large).\n\nIn a Wuhan-Hu-1 backbone it only slightly prefers the H (a change of 0.024).\n\nAlso, in the BA.2.86 backbone, we see some effect on furin cleavage site (683 and 684) positions which we don’t see in Wuhan-Hu-1.","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":294,"value":"## Plot settings\nI've provided some plotting options for the below scatter plots in case you prefer a different colour set. ","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":108,"value":"$31","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":285,"value":"## Wuhan-Hu-1 Affected sites\nEach point is a site affected by the H655Y mutation in the Wuhan-Hu-1 spike. The orange bars show the position of the Furin Clevage Site and the S2' cleavage site.","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":32,"value":"Plot.plot({\n x:{nice:true,grid:true,domain:[480,820]},\n y:{nice:true,grid:true,domain:[-0.1,1]},\n width:1000,\n marginTop:40,\n style: {fontSize: \"17px\"},\n marks: [\n Plot.ruleY([0]),\n Plot.dot(wuhan.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}), {x:'pos', y:'change' ,stroke:'black',strokeWidth:0.4,fill:lineage_form.color_on,r:4}),\n //FCS\n Plot.ruleX([681,682,683,684],{strokeWidth:3,stroke:'orange',opacity:0.7}),\n \n //S2'\n Plot.ruleX([815],{strokeWidth:3,stroke:'orange',opacity:1}),\n Plot.tip(wuhan.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}), Plot.pointer({\n x: 'pos',\n y: 'change',\n title: (d) => [\"Amino Acid in Wuhan: \"+d.reference,\n \"Position: \"+d.pos,\n \"Change: \"+d.change,\n ].join(\"\\n\\n\")\n })),\n ],\n color: {\n scheme: lineage_form.color,\n legend:true,\n domain:[-0.2,0.2]\n },\n})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":283,"value":"## BA.2.86 Affected sites\nEach point is a site affected by the H655Y reversion in the BA2.86 spike. The orange bars show the position of the Furin Clevage Site and the S2' cleavage site.","pinned":false,"hidden":false,"mode":"md","author":"$undefined","summary":"$undefined","output":"","database":"$undefined"},{"id":8,"value":"Plot.plot({\n x:{nice:true,grid:true,domain:[480,820]},\n y:{nice:true,grid:true,domain:[-0.1,1]},\n width:1000,\n marginTop:40,\n style: {fontSize: \"17px\"},\n marks: [\n Plot.ruleY([0]),\n Plot.dot(ba286.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}), {x: 'pos', y:'change',stroke:'black',strokeWidth:0.4,fill:lineage_form.color_on,r:4}),\n //FCS\n Plot.ruleX([681,682,683,684],{strokeWidth:3,stroke:'orange',opacity:0.7}),\n \n //S2'\n Plot.ruleX([815],{strokeWidth:3,stroke:'orange',opacity:1}),\n Plot.tip(ba286.filter(d=>{if(d.change>0.01 || d.change<-0.01){return d}else{return}}), Plot.pointer({\n x: 'pos',\n y: 'change',\n title: (d) => [\"Amino Acid in BA2.86: \"+d.reference,\n \"Position: \"+d.pos,\n \"Change: \"+d.change,\n ].join(\"\\n\\n\")\n })),\n \n ],\n color: {\n scheme: lineage_form.color,\n legend:true,\n domain:[-0.2,0.2]\n },\n})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":10,"value":"ba286 = FileAttachment(\"BA286_H655Y@1.csv\").csv({typed:true})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"},{"id":22,"value":"wuhan = FileAttachment(\"Wuhan_H655Y_Spike_Epistasis_Softmax@1.csv\").csv({typed:true})","pinned":false,"hidden":false,"mode":"ojs","author":"$undefined","summary":"$undefined","output":"$undefined","database":"$undefined"}],"files":"$W32","stdlib":"1","titling":"auto"}} 30:"$2f:body"