@sjcrh/proteinpaint-client 2.198.0 → 2.200.0

package/dist/bubbleHeatmap-IL44M4QZ.js.map

@@ -0,0 +1,7 @@
+{
+  "version": 3,
+  "sources": ["../plots/bubbleHeatmap.ts"],
+  "sourcesContent": ["import type { MassState, BasePlotConfig } from '#mass/types/mass'\nimport { getCompInit, copyMerge, type RxComponent } from '#rx'\nimport { PlotBase } from './PlotBase'\nimport { Menu, addGeneSearchbox, LegendCircleReference } from '#dom'\nimport { dofetch3 } from '#common/dofetch'\nimport { scaleLinear, scaleSqrt } from 'd3'\n\nconst defaultConfig = { chartType: 'bubbleHeatmap' }\n\nconst CELL_W = 92\nconst CELL_H = 64 // minimum row height\nconst ROW_LABEL_W = 170\nconst COL_LABEL_H = 92\nconst SITE_DOT_R = 5 // per-site dot radius (PTM)\nconst SITE_DOT_SP = 13 // center-to-center spacing when packing site dots\nconst CELL_PAD = 8\nconst MIN_DOT_R = 8 // protein-level (non-PTM) big dot, min radius\nconst MAX_DOT_R = 20 // protein-level (non-PTM) big dot, max radius\n// cap on \u2212log10(FDR) used for dot size, so one ultra-significant (or FDR=0) dot can't\n// dwarf the rest; FDR \u2264 10^\u2212CAP all render at the max size\nconst NEG_LOG_FDR_CAP = 10\n\nclass BubbleHeatmap extends PlotBase implements RxComponent {\n\tstatic type = 'bubbleHeatmap'\n\ttype: string\n\tdom!: { holder: any; body: any; tip: Menu; header?: any }\n\tcomponents: any\n\tdata: any\n\tcurrentIsoform = ''\n\tuseAdjusted = false\n\tgridHolder: any\n\n\tconstructor(opts: any, api) {\n\t\tsuper(opts, api)\n\t\tthis.type = BubbleHeatmap.type\n\t\tthis.components = {}\n\t}\n\n\tasync init() {\n\t\tconst holder = this.opts.holder.append('div').style('padding', '10px')\n\t\tthis.dom = {\n\t\t\tholder,\n\t\t\tbody: holder.append('div'),\n\t\t\ttip: new Menu({ padding: '' }),\n\t\t\theader: this.opts.header\n\t\t}\n\t\tif (this.dom.header) this.dom.header.html('Bubble Heatmap')\n\t}\n\n\tgetState(appState: MassState) {\n\t\tconst config: any = appState.plots.find((p: BasePlotConfig) => p.id === this.id)\n\t\tif (!config) throw `No plot with id='${this.id}' found`\n\t\treturn { config }\n\t}\n\n\tasync main() {\n\t\tconst gene = this.state.config?.gene\n\t\tif (!gene) throw new Error('bubbleHeatmap: gene is missing')\n\n\t\tif (this.dom.header) this.dom.header.text(`Bubble Heatmap: ${gene}`)\n\n\t\tconst body = {\n\t\t\tgenome: this.app.opts.state.vocab.genome,\n\t\t\tdslabel: this.app.opts.state.vocab.dslabel,\n\t\t\tgene\n\t\t}\n\n\t\tconst data = await dofetch3('termdb/bubbleHeatmap', { body })\n\t\tif (data.error) throw data.error\n\t\tthis.data = data\n\n\t\tthis.dom.body.selectAll('*').remove()\n\n\t\tconst isoformIds = Object.keys(data.isoforms)\n\t\tif (isoformIds.length === 0) {\n\t\t\tthis.dom.body\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '20px')\n\t\t\t\t.style('color', '#666')\n\t\t\t\t.text(`No data found for gene \"${gene}\" in any (assay, cohort) DAPfile.`)\n\t\t\treturn\n\t\t}\n\n\t\t// default to protein-abundance-adjusted values when a reference assay exists\n\t\tthis.useAdjusted = !!data.proteinReferenceAssay\n\t\tthis.currentIsoform = isoformIds[0]\n\n\t\t// isoform selector (the adjusted/raw toggle lives in the legend, by renderLegend)\n\t\tconst isoBlock = this.dom.body.append('div').style('margin-bottom', '12px')\n\t\tisoBlock.append('span').style('font-weight', 'bold').text('Isoform: ')\n\t\tif (isoformIds.length > 1) {\n\t\t\tconst sel = isoBlock\n\t\t\t\t.append('select')\n\t\t\t\t.style('margin-left', '5px')\n\t\t\t\t.style('padding', '3px 6px')\n\t\t\t\t.on('change', () => {\n\t\t\t\t\tthis.currentIsoform = sel.node().value\n\t\t\t\t\tthis.renderGrid()\n\t\t\t\t})\n\t\t\tsel\n\t\t\t\t.selectAll('option')\n\t\t\t\t.data(isoformIds)\n\t\t\t\t.enter()\n\t\t\t\t.append('option')\n\t\t\t\t.attr('value', (d: string) => d)\n\t\t\t\t.text((d: string) => `${data.isoforms[d].gene_name} \u2014 ${d}`)\n\t\t} else {\n\t\t\tisoBlock\n\t\t\t\t.append('span')\n\t\t\t\t.style('margin-left', '5px')\n\t\t\t\t.text(`${data.isoforms[this.currentIsoform].gene_name} \u2014 ${this.currentIsoform}`)\n\t\t}\n\n\t\tthis.gridHolder = this.dom.body.append('div')\n\t\tthis.renderGrid()\n\t}\n\n\trenderGrid() {\n\t\tconst data = this.data\n\t\tconst selectedIsoform = this.currentIsoform\n\t\tconst useAdjusted = this.useAdjusted\n\t\tconst refAssay: string | null = data.proteinReferenceAssay\n\t\tconst threshold: number = data.fdrThreshold\n\n\t\tthis.gridHolder.selectAll('*').remove()\n\t\tconst container = this.gridHolder\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '24px')\n\t\t\t.style('align-items', 'flex-start')\n\t\t\t.style('flex-wrap', 'wrap')\n\n\t\tconst isoformData = data.isoforms[selectedIsoform]\n\t\tif (!isoformData) return\n\n\t\tconst assays: string[] = data.assays\n\t\tconst cohorts: string[] = data.cohorts\n\t\tconst nRows = assays.length\n\t\tconst nCols = cohorts.length\n\n\t\tconst ptmAssays = new Set<string>(data.ptmAssays || [])\n\t\tconst isPTMassay = (assay: string) => ptmAssays.has(assay)\n\n\t\t// value the dot's color encodes: adjusted when requested & available, else raw\n\t\tconst valueOf = (s: any): number => this.valueFor(s, useAdjusted)\n\t\t// significance as \u2212log10(FDR), capped (guards FDR<=0 and keeps the size range sane).\n\t\tconst negLogFdr = (fdr: number): number => (fdr > 0 ? Math.min(-Math.log10(fdr), NEG_LOG_FDR_CAP) : NEG_LOG_FDR_CAP)\n\n\t\t// PTM assays show one small dot per site; build an ordered list of distinct site\n\t\t// ids (stable across cohort columns) so a site keeps the same slot in every column.\n\t\t// A site earns a slot if it is significant in at least one cohort; within a cohort\n\t\t// only the sites significant THERE are drawn, so a slot can render in one column and\n\t\t// stay empty in another. Sites never significant in any cohort are not rendered.\n\t\t// non-PTM assays show a single big dot.\n\t\tconst slotIndex = new Map<string, number>() // `${assay}|${id}` \u2192 slot\n\t\tconst assaySlotCount = new Map<string, number>()\n\t\tlet maxAbs = 0\n\t\t// \u2212log10(FDR) at the significance cutoff (~1.30 for FDR<0.05): the smallest sized\n\t\t// protein dot. maxNegLog grows to the most-significant protein dot shown.\n\t\tconst thresholdNegLog = negLogFdr(threshold)\n\t\tlet maxNegLog = thresholdNegLog\n\t\tfor (const assay of assays) {\n\t\t\tconst ptm = isPTMassay(assay)\n\t\t\t// per-site maps (PTM only) feed the stable slot order; raw log2FC so the order\n\t\t\t// doesn't shift with the adjusted/raw toggle\n\t\t\tconst rawSum = new Map<string, number>()\n\t\t\tconst rawN = new Map<string, number>()\n\t\t\tconst significantSomewhere = new Set<string>()\n\t\t\tfor (const cohort of cohorts) {\n\t\t\t\tconst cell = isoformData.data[assay]?.[cohort]\n\t\t\t\tif (!cell) continue\n\t\t\t\tif (ptm) {\n\t\t\t\t\t// PTM draws one dot per site significant in this cohort; the color\n\t\t\t\t\t// domain reflects only those drawn sites.\n\t\t\t\t\tfor (const s of cell.sites) {\n\t\t\t\t\t\tif (s.significant) {\n\t\t\t\t\t\t\tconst v = Math.abs(valueOf(s))\n\t\t\t\t\t\t\tif (v > maxAbs) maxAbs = v\n\t\t\t\t\t\t}\n\t\t\t\t\t\trawSum.set(s.id, (rawSum.get(s.id) ?? 0) + s.log2FC)\n\t\t\t\t\t\trawN.set(s.id, (rawN.get(s.id) ?? 0) + 1)\n\t\t\t\t\t\tif (s.significant) significantSomewhere.add(s.id)\n\t\t\t\t\t}\n\t\t\t\t} else {\n\t\t\t\t\t// non-PTM draws only the single best row (cell.sites[0]); size = -log10(FDR)\n\t\t\t\t\tconst s = cell.sites[0]\n\t\t\t\t\tif (!s) continue\n\t\t\t\t\tconst v = Math.abs(valueOf(s))\n\t\t\t\t\tif (v > maxAbs) maxAbs = v\n\t\t\t\t\tconst nl = negLogFdr(s.fdr)\n\t\t\t\t\tif (nl > maxNegLog) maxNegLog = nl\n\t\t\t\t}\n\t\t\t}\n\t\t\tif (ptm) {\n\t\t\t\t// direction then magnitude: most up-regulated first \u2192 most down-regulated,\n\t\t\t\t// ranked by mean raw log2FC (descending) so up/down sites group as a gradient.\n\t\t\t\t// only sites significant in some cohort earn a slot.\n\t\t\t\tconst meanRaw = (id: string) => rawSum.get(id)! / rawN.get(id)!\n\t\t\t\tconst ordered = [...significantSomewhere].sort((a, b) => meanRaw(b) - meanRaw(a))\n\t\t\t\tordered.forEach((id, i) => slotIndex.set(`${assay}|${id}`, i))\n\t\t\t\tassaySlotCount.set(assay, ordered.length)\n\t\t\t} else {\n\t\t\t\tassaySlotCount.set(assay, 1) // single big dot per cell\n\t\t\t}\n\t\t}\n\t\tif (maxAbs === 0) maxAbs = 1\n\t\t// guarantee a non-degenerate size domain when no protein dot is more significant\n\t\t// than the cutoff (e.g. only the best, still non-significant, row is shown)\n\t\tif (maxNegLog <= thresholdNegLog) maxNegLog = thresholdNegLog + 1\n\n\t\tconst colorScale = scaleLinear<string>()\n\t\t\t.domain([-maxAbs, 0, maxAbs])\n\t\t\t.range(['#2166ac', '#f7f7f7', '#b2182b'])\n\t\t\t.clamp(true)\n\t\t// non-PTM big-dot size encodes significance as \u2212log10(FDR): bigger = more\n\t\t// significant. domain runs from the FDR<threshold cutoff to the most-significant\n\t\t// protein dot; non-significant dots clamp to the smallest size. color carries\n\t\t// log2FC, so size and color encode two independent variables.\n\t\tconst sizeScale = scaleSqrt().domain([thresholdNegLog, maxNegLog]).range([MIN_DOT_R, MAX_DOT_R]).clamp(true)\n\n\t\t// per-row layout: sub-columns and row height grow with the site count\n\t\tconst layout = assays.map(assay => {\n\t\t\tconst m = assaySlotCount.get(assay)!\n\t\t\tconst subCols = Math.max(1, Math.min(m, Math.floor((CELL_W - 2 * CELL_PAD) / SITE_DOT_SP)))\n\t\t\tconst rows = Math.ceil(m / subCols)\n\t\t\treturn { subCols, rows, height: Math.max(CELL_H, rows * SITE_DOT_SP + 2 * CELL_PAD) }\n\t\t})\n\t\tconst rowY: number[] = []\n\t\tlet yAcc = COL_LABEL_H\n\t\tfor (let r = 0; r < nRows; r++) {\n\t\t\trowY[r] = yAcc\n\t\t\tyAcc += layout[r].height\n\t\t}\n\t\tconst gridW = ROW_LABEL_W + nCols * CELL_W + 20\n\t\tconst gridH = yAcc + 20\n\n\t\tconst svg = container.append('svg').attr('width', gridW).attr('height', gridH).style('flex', '0 0 auto')\n\t\tconst grid = svg.append('g')\n\n\t\t// column labels (cohorts), rotated\n\t\tfor (let c = 0; c < nCols; c++) {\n\t\t\tconst cx = ROW_LABEL_W + c * CELL_W + CELL_W / 2\n\t\t\tgrid\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', cx)\n\t\t\t\t.attr('y', COL_LABEL_H - 10)\n\t\t\t\t.attr('text-anchor', 'start')\n\t\t\t\t.attr('font-size', '12px')\n\t\t\t\t.attr('font-weight', 'bold')\n\t\t\t\t.attr('transform', `rotate(-35 ${cx} ${COL_LABEL_H - 10})`)\n\t\t\t\t.text(cohorts[c])\n\t\t}\n\n\t\t// row labels (assays) with site counts\n\t\tfor (let r = 0; r < nRows; r++) {\n\t\t\tconst cy = rowY[r] + layout[r].height / 2\n\t\t\tconst m = assaySlotCount.get(assays[r])!\n\t\t\tconst lbl = grid\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', ROW_LABEL_W - 10)\n\t\t\t\t.attr('y', cy)\n\t\t\t\t.attr('text-anchor', 'end')\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.attr('font-size', '12px')\n\t\t\t\t.attr('font-weight', 'bold')\n\t\t\tlbl.append('tspan').text(assays[r])\n\t\t\tlbl\n\t\t\t\t.append('tspan')\n\t\t\t\t.attr('x', ROW_LABEL_W - 10)\n\t\t\t\t.attr('dy', '1.3em')\n\t\t\t\t.attr('font-weight', 'normal')\n\t\t\t\t.attr('font-size', '10px')\n\t\t\t\t.attr('fill', '#888')\n\t\t\t\t.text(m > 1 ? `${m} sites` : '')\n\t\t}\n\n\t\t// cells: guideline + dots (small per-site for PTM, one big dot for non-PTM)\n\t\tfor (let r = 0; r < nRows; r++) {\n\t\t\tconst assay = assays[r]\n\t\t\tconst ptm = isPTMassay(assay)\n\t\t\tconst { subCols, height } = layout[r]\n\n\t\t\tfor (let c = 0; c < nCols; c++) {\n\t\t\t\tconst x0 = ROW_LABEL_W + c * CELL_W\n\t\t\t\tconst y0 = rowY[r]\n\n\t\t\t\tgrid\n\t\t\t\t\t.append('rect')\n\t\t\t\t\t.attr('x', x0)\n\t\t\t\t\t.attr('y', y0)\n\t\t\t\t\t.attr('width', CELL_W)\n\t\t\t\t\t.attr('height', height)\n\t\t\t\t\t.attr('fill', 'none')\n\t\t\t\t\t.attr('stroke', '#eee')\n\t\t\t\t\t.attr('stroke-width', 1)\n\n\t\t\t\tconst cell = isoformData.data[assay]?.[cohorts[c]]\n\t\t\t\tif (!cell || !cell.sites.length) continue\n\n\t\t\t\tconst addDot = (s: any, cx: number, cy: number, radius: number) => {\n\t\t\t\t\t// color = log2FC; protein-level size = significance. non-significant dots are\n\t\t\t\t\t// also faded via element opacity (fades fill + outline together, so a\n\t\t\t\t\t// small dot reads as \"weak\"). the constant thin outline keeps near-white\n\t\t\t\t\t// (~0 log2FC) dots legible, not a significance cue.\n\t\t\t\t\treturn grid\n\t\t\t\t\t\t.append('circle')\n\t\t\t\t\t\t.attr('cx', cx)\n\t\t\t\t\t\t.attr('cy', cy)\n\t\t\t\t\t\t.attr('r', radius)\n\t\t\t\t\t\t.attr('fill', colorScale(valueOf(s)))\n\t\t\t\t\t\t.attr('stroke', '#888')\n\t\t\t\t\t\t.attr('stroke-width', 0.8)\n\t\t\t\t\t\t.style('opacity', s.significant ? 1 : 0.35)\n\t\t\t\t\t\t.on('mouseover', (event: MouseEvent) =>\n\t\t\t\t\t\t\tthis.showSiteTip(\n\t\t\t\t\t\t\t\tevent,\n\t\t\t\t\t\t\t\tisoformData.gene_name,\n\t\t\t\t\t\t\t\tselectedIsoform,\n\t\t\t\t\t\t\t\tassay,\n\t\t\t\t\t\t\t\tcohorts[c],\n\t\t\t\t\t\t\t\ts,\n\t\t\t\t\t\t\t\tuseAdjusted,\n\t\t\t\t\t\t\t\trefAssay\n\t\t\t\t\t\t\t)\n\t\t\t\t\t\t)\n\t\t\t\t\t\t.on('mouseout', () => this.dom.tip.hide())\n\t\t\t\t}\n\n\t\t\t\tif (!ptm) {\n\t\t\t\t\t// single big dot (protein level): color = log2FC, size = \u2212log10(FDR) so\n\t\t\t\t\t// the dot shows effect and significance as two independent channels.\n\t\t\t\t\tconst s = cell.sites[0]\n\t\t\t\t\tconst cx = x0 + CELL_W / 2\n\t\t\t\t\tconst cy = y0 + height / 2\n\t\t\t\t\taddDot(s, cx, cy, sizeScale(negLogFdr(s.fdr)))\n\t\t\t\t\tcontinue\n\t\t\t\t}\n\n\t\t\t\t// PTM: small fixed-radius dot per site, packed at stable slots.\n\t\t\t\t// only sites significant in THIS cohort render; a site keeps its slot\n\t\t\t\t// (reserved from being significant in some cohort) so positions stay stable.\n\t\t\t\tconst blockW = subCols * SITE_DOT_SP\n\t\t\t\tconst blockH = layout[r].rows * SITE_DOT_SP\n\t\t\t\tconst startX = x0 + (CELL_W - blockW) / 2 + SITE_DOT_SP / 2\n\t\t\t\tconst startY = y0 + (height - blockH) / 2 + SITE_DOT_SP / 2\n\t\t\t\tfor (const s of cell.sites) {\n\t\t\t\t\tif (!s.significant) continue // hide PTM sites not significant in this cohort\n\t\t\t\t\t// significant \u27F9 significant-somewhere \u27F9 always has a slot\n\t\t\t\t\tconst slot = slotIndex.get(`${assay}|${s.id}`)!\n\t\t\t\t\tconst cx = startX + (slot % subCols) * SITE_DOT_SP\n\t\t\t\t\tconst cy = startY + Math.floor(slot / subCols) * SITE_DOT_SP\n\t\t\t\t\taddDot(s, cx, cy, SITE_DOT_R)\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\tthis.renderLegend(container, colorScale, maxAbs, threshold, useAdjusted, refAssay, maxNegLog)\n\t}\n\n\tprivate fmtFdr(v: number): string {\n\t\treturn v >= 0.0001 ? v.toFixed(4) : v.toExponential(2)\n\t}\n\n\t/** true when the protein-adjusted value should be shown instead of raw log2FC */\n\tprivate showsAdjusted(s: any, useAdjusted: boolean): boolean {\n\t\treturn !!(useAdjusted && s.adjustedAvailable && s.adjustedLog2FC != null)\n\t}\n\n\t/** value encoded by color: protein-adjusted when requested & available, else raw */\n\tprivate valueFor(s: any, useAdjusted: boolean): number {\n\t\treturn this.showsAdjusted(s, useAdjusted) ? s.adjustedLog2FC : s.log2FC\n\t}\n\n\tprivate showSiteTip(\n\t\tevent: MouseEvent,\n\t\tgeneName: string,\n\t\tisoform: string,\n\t\tassay: string,\n\t\tcohort: string,\n\t\ts: any,\n\t\tuseAdjusted: boolean,\n\t\trefAssay: string | null\n\t) {\n\t\tthis.dom.tip.clear().show(event.clientX, event.clientY)\n\t\tconst t = this.dom.tip.d.append('div').style('padding', '8px').style('font-size', '13px')\n\t\tt.append('div').style('font-weight', 'bold').style('margin-bottom', '4px').text(`${geneName} \u2014 ${isoform}`)\n\t\tt.append('div').text(`Assay: ${assay}`)\n\t\tt.append('div').text(`Sample set: ${cohort}`)\n\t\tconst isPTM = (this.data.ptmAssays || []).includes(assay)\n\t\tt.append('div').text(`${isPTM ? 'Site' : 'Protein'}: ${s.id}`)\n\t\tt.append('div').text(`raw log\u2082FC: ${s.log2FC.toFixed(3)}`)\n\t\tif (s.adjustedAvailable) {\n\t\t\tt.append('div').text(`protein log\u2082FC: ${s.proteinLog2FC.toFixed(3)}`)\n\t\t\tt.append('div').text(`adjusted log\u2082FC: ${s.adjustedLog2FC.toFixed(3)}`)\n\t\t} else if (refAssay && isPTM) {\n\t\t\tt.append('div').style('color', '#999').text('adjusted: n/a (protein not measured)')\n\t\t}\n\t\tt.append('div').text(`FDR: ${this.fmtFdr(s.fdr)}`)\n\t\tconst shown = this.showsAdjusted(s, useAdjusted) ? 'adjusted' : 'raw'\n\t\tt.append('div').style('color', '#666').style('margin-top', '4px').text(`Color = ${shown} log\u2082FC.`)\n\t}\n\n\tprivate renderLegend(\n\t\tcontainer: any,\n\t\tcolorScale: any,\n\t\tmaxAbs: number,\n\t\tthreshold: number,\n\t\tuseAdjusted: boolean,\n\t\trefAssay: string | null,\n\t\tmaxNegLog: number\n\t) {\n\t\tconst legend = container\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('flex-direction', 'column')\n\t\t\t.style('gap', '16px')\n\t\t\t.style('padding', '8px 0')\n\t\t\t.style('min-width', '180px')\n\t\t\t.style('max-width', '260px')\n\n\t\t// color scale\n\t\tconst colorBlock = legend.append('div')\n\t\tcolorBlock\n\t\t\t.append('div')\n\t\t\t.style('font-weight', 'bold')\n\t\t\t.style('font-size', '13px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.text(useAdjusted && refAssay ? 'log\u2082FC (PTM-adjusted)' : 'log\u2082FC')\n\t\tconst cW = 22\n\t\tconst cH = 130\n\t\tconst cSvg = colorBlock\n\t\t\t.append('svg')\n\t\t\t.attr('width', cW + 60)\n\t\t\t.attr('height', cH + 16)\n\t\tconst gid = `bh-grad-${this.id}`\n\t\tconst grad = cSvg\n\t\t\t.append('defs')\n\t\t\t.append('linearGradient')\n\t\t\t.attr('id', gid)\n\t\t\t.attr('x1', '0')\n\t\t\t.attr('y1', '0')\n\t\t\t.attr('x2', '0')\n\t\t\t.attr('y2', '1')\n\t\tconst steps = 10\n\t\tfor (let i = 0; i <= steps; i++) {\n\t\t\tconst t = i / steps\n\t\t\tgrad\n\t\t\t\t.append('stop')\n\t\t\t\t.attr('offset', `${t * 100}%`)\n\t\t\t\t.attr('stop-color', colorScale(maxAbs * (1 - 2 * t)))\n\t\t}\n\t\tcSvg\n\t\t\t.append('rect')\n\t\t\t.attr('x', 0)\n\t\t\t.attr('y', 8)\n\t\t\t.attr('width', cW)\n\t\t\t.attr('height', cH)\n\t\t\t.style('fill', `url(#${gid})`)\n\t\t\t.attr('stroke', '#999')\n\t\tconst cScale = scaleLinear()\n\t\t\t.domain([maxAbs, -maxAbs])\n\t\t\t.range([8, cH + 8])\n\t\tfor (const tick of [maxAbs, maxAbs / 2, 0, -maxAbs / 2, -maxAbs]) {\n\t\t\tconst y = cScale(tick)\n\t\t\tcSvg\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', cW)\n\t\t\t\t.attr('y1', y)\n\t\t\t\t.attr('x2', cW + 5)\n\t\t\t\t.attr('y2', y)\n\t\t\t\t.attr('stroke', '#666')\n\t\t\tcSvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', cW + 8)\n\t\t\t\t.attr('y', y)\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.attr('font-size', '10px')\n\t\t\t\t.text(tick.toFixed(2))\n\t\t}\n\n\t\t// size key \u2014 protein-level (non-PTM) big dot, sized by significance (\u2212log10 FDR)\n\t\tconst sizeBlock = legend.append('div')\n\t\tsizeBlock\n\t\t\t.append('div')\n\t\t\t.style('font-weight', 'bold')\n\t\t\t.style('font-size', '13px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.text('Non-PTM dot size: significance (\u2212log\u2081\u2080 FDR)')\n\t\t// small circle = the FDR<threshold cutoff, large circle = the most-significant\n\t\t// protein shown.\n\t\tconst sSvg = sizeBlock.append('svg')\n\t\tconst sG = sSvg.append('g')\n\t\tnew LegendCircleReference({\n\t\t\tg: sG,\n\t\t\tinputMin: 0,\n\t\t\tinputMax: MAX_DOT_R * 2,\n\t\t\tminRadius: MIN_DOT_R,\n\t\t\tmaxRadius: MAX_DOT_R,\n\t\t\t// capped to match the size scale's domain min (thresholdNegLog in renderGrid)\n\t\t\tminLabel: Number(Math.min(-Math.log10(threshold), NEG_LOG_FDR_CAP).toFixed(1)),\n\t\t\tmaxLabel: Number(maxNegLog.toFixed(1))\n\t\t})\n\t\t// fit the SVG to the rendered legend (plus a small margin) so it doesn't reserve\n\t\t// excess space; shift the group so its content starts at the margin.\n\t\tconst sPad = 4\n\t\tconst sBox = sG.node().getBBox()\n\t\tsG.attr('transform', `translate(${sPad - sBox.x}, ${sPad - sBox.y})`)\n\t\tsSvg.attr('width', Math.ceil(sBox.width + 2 * sPad)).attr('height', Math.ceil(sBox.height + 2 * sPad))\n\n\t\t// values toggle \u2014 placed below the dot-size key, right above the note that\n\t\t// explains what \"adjusted\" means. The reference assay itself is never adjusted.\n\t\tif (refAssay) {\n\t\t\tconst adjLabel = legend\n\t\t\t\t.append('div')\n\t\t\t\t.append('label')\n\t\t\t\t.style('display', 'flex')\n\t\t\t\t.style('align-items', 'center')\n\t\t\t\t.style('gap', '6px')\n\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t.style('font-size', '13px')\n\t\t\t\t.style('font-weight', 'bold')\n\t\t\t\t.attr(\n\t\t\t\t\t'title',\n\t\t\t\t\t`When checked, the PTM assays have the ${refAssay} log\u2082FC subtracted; other assays are shown unchanged.`\n\t\t\t\t)\n\t\t\tconst adjCb = adjLabel\n\t\t\t\t.append('input')\n\t\t\t\t.attr('type', 'checkbox')\n\t\t\t\t.property('checked', this.useAdjusted)\n\t\t\t\t.on('change', () => {\n\t\t\t\t\tthis.useAdjusted = adjCb.property('checked')\n\t\t\t\t\tthis.renderGrid()\n\t\t\t\t})\n\t\t\tadjLabel.append('span').style('font-weight', 'normal').text('Adjust PTM for total protein abundance')\n\t\t}\n\n\t\tconst notes = legend\n\t\t\t.append('div')\n\t\t\t.style('font-size', '11px')\n\t\t\t.style('color', '#666')\n\t\t\t.style('line-height', '1.5')\n\t\t\t.style('max-width', '240px')\n\t\t\t.style('overflow-wrap', 'break-word')\n\t\tnotes\n\t\t\t.append('div')\n\t\t\t.text(\n\t\t\t\t`Color = log\u2082FC. Dot size = significance, \u2212log\u2081\u2080 FDR (non-PTM rows); the smallest size marks the FDR < ${threshold} cutoff. Non-significant dots are faded.`\n\t\t\t)\n\t\tnotes\n\t\t\t.append('div')\n\t\t\t.style('margin-top', '4px')\n\t\t\t.text(\n\t\t\t\t'PTM rows: one fixed-size dot per site significant in that cohort, positions stable across cohorts; non-significant sites are not shown.'\n\t\t\t)\n\t\tnotes\n\t\t\t.append('div')\n\t\t\t.style('margin-top', '4px')\n\t\t\t.text(\n\t\t\t\t'A slot stays empty where the site is not significant in that cohort, the assay was not performed, or the protein was not detected.'\n\t\t\t)\n\t\tif (refAssay) {\n\t\t\tnotes\n\t\t\t\t.append('div')\n\t\t\t\t.style('margin-top', '4px')\n\t\t\t\t.text(`Adjusted log\u2082FC = a PTM site's log\u2082FC \u2212 ${refAssay} log\u2082FC (PTM assays only).`)\n\t\t}\n\t}\n}\n\nexport const componentInit = getCompInit(BubbleHeatmap)\n\nexport async function getPlotConfig(opts: any) {\n\tconst config = structuredClone(defaultConfig)\n\tif (!opts.gene) throw new Error('bubbleHeatmap requires opts.gene')\n\treturn copyMerge(config, opts)\n}\n\nexport function makeChartBtnMenu(holder: any, chartsInstance: any) {\n\tconst row = holder.append('div').style('padding', '5px')\n\trow.append('span').style('font-weight', 'bold').text('Enter a gene name:')\n\n\tconst geneSearch = addGeneSearchbox({\n\t\trow,\n\t\tgenome: chartsInstance.app.opts.genome,\n\t\ttip: new Menu({ padding: '0px' }),\n\t\tsearchOnly: 'gene',\n\t\tcallback: async () => {\n\t\t\tif (!geneSearch.geneSymbol) throw new Error('A valid gene selection is required')\n\t\t\tchartsInstance.dom.tip.hide()\n\t\t\tchartsInstance.app.dispatch({\n\t\t\t\ttype: 'plot_create',\n\t\t\t\tconfig: {\n\t\t\t\t\tchartType: 'bubbleHeatmap',\n\t\t\t\t\tgene: geneSearch.geneSymbol\n\t\t\t\t}\n\t\t\t})\n\t\t}\n\t})\n}\n"],
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+  "names": []
+}

package/dist/cellTypeBubbleHeatmap-NQP7RCZO.js

@@ -0,0 +1,283 @@
+import {
+  LegendCircleReference,
+  PlotBase,
+  addGeneSearchbox
+} from "./chunk-TKW5TW4Z.js";
+import "./chunk-HJ6L54YS.js";
+import "./chunk-LSEFWW72.js";
+import "./chunk-3SHZTAGF.js";
+import {
+  Menu
+} from "./chunk-HYOEWQ5P.js";
+import "./chunk-6QCYT6G2.js";
+import "./chunk-FN5XPUPH.js";
+import "./chunk-IIT367QZ.js";
+import "./chunk-RZGEKL77.js";
+import "./chunk-OTTMHVYH.js";
+import "./chunk-GNS6CQMA.js";
+import {
+  dofetch3
+} from "./chunk-JVPWIVDT.js";
+import "./chunk-4WF3XDQP.js";
+import "./chunk-7JRDJNLR.js";
+import {
+  copyMerge,
+  getCompInit
+} from "./chunk-M3J4MINX.js";
+import "./chunk-PF4DSFDR.js";
+import "./chunk-MPSLUEI4.js";
+import "./chunk-6PNPHACF.js";
+import "./chunk-WPHUM5S5.js";
+import "./chunk-JNITUVXP.js";
+import "./chunk-2KXLYFAO.js";
+import "./chunk-LOZEKOES.js";
+import "./chunk-VQZ2Z5YU.js";
+import {
+  linear,
+  sqrt
+} from "./chunk-UJELJXJG.js";
+import "./chunk-BZTWTH4Y.js";
+import "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import "./chunk-I6Y4O3RR.js";
+import "./chunk-Q5RDQNIT.js";
+import "./chunk-DQC5FFGV.js";
+import "./chunk-HFNDKYVF.js";
+
+// plots/cellTypeBubbleHeatmap.ts
+var defaultConfig = { chartType: "cellTypeBubbleHeatmap" };
+var CELL_W = 84;
+var CELL_H = 60;
+var ROW_LABEL_W = 74;
+var GROUP_LABEL_H = 22;
+var GENO_LABEL_H = 40;
+var COL_LABEL_H = GROUP_LABEL_H + GENO_LABEL_H;
+var MIN_DOT_R = 8;
+var MAX_DOT_R = 22;
+var NEG_LOG_FDR_CAP = 10;
+var COLOR_NEG = "#762a83";
+var COLOR_ZERO = "#f7f7f7";
+var COLOR_POS = "#2166ac";
+var CellTypeBubbleHeatmap = class _CellTypeBubbleHeatmap extends PlotBase {
+  constructor(opts, api) {
+    super(opts, api);
+    this.currentIsoform = "";
+    this.type = _CellTypeBubbleHeatmap.type;
+  }
+  static {
+    this.type = "cellTypeBubbleHeatmap";
+  }
+  async init() {
+    const holder = this.opts.holder.append("div").style("padding", "10px");
+    this.dom = {
+      holder,
+      body: holder.append("div"),
+      tip: new Menu({ padding: "" }),
+      header: this.opts.header
+    };
+    if (this.dom.header) this.dom.header.html("Cell-type Bubble Heatmap");
+  }
+  getState(appState) {
+    const config = appState.plots.find((p) => p.id === this.id);
+    if (!config) throw `No plot with id='${this.id}' found`;
+    return { config };
+  }
+  async main() {
+    const gene = this.state.config?.gene;
+    if (!gene) throw new Error("cellTypeBubbleHeatmap: gene is missing");
+    if (this.dom.header) this.dom.header.text(`Cell-type Bubble Heatmap: ${gene}`);
+    const body = {
+      genome: this.app.opts.state.vocab.genome,
+      dslabel: this.app.opts.state.vocab.dslabel,
+      gene
+    };
+    const data = await dofetch3("termdb/cellTypeBubbleHeatmap", { body });
+    if (data.error) throw data.error;
+    this.data = data;
+    this.dom.body.selectAll("*").remove();
+    const isoformIds = Object.keys(data.isoforms);
+    if (isoformIds.length === 0) {
+      this.dom.body.append("div").style("padding", "20px").style("color", "#666").text(`No data found for gene "${gene}" in any cohort DAPfile.`);
+      return;
+    }
+    this.currentIsoform = isoformIds[0];
+    const isoBlock = this.dom.body.append("div").style("margin-bottom", "12px");
+    isoBlock.append("span").style("font-weight", "bold").text("Isoform: ");
+    if (isoformIds.length > 1) {
+      const sel = isoBlock.append("select").style("margin-left", "5px").style("padding", "3px 6px").on("change", () => {
+        this.currentIsoform = sel.node().value;
+        this.renderGrid();
+      });
+      sel.selectAll("option").data(isoformIds).enter().append("option").attr("value", (d) => d).text((d) => `${data.isoforms[d].gene_name} \u2014 ${d}`);
+    } else {
+      isoBlock.append("span").style("margin-left", "5px").text(`${data.isoforms[this.currentIsoform].gene_name} \u2014 ${this.currentIsoform}`);
+    }
+    this.gridHolder = this.dom.body.append("div");
+    this.renderGrid();
+  }
+  renderGrid() {
+    const data = this.data;
+    const selectedIsoform = this.currentIsoform;
+    const threshold = data.fdrThreshold;
+    this.gridHolder.selectAll("*").remove();
+    const container = this.gridHolder.append("div").style("display", "flex").style("gap", "24px").style("align-items", "flex-start").style("flex-wrap", "wrap");
+    const isoformData = data.isoforms[selectedIsoform];
+    if (!isoformData) return;
+    const columns = data.columns;
+    const rows = data.rows;
+    const nCols = columns.length;
+    const nRows = rows.length;
+    const negLogFdr = (fdr) => fdr > 0 ? Math.min(-Math.log10(fdr), NEG_LOG_FDR_CAP) : NEG_LOG_FDR_CAP;
+    const cellOf = (colKey, rowKey) => isoformData.data[colKey]?.[rowKey];
+    let maxAbs = 0;
+    const thresholdNegLog = negLogFdr(threshold);
+    let maxNegLog = thresholdNegLog;
+    for (const col of columns) {
+      for (const row of rows) {
+        const s = cellOf(col.key, row.key);
+        if (!s) continue;
+        const v = Math.abs(s.log2FC);
+        if (v > maxAbs) maxAbs = v;
+        const nl = negLogFdr(s.fdr);
+        if (nl > maxNegLog) maxNegLog = nl;
+      }
+    }
+    if (maxAbs === 0) maxAbs = 1;
+    if (maxNegLog <= thresholdNegLog) maxNegLog = thresholdNegLog + 1;
+    const colorScale = linear().domain([-maxAbs, 0, maxAbs]).range([COLOR_NEG, COLOR_ZERO, COLOR_POS]).clamp(true);
+    const sizeScale = sqrt().domain([thresholdNegLog, maxNegLog]).range([MIN_DOT_R, MAX_DOT_R]).clamp(true);
+    const gridW = ROW_LABEL_W + nCols * CELL_W + 20;
+    const gridH = COL_LABEL_H + nRows * CELL_H + 20;
+    const svg = container.append("svg").attr("width", gridW).attr("height", gridH).style("flex", "0 0 auto");
+    const grid = svg.append("g");
+    let c = 0;
+    while (c < nCols) {
+      const cellType = columns[c].cellType;
+      let end = c;
+      while (end + 1 < nCols && columns[end + 1].cellType === cellType) end++;
+      const xStart = ROW_LABEL_W + c * CELL_W;
+      const xEnd = ROW_LABEL_W + (end + 1) * CELL_W;
+      const xMid = (xStart + xEnd) / 2;
+      grid.append("text").attr("x", xMid).attr("y", GROUP_LABEL_H - 7).attr("text-anchor", "middle").attr("font-size", "13px").attr("font-weight", "bold").text(cellType);
+      grid.append("line").attr("x1", xStart + 4).attr("y1", GROUP_LABEL_H - 3).attr("x2", xEnd - 4).attr("y2", GROUP_LABEL_H - 3).attr("stroke", "#bbb").attr("stroke-width", 1);
+      c = end + 1;
+    }
+    for (let col = 0; col < nCols; col++) {
+      const cx = ROW_LABEL_W + col * CELL_W + CELL_W / 2;
+      grid.append("text").attr("x", cx).attr("y", COL_LABEL_H - 14).attr("text-anchor", "middle").attr("font-size", "12px").attr("font-weight", "600").text(columns[col].genotype);
+    }
+    for (let r = 0; r < nRows; r++) {
+      const cy = COL_LABEL_H + r * CELL_H + CELL_H / 2;
+      grid.append("text").attr("x", ROW_LABEL_W - 12).attr("y", cy).attr("text-anchor", "end").attr("dominant-baseline", "central").attr("font-size", "13px").attr("font-weight", "bold").text(rows[r].label);
+    }
+    for (let r = 0; r < nRows; r++) {
+      for (let col = 0; col < nCols; col++) {
+        const x0 = ROW_LABEL_W + col * CELL_W;
+        const y0 = COL_LABEL_H + r * CELL_H;
+        grid.append("rect").attr("x", x0).attr("y", y0).attr("width", CELL_W).attr("height", CELL_H).attr("fill", "none").attr("stroke", "#eee").attr("stroke-width", 1);
+        const s = cellOf(columns[col].key, rows[r].key);
+        if (!s) continue;
+        const cx = x0 + CELL_W / 2;
+        const cy = y0 + CELL_H / 2;
+        grid.append("circle").attr("cx", cx).attr("cy", cy).attr("r", sizeScale(negLogFdr(s.fdr))).attr("fill", colorScale(s.log2FC)).attr("stroke", "#888").attr("stroke-width", 0.8).style("opacity", s.significant ? 1 : 0.35).on(
+          "mouseover",
+          (event) => this.showCellTip(event, isoformData.gene_name, selectedIsoform, columns[col], rows[r], s)
+        ).on("mouseout", () => this.dom.tip.hide());
+      }
+    }
+    this.renderLegend(container, colorScale, maxAbs, threshold, maxNegLog);
+  }
+  fmtFdr(v) {
+    return v >= 1e-4 ? v.toFixed(4) : v.toExponential(2);
+  }
+  showCellTip(event, geneName, isoform, col, row, s) {
+    this.dom.tip.clear().show(event.clientX, event.clientY);
+    const t = this.dom.tip.d.append("div").style("padding", "8px").style("font-size", "13px");
+    t.append("div").style("font-weight", "bold").style("margin-bottom", "4px").text(`${geneName} \u2014 ${isoform}`);
+    t.append("div").text(`Cell type: ${col.cellType}`);
+    t.append("div").text(`Genotype: ${col.genotype}`);
+    t.append("div").text(`Timepoint: ${row.label}`);
+    t.append("div").text(`Protein: ${s.id}`);
+    t.append("div").text(`log\u2082FC: ${s.log2FC.toFixed(3)}`);
+    t.append("div").text(`FDR: ${this.fmtFdr(s.fdr)}${s.significant ? "" : " (n.s.)"}`);
+    t.append("div").style("color", "#666").style("margin-top", "4px").text("Color = log\u2082FC (blue up / purple down). Size = \u2212log\u2081\u2080 FDR.");
+  }
+  renderLegend(container, colorScale, maxAbs, threshold, maxNegLog) {
+    const legend = container.append("div").style("display", "flex").style("flex-direction", "column").style("gap", "16px").style("padding", "8px 0").style("min-width", "180px").style("max-width", "260px");
+    const colorBlock = legend.append("div");
+    colorBlock.append("div").style("font-weight", "bold").style("font-size", "13px").style("margin-bottom", "6px").text("log\u2082FC");
+    const cW = 22;
+    const cH = 130;
+    const cSvg = colorBlock.append("svg").attr("width", cW + 80).attr("height", cH + 16);
+    const gid = `ctbh-grad-${this.id}`;
+    const grad = cSvg.append("defs").append("linearGradient").attr("id", gid).attr("x1", "0").attr("y1", "0").attr("x2", "0").attr("y2", "1");
+    const steps = 10;
+    for (let i = 0; i <= steps; i++) {
+      const t = i / steps;
+      grad.append("stop").attr("offset", `${t * 100}%`).attr("stop-color", colorScale(maxAbs * (1 - 2 * t)));
+    }
+    cSvg.append("rect").attr("x", 0).attr("y", 8).attr("width", cW).attr("height", cH).style("fill", `url(#${gid})`).attr("stroke", "#999");
+    const cScale = linear().domain([maxAbs, -maxAbs]).range([8, cH + 8]);
+    for (const tick of [maxAbs, maxAbs / 2, 0, -maxAbs / 2, -maxAbs]) {
+      const y = cScale(tick);
+      cSvg.append("line").attr("x1", cW).attr("y1", y).attr("x2", cW + 5).attr("y2", y).attr("stroke", "#666");
+      cSvg.append("text").attr("x", cW + 8).attr("y", y).attr("dominant-baseline", "central").attr("font-size", "10px").text(`${tick > 0 ? "+" : ""}${tick.toFixed(2)}`);
+    }
+    colorBlock.append("div").style("font-size", "11px").style("color", "#666").style("margin-top", "2px").text("blue = up (+), purple = down (\u2212)");
+    const sizeBlock = legend.append("div");
+    sizeBlock.append("div").style("font-weight", "bold").style("font-size", "13px").style("margin-bottom", "6px").text("Dot size: significance (\u2212log\u2081\u2080 FDR)");
+    const sSvg = sizeBlock.append("svg");
+    const sG = sSvg.append("g");
+    new LegendCircleReference({
+      g: sG,
+      inputMin: 0,
+      inputMax: MAX_DOT_R * 2,
+      minRadius: MIN_DOT_R,
+      maxRadius: MAX_DOT_R,
+      minLabel: Number(Math.min(-Math.log10(threshold), NEG_LOG_FDR_CAP).toFixed(1)),
+      maxLabel: Number(maxNegLog.toFixed(1))
+    });
+    const sPad = 4;
+    const sBox = sG.node().getBBox();
+    sG.attr("transform", `translate(${sPad - sBox.x}, ${sPad - sBox.y})`);
+    sSvg.attr("width", Math.ceil(sBox.width + 2 * sPad)).attr("height", Math.ceil(sBox.height + 2 * sPad));
+    const notes = legend.append("div").style("font-size", "11px").style("color", "#666").style("line-height", "1.5").style("max-width", "240px").style("overflow-wrap", "break-word");
+    notes.append("div").text(
+      `Color = log\u2082FC (blue up, purple down). Dot size = significance, \u2212log\u2081\u2080 FDR; the smallest size marks the FDR < ${threshold} cutoff. Non-significant dots (FDR \u2265 ${threshold}) are faded.`
+    );
+    notes.append("div").style("margin-top", "4px").text("An empty cell means the cohort was not assayed (e.g. OPC has no 4m) or the protein was not detected.");
+  }
+};
+var componentInit = getCompInit(CellTypeBubbleHeatmap);
+async function getPlotConfig(opts) {
+  const config = structuredClone(defaultConfig);
+  if (!opts.gene) throw new Error("cellTypeBubbleHeatmap requires opts.gene");
+  return copyMerge(config, opts);
+}
+function makeChartBtnMenu(holder, chartsInstance) {
+  const row = holder.append("div").style("padding", "5px");
+  row.append("span").style("font-weight", "bold").text("Enter a gene name:");
+  const geneSearch = addGeneSearchbox({
+    row,
+    genome: chartsInstance.app.opts.genome,
+    tip: new Menu({ padding: "0px" }),
+    searchOnly: "gene",
+    callback: async () => {
+      if (!geneSearch.geneSymbol) throw new Error("A valid gene selection is required");
+      chartsInstance.dom.tip.hide();
+      chartsInstance.app.dispatch({
+        type: "plot_create",
+        config: {
+          chartType: "cellTypeBubbleHeatmap",
+          gene: geneSearch.geneSymbol
+        }
+      });
+    }
+  });
+}
+export {
+  componentInit,
+  getPlotConfig,
+  makeChartBtnMenu
+};
+//# sourceMappingURL=cellTypeBubbleHeatmap-NQP7RCZO.js.map

package/dist/cellTypeBubbleHeatmap-NQP7RCZO.js.map

@@ -0,0 +1,7 @@
+{
+  "version": 3,
+  "sources": ["../plots/cellTypeBubbleHeatmap.ts"],
+  "sourcesContent": ["import type { MassState, BasePlotConfig } from '#mass/types/mass'\nimport { getCompInit, copyMerge, type RxComponent } from '#rx'\nimport { PlotBase } from './PlotBase'\nimport { Menu, addGeneSearchbox, LegendCircleReference } from '#dom'\nimport { dofetch3 } from '#common/dofetch'\nimport { scaleLinear, scaleSqrt } from 'd3'\n\nconst defaultConfig = { chartType: 'cellTypeBubbleHeatmap' }\n\nconst CELL_W = 84\nconst CELL_H = 60\nconst ROW_LABEL_W = 74\nconst GROUP_LABEL_H = 22 // cell-type group header band\nconst GENO_LABEL_H = 40 // genotype sub-label band\nconst COL_LABEL_H = GROUP_LABEL_H + GENO_LABEL_H\nconst MIN_DOT_R = 8\nconst MAX_DOT_R = 22\n// cap on \u2212log10(FDR) used for dot size so one ultra-significant (or FDR=0) dot can't\n// dwarf the rest; FDR \u2264 10^\u2212CAP all render at the max size\nconst NEG_LOG_FDR_CAP = 10\n\n// color: |log2FC| magnitude by intensity, sign by hue \u2014 blue for positive, purple\n// for negative, near-white at 0 (diverging purple\u2013white\u2013blue)\nconst COLOR_NEG = '#762a83' // purple, down-regulated (negative log2FC)\nconst COLOR_ZERO = '#f7f7f7'\nconst COLOR_POS = '#2166ac' // blue, up-regulated (positive log2FC)\n\nclass CellTypeBubbleHeatmap extends PlotBase implements RxComponent {\n\tstatic type = 'cellTypeBubbleHeatmap'\n\ttype: string\n\tdom!: { holder: any; body: any; tip: Menu; header?: any }\n\tdata: any\n\tcurrentIsoform = ''\n\tgridHolder: any\n\n\tconstructor(opts: any, api) {\n\t\tsuper(opts, api)\n\t\tthis.type = CellTypeBubbleHeatmap.type\n\t}\n\n\tasync init() {\n\t\tconst holder = this.opts.holder.append('div').style('padding', '10px')\n\t\tthis.dom = {\n\t\t\tholder,\n\t\t\tbody: holder.append('div'),\n\t\t\ttip: new Menu({ padding: '' }),\n\t\t\theader: this.opts.header\n\t\t}\n\t\tif (this.dom.header) this.dom.header.html('Cell-type Bubble Heatmap')\n\t}\n\n\tgetState(appState: MassState) {\n\t\tconst config: any = appState.plots.find((p: BasePlotConfig) => p.id === this.id)\n\t\tif (!config) throw `No plot with id='${this.id}' found`\n\t\treturn { config }\n\t}\n\n\tasync main() {\n\t\tconst gene = this.state.config?.gene\n\t\tif (!gene) throw new Error('cellTypeBubbleHeatmap: gene is missing')\n\n\t\tif (this.dom.header) this.dom.header.text(`Cell-type Bubble Heatmap: ${gene}`)\n\n\t\tconst body = {\n\t\t\tgenome: this.app.opts.state.vocab.genome,\n\t\t\tdslabel: this.app.opts.state.vocab.dslabel,\n\t\t\tgene\n\t\t}\n\n\t\tconst data = await dofetch3('termdb/cellTypeBubbleHeatmap', { body })\n\t\tif (data.error) throw data.error\n\t\tthis.data = data\n\n\t\tthis.dom.body.selectAll('*').remove()\n\n\t\tconst isoformIds = Object.keys(data.isoforms)\n\t\tif (isoformIds.length === 0) {\n\t\t\tthis.dom.body\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '20px')\n\t\t\t\t.style('color', '#666')\n\t\t\t\t.text(`No data found for gene \"${gene}\" in any cohort DAPfile.`)\n\t\t\treturn\n\t\t}\n\n\t\tthis.currentIsoform = isoformIds[0]\n\n\t\t// isoform selector\n\t\tconst isoBlock = this.dom.body.append('div').style('margin-bottom', '12px')\n\t\tisoBlock.append('span').style('font-weight', 'bold').text('Isoform: ')\n\t\tif (isoformIds.length > 1) {\n\t\t\tconst sel = isoBlock\n\t\t\t\t.append('select')\n\t\t\t\t.style('margin-left', '5px')\n\t\t\t\t.style('padding', '3px 6px')\n\t\t\t\t.on('change', () => {\n\t\t\t\t\tthis.currentIsoform = sel.node().value\n\t\t\t\t\tthis.renderGrid()\n\t\t\t\t})\n\t\t\tsel\n\t\t\t\t.selectAll('option')\n\t\t\t\t.data(isoformIds)\n\t\t\t\t.enter()\n\t\t\t\t.append('option')\n\t\t\t\t.attr('value', (d: string) => d)\n\t\t\t\t.text((d: string) => `${data.isoforms[d].gene_name} \u2014 ${d}`)\n\t\t} else {\n\t\t\tisoBlock\n\t\t\t\t.append('span')\n\t\t\t\t.style('margin-left', '5px')\n\t\t\t\t.text(`${data.isoforms[this.currentIsoform].gene_name} \u2014 ${this.currentIsoform}`)\n\t\t}\n\n\t\tthis.gridHolder = this.dom.body.append('div')\n\t\tthis.renderGrid()\n\t}\n\n\trenderGrid() {\n\t\tconst data = this.data\n\t\tconst selectedIsoform = this.currentIsoform\n\t\tconst threshold: number = data.fdrThreshold\n\n\t\tthis.gridHolder.selectAll('*').remove()\n\t\tconst container = this.gridHolder\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '24px')\n\t\t\t.style('align-items', 'flex-start')\n\t\t\t.style('flex-wrap', 'wrap')\n\n\t\tconst isoformData = data.isoforms[selectedIsoform]\n\t\tif (!isoformData) return\n\n\t\tconst columns = data.columns as { key: string; cellType: string; genotype: string }[]\n\t\tconst rows = data.rows as { key: string; label: string }[]\n\t\tconst nCols = columns.length\n\t\tconst nRows = rows.length\n\n\t\t// significance as \u2212log10(FDR), capped (guards FDR<=0 and keeps the size range sane)\n\t\tconst negLogFdr = (fdr: number): number => (fdr > 0 ? Math.min(-Math.log10(fdr), NEG_LOG_FDR_CAP) : NEG_LOG_FDR_CAP)\n\n\t\tconst cellOf = (colKey: string, rowKey: string): any => isoformData.data[colKey]?.[rowKey]\n\n\t\t// color domain = symmetric max |log2FC| across populated cells; size domain from\n\t\t// the FDR<threshold cutoff to the most-significant cell shown\n\t\tlet maxAbs = 0\n\t\tconst thresholdNegLog = negLogFdr(threshold)\n\t\tlet maxNegLog = thresholdNegLog\n\t\tfor (const col of columns) {\n\t\t\tfor (const row of rows) {\n\t\t\t\tconst s = cellOf(col.key, row.key)\n\t\t\t\tif (!s) continue\n\t\t\t\tconst v = Math.abs(s.log2FC)\n\t\t\t\tif (v > maxAbs) maxAbs = v\n\t\t\t\tconst nl = negLogFdr(s.fdr)\n\t\t\t\tif (nl > maxNegLog) maxNegLog = nl\n\t\t\t}\n\t\t}\n\t\tif (maxAbs === 0) maxAbs = 1\n\t\tif (maxNegLog <= thresholdNegLog) maxNegLog = thresholdNegLog + 1\n\n\t\tconst colorScale = scaleLinear<string>()\n\t\t\t.domain([-maxAbs, 0, maxAbs])\n\t\t\t.range([COLOR_NEG, COLOR_ZERO, COLOR_POS])\n\t\t\t.clamp(true)\n\t\t// dot size encodes significance as \u2212log10(FDR): bigger = more significant. non-significant\n\t\t// dots clamp to the smallest size and are also faded. color carries log2FC, so size and\n\t\t// color encode two independent variables.\n\t\tconst sizeScale = scaleSqrt().domain([thresholdNegLog, maxNegLog]).range([MIN_DOT_R, MAX_DOT_R]).clamp(true)\n\n\t\tconst gridW = ROW_LABEL_W + nCols * CELL_W + 20\n\t\tconst gridH = COL_LABEL_H + nRows * CELL_H + 20\n\n\t\tconst svg = container.append('svg').attr('width', gridW).attr('height', gridH).style('flex', '0 0 auto')\n\t\tconst grid = svg.append('g')\n\n\t\t// two-tier column header: cell-type group label spanning its genotype columns, then\n\t\t// the genotype label under each column\n\t\tlet c = 0\n\t\twhile (c < nCols) {\n\t\t\tconst cellType = columns[c].cellType\n\t\t\tlet end = c\n\t\t\twhile (end + 1 < nCols && columns[end + 1].cellType === cellType) end++\n\t\t\tconst xStart = ROW_LABEL_W + c * CELL_W\n\t\t\tconst xEnd = ROW_LABEL_W + (end + 1) * CELL_W\n\t\t\tconst xMid = (xStart + xEnd) / 2\n\t\t\tgrid\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', xMid)\n\t\t\t\t.attr('y', GROUP_LABEL_H - 7)\n\t\t\t\t.attr('text-anchor', 'middle')\n\t\t\t\t.attr('font-size', '13px')\n\t\t\t\t.attr('font-weight', 'bold')\n\t\t\t\t.text(cellType)\n\t\t\t// underline the group span\n\t\t\tgrid\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', xStart + 4)\n\t\t\t\t.attr('y1', GROUP_LABEL_H - 3)\n\t\t\t\t.attr('x2', xEnd - 4)\n\t\t\t\t.attr('y2', GROUP_LABEL_H - 3)\n\t\t\t\t.attr('stroke', '#bbb')\n\t\t\t\t.attr('stroke-width', 1)\n\t\t\tc = end + 1\n\t\t}\n\t\tfor (let col = 0; col < nCols; col++) {\n\t\t\tconst cx = ROW_LABEL_W + col * CELL_W + CELL_W / 2\n\t\t\tgrid\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', cx)\n\t\t\t\t.attr('y', COL_LABEL_H - 14)\n\t\t\t\t.attr('text-anchor', 'middle')\n\t\t\t\t.attr('font-size', '12px')\n\t\t\t\t.attr('font-weight', '600')\n\t\t\t\t.text(columns[col].genotype)\n\t\t}\n\n\t\t// row labels (timepoints)\n\t\tfor (let r = 0; r < nRows; r++) {\n\t\t\tconst cy = COL_LABEL_H + r * CELL_H + CELL_H / 2\n\t\t\tgrid\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', ROW_LABEL_W - 12)\n\t\t\t\t.attr('y', cy)\n\t\t\t\t.attr('text-anchor', 'end')\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.attr('font-size', '13px')\n\t\t\t\t.attr('font-weight', 'bold')\n\t\t\t\t.text(rows[r].label)\n\t\t}\n\n\t\t// cells: outline + one dot when populated\n\t\tfor (let r = 0; r < nRows; r++) {\n\t\t\tfor (let col = 0; col < nCols; col++) {\n\t\t\t\tconst x0 = ROW_LABEL_W + col * CELL_W\n\t\t\t\tconst y0 = COL_LABEL_H + r * CELL_H\n\n\t\t\t\tgrid\n\t\t\t\t\t.append('rect')\n\t\t\t\t\t.attr('x', x0)\n\t\t\t\t\t.attr('y', y0)\n\t\t\t\t\t.attr('width', CELL_W)\n\t\t\t\t\t.attr('height', CELL_H)\n\t\t\t\t\t.attr('fill', 'none')\n\t\t\t\t\t.attr('stroke', '#eee')\n\t\t\t\t\t.attr('stroke-width', 1)\n\n\t\t\t\tconst s = cellOf(columns[col].key, rows[r].key)\n\t\t\t\tif (!s) continue\n\n\t\t\t\tconst cx = x0 + CELL_W / 2\n\t\t\t\tconst cy = y0 + CELL_H / 2\n\t\t\t\tgrid\n\t\t\t\t\t.append('circle')\n\t\t\t\t\t.attr('cx', cx)\n\t\t\t\t\t.attr('cy', cy)\n\t\t\t\t\t.attr('r', sizeScale(negLogFdr(s.fdr)))\n\t\t\t\t\t.attr('fill', colorScale(s.log2FC))\n\t\t\t\t\t.attr('stroke', '#888')\n\t\t\t\t\t.attr('stroke-width', 0.8)\n\t\t\t\t\t.style('opacity', s.significant ? 1 : 0.35)\n\t\t\t\t\t.on('mouseover', (event: MouseEvent) =>\n\t\t\t\t\t\tthis.showCellTip(event, isoformData.gene_name, selectedIsoform, columns[col], rows[r], s)\n\t\t\t\t\t)\n\t\t\t\t\t.on('mouseout', () => this.dom.tip.hide())\n\t\t\t}\n\t\t}\n\n\t\tthis.renderLegend(container, colorScale, maxAbs, threshold, maxNegLog)\n\t}\n\n\tprivate fmtFdr(v: number): string {\n\t\treturn v >= 0.0001 ? v.toFixed(4) : v.toExponential(2)\n\t}\n\n\tprivate showCellTip(\n\t\tevent: MouseEvent,\n\t\tgeneName: string,\n\t\tisoform: string,\n\t\tcol: { cellType: string; genotype: string },\n\t\trow: { label: string },\n\t\ts: any\n\t) {\n\t\tthis.dom.tip.clear().show(event.clientX, event.clientY)\n\t\tconst t = this.dom.tip.d.append('div').style('padding', '8px').style('font-size', '13px')\n\t\tt.append('div').style('font-weight', 'bold').style('margin-bottom', '4px').text(`${geneName} \u2014 ${isoform}`)\n\t\tt.append('div').text(`Cell type: ${col.cellType}`)\n\t\tt.append('div').text(`Genotype: ${col.genotype}`)\n\t\tt.append('div').text(`Timepoint: ${row.label}`)\n\t\tt.append('div').text(`Protein: ${s.id}`)\n\t\tt.append('div').text(`log\u2082FC: ${s.log2FC.toFixed(3)}`)\n\t\tt.append('div').text(`FDR: ${this.fmtFdr(s.fdr)}${s.significant ? '' : ' (n.s.)'}`)\n\t\tt.append('div')\n\t\t\t.style('color', '#666')\n\t\t\t.style('margin-top', '4px')\n\t\t\t.text('Color = log\u2082FC (blue up / purple down). Size = \u2212log\u2081\u2080 FDR.')\n\t}\n\n\tprivate renderLegend(container: any, colorScale: any, maxAbs: number, threshold: number, maxNegLog: number) {\n\t\tconst legend = container\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('flex-direction', 'column')\n\t\t\t.style('gap', '16px')\n\t\t\t.style('padding', '8px 0')\n\t\t\t.style('min-width', '180px')\n\t\t\t.style('max-width', '260px')\n\n\t\t// color scale\n\t\tconst colorBlock = legend.append('div')\n\t\tcolorBlock\n\t\t\t.append('div')\n\t\t\t.style('font-weight', 'bold')\n\t\t\t.style('font-size', '13px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.text('log\u2082FC')\n\t\tconst cW = 22\n\t\tconst cH = 130\n\t\tconst cSvg = colorBlock\n\t\t\t.append('svg')\n\t\t\t.attr('width', cW + 80)\n\t\t\t.attr('height', cH + 16)\n\t\tconst gid = `ctbh-grad-${this.id}`\n\t\tconst grad = cSvg\n\t\t\t.append('defs')\n\t\t\t.append('linearGradient')\n\t\t\t.attr('id', gid)\n\t\t\t.attr('x1', '0')\n\t\t\t.attr('y1', '0')\n\t\t\t.attr('x2', '0')\n\t\t\t.attr('y2', '1')\n\t\tconst steps = 10\n\t\tfor (let i = 0; i <= steps; i++) {\n\t\t\tconst t = i / steps\n\t\t\t// top = +maxAbs (blue), bottom = \u2212maxAbs (purple)\n\t\t\tgrad\n\t\t\t\t.append('stop')\n\t\t\t\t.attr('offset', `${t * 100}%`)\n\t\t\t\t.attr('stop-color', colorScale(maxAbs * (1 - 2 * t)))\n\t\t}\n\t\tcSvg\n\t\t\t.append('rect')\n\t\t\t.attr('x', 0)\n\t\t\t.attr('y', 8)\n\t\t\t.attr('width', cW)\n\t\t\t.attr('height', cH)\n\t\t\t.style('fill', `url(#${gid})`)\n\t\t\t.attr('stroke', '#999')\n\t\tconst cScale = scaleLinear()\n\t\t\t.domain([maxAbs, -maxAbs])\n\t\t\t.range([8, cH + 8])\n\t\tfor (const tick of [maxAbs, maxAbs / 2, 0, -maxAbs / 2, -maxAbs]) {\n\t\t\tconst y = cScale(tick)\n\t\t\tcSvg\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', cW)\n\t\t\t\t.attr('y1', y)\n\t\t\t\t.attr('x2', cW + 5)\n\t\t\t\t.attr('y2', y)\n\t\t\t\t.attr('stroke', '#666')\n\t\t\tcSvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', cW + 8)\n\t\t\t\t.attr('y', y)\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.attr('font-size', '10px')\n\t\t\t\t.text(`${tick > 0 ? '+' : ''}${tick.toFixed(2)}`)\n\t\t}\n\t\tcolorBlock\n\t\t\t.append('div')\n\t\t\t.style('font-size', '11px')\n\t\t\t.style('color', '#666')\n\t\t\t.style('margin-top', '2px')\n\t\t\t.text('blue = up (+), purple = down (\u2212)')\n\n\t\t// size key \u2014 significance (\u2212log10 FDR)\n\t\tconst sizeBlock = legend.append('div')\n\t\tsizeBlock\n\t\t\t.append('div')\n\t\t\t.style('font-weight', 'bold')\n\t\t\t.style('font-size', '13px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.text('Dot size: significance (\u2212log\u2081\u2080 FDR)')\n\t\tconst sSvg = sizeBlock.append('svg')\n\t\tconst sG = sSvg.append('g')\n\t\tnew LegendCircleReference({\n\t\t\tg: sG,\n\t\t\tinputMin: 0,\n\t\t\tinputMax: MAX_DOT_R * 2,\n\t\t\tminRadius: MIN_DOT_R,\n\t\t\tmaxRadius: MAX_DOT_R,\n\t\t\tminLabel: Number(Math.min(-Math.log10(threshold), NEG_LOG_FDR_CAP).toFixed(1)),\n\t\t\tmaxLabel: Number(maxNegLog.toFixed(1))\n\t\t})\n\t\tconst sPad = 4\n\t\tconst sBox = sG.node().getBBox()\n\t\tsG.attr('transform', `translate(${sPad - sBox.x}, ${sPad - sBox.y})`)\n\t\tsSvg.attr('width', Math.ceil(sBox.width + 2 * sPad)).attr('height', Math.ceil(sBox.height + 2 * sPad))\n\n\t\tconst notes = legend\n\t\t\t.append('div')\n\t\t\t.style('font-size', '11px')\n\t\t\t.style('color', '#666')\n\t\t\t.style('line-height', '1.5')\n\t\t\t.style('max-width', '240px')\n\t\t\t.style('overflow-wrap', 'break-word')\n\t\tnotes\n\t\t\t.append('div')\n\t\t\t.text(\n\t\t\t\t`Color = log\u2082FC (blue up, purple down). Dot size = significance, \u2212log\u2081\u2080 FDR; the smallest size marks the FDR < ${threshold} cutoff. Non-significant dots (FDR \u2265 ${threshold}) are faded.`\n\t\t\t)\n\t\tnotes\n\t\t\t.append('div')\n\t\t\t.style('margin-top', '4px')\n\t\t\t.text('An empty cell means the cohort was not assayed (e.g. OPC has no 4m) or the protein was not detected.')\n\t}\n}\n\nexport const componentInit = getCompInit(CellTypeBubbleHeatmap)\n\nexport async function getPlotConfig(opts: any) {\n\tconst config = structuredClone(defaultConfig)\n\tif (!opts.gene) throw new Error('cellTypeBubbleHeatmap requires opts.gene')\n\treturn copyMerge(config, opts)\n}\n\nexport function makeChartBtnMenu(holder: any, chartsInstance: any) {\n\tconst row = holder.append('div').style('padding', '5px')\n\trow.append('span').style('font-weight', 'bold').text('Enter a gene name:')\n\n\tconst geneSearch = addGeneSearchbox({\n\t\trow,\n\t\tgenome: chartsInstance.app.opts.genome,\n\t\ttip: new Menu({ padding: '0px' }),\n\t\tsearchOnly: 'gene',\n\t\tcallback: async () => {\n\t\t\tif (!geneSearch.geneSymbol) throw new Error('A valid gene selection is required')\n\t\t\tchartsInstance.dom.tip.hide()\n\t\t\tchartsInstance.app.dispatch({\n\t\t\t\ttype: 'plot_create',\n\t\t\t\tconfig: {\n\t\t\t\t\tchartType: 'cellTypeBubbleHeatmap',\n\t\t\t\t\tgene: geneSearch.geneSymbol\n\t\t\t\t}\n\t\t\t})\n\t\t}\n\t})\n}\n"],
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