@sjcrh/proteinpaint-client 2.193.0 → 2.195.0

package/dist/proteinView-7FDCILPH.js.map

@@ -1,7 +0,0 @@
-{
-  "version": 3,
-  "sources": ["../plots/brainRegions.samples.ts", "../plots/proteinView.ts"],
-  "sourcesContent": ["import type { Menu } from '#dom'\nimport { scaleSequential, interpolateBlues, scaleLinear } from 'd3'\nimport { loadBrainAssets, renderBrainSvg } from './brainRegions.svg'\n\nconst NO_DATA_COLOR = '#dcdcdc'\nconst BRAIN_RENDER_W = 440\n\n// Monotonic counter for unique <linearGradient> ids (Date.now() can collide when the\n// brain re-renders within the same millisecond on volcano changes).\nlet gradientSeq = 0\n\nexport type BrainRegionSamplesOpts = {\n\t/** region code \u2192 display name */\n\tregions: { [code: string]: string }\n\t/** region code \u2192 sample count (case + control) */\n\tcounts: { [code: string]: number }\n\ttemplateUrl: string\n\tsvgUrl: string\n\t/** total distinct samples behind the counts; shown in the title */\n\ttotalSamples: number\n\ttip: Menu\n\t/** number of samples whose region value wasn't a configured region */\n\tunmappedCount?: number\n\t/** invoked when a region is clicked (e.g. the Protein View volcano sync) */\n\tonRegionClick?: (code: string, event: MouseEvent) => void\n\t/** when true for a code, render that region as filtered-out */\n\tisRegionDimmed?: (code: string) => boolean\n}\n\n// Render the brain \"sample distribution\" view: each region filled by its sample\n// count (sequential blues) with a samples-per-region legend. Kept as a standalone\n// renderer (not a plot component) so Protein View \u2014 and future callers \u2014 can embed\n// it next to the cohort volcano.\nexport async function drawBrainRegionSamples(holder: any, opts: BrainRegionSamplesOpts) {\n\tconst { regions, counts, templateUrl, svgUrl, totalSamples, tip } = opts\n\tconst assets = await loadBrainAssets(svgUrl, Object.keys(regions))\n\t// Title is built live from totalSamples (case + control) so it stays correct as\n\t// cohorts/regions are hidden.\n\tconst title = `All samples (n=${totalSamples})`\n\tconst max = Math.max(0, ...Object.values(counts))\n\tconst colorScale = scaleSequential(interpolateBlues).domain([0, Math.max(1, max)])\n\n\tconst container = holder\n\t\t.append('div')\n\t\t.attr('class', 'sjpp-brain-region-samples-container')\n\t\t.style('display', 'flex')\n\t\t.style('gap', '20px')\n\t\t.style('flex-wrap', 'wrap')\n\t\t.style('align-items', 'flex-start')\n\n\trenderBrainSvg({\n\t\tholder: container,\n\t\twidth: BRAIN_RENDER_W,\n\t\ttemplateUrl,\n\t\tassets,\n\t\tregions,\n\t\ttip,\n\t\ttitle,\n\t\tfillByRegion: (code: string) => {\n\t\t\tconst n = counts[code] ?? 0\n\t\t\treturn n > 0 ? (colorScale(n) as string) : NO_DATA_COLOR\n\t\t},\n\t\ttooltipByRegion: (code: string, label: string) => {\n\t\t\tconst n = counts[code] ?? 0\n\t\t\treturn `${label} (${code})\\nSamples: ${n}`\n\t\t},\n\t\tonRegionClick: opts.onRegionClick,\n\t\tisRegionDimmed: opts.isRegionDimmed\n\t})\n\n\trenderSamplesLegend(container, colorScale, max)\n\n\tconst unmappedCount = opts.unmappedCount ?? 0\n\tif (unmappedCount > 0) {\n\t\tholder\n\t\t\t.append('div')\n\t\t\t.style('margin-top', '4px')\n\t\t\t.style('width', `${BRAIN_RENDER_W}px`)\n\t\t\t.style('text-align', 'right')\n\t\t\t.style('font-size', '11px')\n\t\t\t.style('color', '#888')\n\t\t\t.text(`${unmappedCount} sample${unmappedCount === 1 ? '' : 's'} had unmapped region values`)\n\t}\n}\n\nfunction renderSamplesLegend(container: any, colorScale: any, max: number) {\n\tconst legendDiv = container\n\t\t.append('div')\n\t\t.style('display', 'flex')\n\t\t.style('flex-direction', 'column')\n\t\t.style('justify-content', 'center')\n\t\t.style('padding', '10px')\n\n\tlegendDiv\n\t\t.append('div')\n\t\t.style('font-weight', 'bold')\n\t\t.style('font-size', '13px')\n\t\t.style('margin-bottom', '8px')\n\t\t.text('Samples per region')\n\n\tconst legendWidth = 20\n\tconst legendHeight = 200\n\tconst svg = legendDiv\n\t\t.append('svg')\n\t\t.attr('width', legendWidth + 60)\n\t\t.attr('height', legendHeight + 30)\n\n\tconst defs = svg.append('defs')\n\tconst gradientId = `brain-samples-gradient-${gradientSeq++}`\n\tconst gradient = defs\n\t\t.append('linearGradient')\n\t\t.attr('id', gradientId)\n\t\t.attr('x1', '0')\n\t\t.attr('y1', '0')\n\t\t.attr('x2', '0')\n\t\t.attr('y2', '1')\n\n\t// Gradient is drawn high (max) \u2192 low (0), so y1=0 takes color at max.\n\tconst steps = 10\n\tfor (let i = 0; i <= steps; i++) {\n\t\tconst t = i / steps\n\t\tconst val = max * (1 - t)\n\t\tgradient\n\t\t\t.append('stop')\n\t\t\t.attr('offset', `${t * 100}%`)\n\t\t\t.attr('stop-color', colorScale(val))\n\t}\n\n\tsvg\n\t\t.append('rect')\n\t\t.attr('x', 0)\n\t\t.attr('y', 10)\n\t\t.attr('width', legendWidth)\n\t\t.attr('height', legendHeight)\n\t\t.style('fill', `url(#${gradientId})`)\n\t\t.attr('stroke', '#999')\n\n\tconst legendScale = scaleLinear()\n\t\t.domain([max, 0])\n\t\t.range([10, legendHeight + 10])\n\tconst ticks = max > 0 ? [max, Math.round((max * 3) / 4), Math.round(max / 2), Math.round(max / 4), 0] : [0]\n\tfor (const tick of ticks) {\n\t\tconst y = legendScale(tick)\n\t\tsvg\n\t\t\t.append('line')\n\t\t\t.attr('x1', legendWidth)\n\t\t\t.attr('y1', y)\n\t\t\t.attr('x2', legendWidth + 5)\n\t\t\t.attr('y2', y)\n\t\t\t.attr('stroke', '#666')\n\t\tsvg\n\t\t\t.append('text')\n\t\t\t.attr('x', legendWidth + 8)\n\t\t\t.attr('y', y)\n\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t.attr('font-size', '10px')\n\t\t\t.text(String(tick))\n\t}\n\n\tlegendDiv\n\t\t.append('div')\n\t\t.style('margin-top', '10px')\n\t\t.style('font-size', '12px')\n\t\t.style('color', '#666')\n\t\t.html(\n\t\t\t`<span style=\"display:inline-block;width:14px;height:14px;background:${NO_DATA_COLOR};border:1px solid #999;vertical-align:middle;margin-right:4px\"></span> No samples`\n\t\t)\n}\n", "import type { MassState, BasePlotConfig } from '#mass/types/mass'\nimport { getCompInit, copyMerge, type RxComponent } from '#rx'\nimport { axisstyle, to_svg } from '#src/client'\nimport { Menu, table2col, LegendCircleReference, addGeneSearchbox, DataPointInteractions, make_radios } from '#dom'\nimport { PlotBase } from './PlotBase'\nimport { dofetch3 } from '#common/dofetch'\nimport { drawBrainRegionSamples } from './brainRegions.samples'\nimport { axisBottom, axisLeft, scaleLinear, rgb, select, creator } from 'd3'\nimport { shapeSelector, shapes } from '../dom/shapes.js'\nimport { NumericModes, TermTypes } from '#shared/terms.js'\nimport { aa2gmcoord } from '#src/coord'\nimport { mclass, getColors } from '#shared/common.js'\nimport { roundValue } from '#shared/roundValue.js'\nimport { icons as controlIcons } from '../dom/control.icons'\n\nconst defaultConfig = {\n\tchartType: 'proteinView'\n}\n\n// Cohort volcano hover/hit-test tuning. Kept together so they're easy to find\n// and adjust as a group when the dot styling changes.\nconst COHORT_VOLCANO_HIT_RADIUS_PADDING_PX = 3 // px added to maxDotRadius for the quadtree broad-query\nconst COHORT_VOLCANO_HIT_BUFFER_PX = 2 // px of forgiveness around each dot's own visual edge\nconst COHORT_VOLCANO_HOVER_RING_SIZE_SCALE = 1.15 // hover ring grows the dot by this factor\nconst COHORT_VOLCANO_HOVER_RING_STROKE_PX = 1.5 // hover ring stroke width (non-scaling)\nconst COHORT_VOLCANO_HOVER_MAX_COHORTS = 5 // max rows shown in the hover tooltip table; rest collapse into \"and N more...\"\n\nclass ProteinView extends PlotBase implements RxComponent {\n\tstatic type = 'proteinView'\n\ttype: string\n\tdom!: {\n\t\tholder: any\n\t\tbody: any\n\t\ttip: Menu\n\t\theader?: any\n\t}\n\tcomponents: any\n\n\tconstructor(opts: any, api) {\n\t\tsuper(opts, api)\n\t\tthis.type = ProteinView.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('Protein View')\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\tmaySetSandboxHeader() {\n\t\tif (!this.dom.header) return\n\t\tconst term = this.state.config?.tw?.term\n\t\tconst header = `Protein View: ${term?.name}`\n\t\tthis.dom.header.text(header)\n\t}\n\n\tasync main() {\n\t\tconst term = this.state.config?.tw?.term\n\t\tif (!term?.name) throw new Error('proteinView: selected protein term is missing')\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\tterm: this.state.config.tw,\n\t\t\tfilter: this.state.config.filter,\n\t\t\tfilter0: this.state.config.filter0\n\t\t}\n\n\t\tthis.maySetSandboxHeader()\n\t\tconst data = await dofetch3('termdb/proteome', { body })\n\t\tif (data.error) throw data.error\n\t\tthis.dom.body.selectAll('*').remove()\n\n\t\tconst topRow = this.dom.body\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '16px')\n\t\t\t.style('align-items', 'flex-start')\n\t\t\t.style('flex-wrap', 'wrap')\n\t\tconst volcanoApi = renderCohortVolcano(topRow, data, this)\n\n\t\tconst termdbConfig = this.app.vocabApi.termdbConfig\n\t\tif (termdbConfig?.queries?.proteome?.brainRegions) {\n\t\t\tawait renderBrainRegionSamplesPanel(topRow, data, this, volcanoApi)\n\t\t}\n\n\t\t// group PTM cohorts by organism first, then isoform.\n\t\tconst ptmDataByOrganism = new Map<string, Map<string, any[]>>()\n\t\tfor (const cohortData of data.cohorts || []) {\n\t\t\tif (!cohortData.PTMType) continue // filter out non-PTM cohorts\n\t\t\tconst organism = cohortData.organism\n\t\t\tconst isoform = cohortData.isoform\n\t\t\tconst ptmDataByIsoform = ptmDataByOrganism.get(organism) || new Map<string, any[]>()\n\t\t\tptmDataByOrganism.set(organism, ptmDataByIsoform)\n\t\t\tconst existingCohorts = ptmDataByIsoform.get(isoform)\n\t\t\tif (!existingCohorts) {\n\t\t\t\tptmDataByIsoform.set(isoform, [cohortData])\n\t\t\t} else {\n\t\t\t\texistingCohorts.push(cohortData)\n\t\t\t}\n\t\t}\n\n\t\ttype LollipopSection = { organism: string; isoform: string; cohorts: any[]; genomeName: string }\n\t\tconst sections: LollipopSection[] = []\n\t\tfor (const [organism, byIso] of ptmDataByOrganism) {\n\t\t\tfor (const [isoform, cohorts] of byIso) {\n\t\t\t\tsections.push({ organism, isoform, cohorts, genomeName: cohorts[0].genomeName })\n\t\t\t}\n\t\t}\n\t\tif (sections.length === 0) return\n\n\t\tlet allGenomes: any = null\n\t\tconst baseGenome = this.app.opts.genome\n\t\tconst getGenome = async (genomeName: string) => {\n\t\t\tif (genomeName === baseGenome.name) return baseGenome\n\t\t\tif (!allGenomes) {\n\t\t\t\tconst result = await dofetch3('genomes')\n\t\t\t\tallGenomes = result.genomes || {}\n\t\t\t\tfor (const g of Object.values(allGenomes) as any[]) {\n\t\t\t\t\tif (g.chrlookup || g.name == baseGenome.name) continue\n\t\t\t\t\tg.chrlookup = {}\n\t\t\t\t\tfor (const chr in g.majorchr) {\n\t\t\t\t\t\tg.chrlookup[chr.toUpperCase()] = { name: chr, len: g.majorchr[chr], major: true }\n\t\t\t\t\t}\n\t\t\t\t\tfor (const chr in g.minorchr || {}) {\n\t\t\t\t\t\tg.chrlookup[chr.toUpperCase()] = { name: chr, len: g.minorchr[chr] }\n\t\t\t\t\t}\n\t\t\t\t}\n\t\t\t}\n\t\t\tconst g = allGenomes[genomeName]\n\t\t\tif (!g) throw `genome ${genomeName} not supported`\n\t\t\treturn g\n\t\t}\n\n\t\tif (sections.length === 1) {\n\t\t\tconst s = sections[0]\n\t\t\tconst genome = await getGenome(s.genomeName)\n\t\t\tawait renderPTMLollipop(this.dom.body.append('div'), s.cohorts, this, s.isoform, genome)\n\t\t\treturn\n\t\t}\n\n\t\tconst keyOf = (s: LollipopSection) => `${s.organism}\\u0001${s.isoform}`\n\t\tconst selectedKeys = new Set<string>([keyOf(sections[0])])\n\t\tlet compareMode = false\n\n\t\tconst layoutDiv = this.dom.body\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '16px')\n\t\t\t.style('margin-top', '10px')\n\t\t\t.style('margin-left', '70px')\n\t\t\t.style('align-items', 'flex-start')\n\t\tconst sidebar = layoutDiv\n\t\t\t.append('div')\n\t\t\t.style('flex', '0 0 220px')\n\t\t\t.style('border', '1px solid #e5e7eb')\n\t\t\t.style('border-radius', '4px')\n\t\t\t.style('padding', '8px')\n\t\t\t.style('font-size', '.85em')\n\t\t\t.style('position', 'sticky')\n\t\t\t.style('top', '8px')\n\t\t\t.style('margin-top', '20px')\n\t\t\t.style('max-height', '85vh')\n\t\t\t.style('overflow', 'auto')\n\t\tconst rightPane = layoutDiv.append('div').style('flex', '1 1 auto').style('min-width', '0')\n\n\t\tconst sidebarHeader = sidebar\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', '6px')\n\t\t\t.style('margin-bottom', '8px')\n\t\tsidebarHeader\n\t\t\t.append('span')\n\t\t\t.style('font-weight', '600')\n\t\t\t.style('font-size', '1.5em')\n\t\t\t.style('text-transform', 'uppercase')\n\t\t\t.text('Isoforms')\n\n\t\tconst modeToggle = sidebarHeader\n\t\t\t.append('div')\n\t\t\t.style('display', 'inline-flex')\n\t\t\t.style('align-items', 'center')\n\t\t\t.style('gap', '6px')\n\t\tmodeToggle.append('span').style('color', '#6b7280').text('Mode:')\n\t\tmake_radios({\n\t\t\tholder: modeToggle.append('div').attr('aria-label', 'Isoform view mode'),\n\t\t\toptions: [\n\t\t\t\t{ label: 'Single', value: 'single', checked: true },\n\t\t\t\t{ label: 'Compare', value: 'compare' }\n\t\t\t],\n\t\t\tstyles: { display: 'inline-block' },\n\t\t\tcallback: (value: string) => {\n\t\t\t\tconst asCompare = value === 'compare'\n\t\t\t\tif (asCompare === compareMode) return\n\t\t\t\tcompareMode = asCompare\n\t\t\t\tif (!compareMode && selectedKeys.size > 1) {\n\t\t\t\t\tconst first = selectedKeys.values().next().value as string\n\t\t\t\t\tselectedKeys.clear()\n\t\t\t\t\tselectedKeys.add(first)\n\t\t\t\t}\n\t\t\t\trenderSidebar()\n\t\t\t\tvoid renderRight()\n\t\t\t}\n\t\t})\n\n\t\tconst sidebarList = sidebar.append('div')\n\t\tconst sectionsByOrganism = new Map<string, LollipopSection[]>()\n\t\tfor (const s of sections) {\n\t\t\tconst arr = sectionsByOrganism.get(s.organism) || []\n\t\t\tarr.push(s)\n\t\t\tsectionsByOrganism.set(s.organism, arr)\n\t\t}\n\t\tconst showOrganismHeading = sectionsByOrganism.size > 1\n\n\t\tconst renderSidebar = () => {\n\t\t\tsidebarList.selectAll('*').remove()\n\t\t\tfor (const [organism, items] of sectionsByOrganism) {\n\t\t\t\tif (showOrganismHeading) {\n\t\t\t\t\tsidebarList\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.text(organism)\n\t\t\t\t\t\t.style('font-weight', '600')\n\t\t\t\t\t\t.style('color', '#374151')\n\t\t\t\t\t\t.style('margin', '6px 0 4px 0')\n\t\t\t\t}\n\t\t\t\tfor (const s of items) {\n\t\t\t\t\tconst key = keyOf(s)\n\t\t\t\t\tconst isSelected = selectedKeys.has(key)\n\t\t\t\t\tconst isSoleSelection = isSelected && selectedKeys.size === 1\n\t\t\t\t\tconst toggleSelection = () => {\n\t\t\t\t\t\tif (compareMode) {\n\t\t\t\t\t\t\tif (selectedKeys.has(key)) {\n\t\t\t\t\t\t\t\tif (selectedKeys.size > 1) selectedKeys.delete(key)\n\t\t\t\t\t\t\t\telse return // keep at least one\n\t\t\t\t\t\t\t} else selectedKeys.add(key)\n\t\t\t\t\t\t} else {\n\t\t\t\t\t\t\tif (selectedKeys.has(key) && selectedKeys.size === 1) return\n\t\t\t\t\t\t\tselectedKeys.clear()\n\t\t\t\t\t\t\tselectedKeys.add(key)\n\t\t\t\t\t\t}\n\t\t\t\t\t\trenderSidebar()\n\t\t\t\t\t\tvoid renderRight()\n\t\t\t\t\t}\n\t\t\t\t\tconst row = sidebarList\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.attr('role', compareMode ? 'checkbox' : 'radio')\n\t\t\t\t\t\t.attr('aria-checked', String(isSelected))\n\t\t\t\t\t\t.attr('aria-label', `${s.organism} ${s.isoform}`)\n\t\t\t\t\t\t.attr('tabindex', '0')\n\t\t\t\t\t\t.style('display', 'flex')\n\t\t\t\t\t\t.style('align-items', 'center')\n\t\t\t\t\t\t.style('gap', '6px')\n\t\t\t\t\t\t.style('padding', '3px 4px')\n\t\t\t\t\t\t.style('border-radius', '3px')\n\t\t\t\t\t\t.style('background', isSelected ? '#eff6ff' : 'transparent')\n\t\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t\t.on('click', toggleSelection)\n\t\t\t\t\t\t.on('keydown', (event: KeyboardEvent) => {\n\t\t\t\t\t\t\tif (event.key === 'Enter' || event.key === ' ') {\n\t\t\t\t\t\t\t\tevent.preventDefault()\n\t\t\t\t\t\t\t\ttoggleSelection()\n\t\t\t\t\t\t\t}\n\t\t\t\t\t\t})\n\t\t\t\t\tif (compareMode) {\n\t\t\t\t\t\trow\n\t\t\t\t\t\t\t.append('input')\n\t\t\t\t\t\t\t.attr('type', 'checkbox')\n\t\t\t\t\t\t\t.attr('tabindex', '-1')\n\t\t\t\t\t\t\t.attr('aria-hidden', 'true')\n\t\t\t\t\t\t\t.property('checked', isSelected)\n\t\t\t\t\t\t\t.property('disabled', isSoleSelection)\n\t\t\t\t\t\t\t.style('margin', '0')\n\t\t\t\t\t\t\t.style('cursor', isSoleSelection ? 'not-allowed' : 'pointer')\n\t\t\t\t\t\t\t.on('click', (event: Event) => {\n\t\t\t\t\t\t\t\tevent.stopPropagation()\n\t\t\t\t\t\t\t\ttoggleSelection()\n\t\t\t\t\t\t\t})\n\t\t\t\t\t}\n\t\t\t\t\trow.append('span').text(s.isoform)\n\t\t\t\t\trow.append('span').style('color', '#6b7280').style('margin-left', 'auto').text(String(s.cohorts.length))\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\tconst renderRight = async () => {\n\t\t\trightPane.selectAll('*').remove()\n\t\t\tconst selected = sections.filter(s => selectedKeys.has(keyOf(s)))\n\t\t\tif (!selected.length) return\n\t\t\tconst cols = rightPane\n\t\t\t\t.append('div')\n\t\t\t\t.style('display', 'flex')\n\t\t\t\t.style('flex-direction', 'column')\n\t\t\t\t.style('gap', '16px')\n\t\t\tfor (const s of selected) {\n\t\t\t\tconst col = cols.append('div').style('min-width', '0')\n\t\t\t\ttry {\n\t\t\t\t\tconst genome = await getGenome(s.genomeName)\n\t\t\t\t\tawait renderPTMLollipop(col, s.cohorts, this, s.isoform, genome)\n\t\t\t\t} catch (err: any) {\n\t\t\t\t\tcol\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.style('color', '#b91c1c')\n\t\t\t\t\t\t.style('padding', '6px')\n\t\t\t\t\t\t.text(`Failed to render ${s.organism} \u00B7 ${s.isoform}: ${err?.message || err}`)\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\trenderSidebar()\n\t\tawait renderRight()\n\t}\n}\n\n// Draws the brain \"sample distribution\" panel next to the cohort volcano, kept in\n// sync with it: the brain counts the exact samples the visible volcano dots represent,\n// and clicking a region hides the dots whose samples fall only in hidden regions.\nasync function renderBrainRegionSamplesPanel(holder: any, data: any, self: ProteinView, volcanoApi: VolcanoApi) {\n\tconst brConfig = self.app.vocabApi.termdbConfig?.queries?.proteome?.brainRegions\n\tif (!brConfig?.regions) return\n\tconst regions: { [code: string]: string } = brConfig.regions\n\tconst allRegionCodes = Object.keys(regions)\n\t// Global sample-id \u2192 region-code map (deduped, sent once by the proteome route).\n\tconst sampleRegionById: { [sid: string]: string } = data?.sampleRegions || {}\n\n\t// Each volcano dot is a proteome cohort entry carrying its own sample ids; a\n\t// sample's region is looked up in sampleRegionById. Driving the brain from these\n\t// (instead of a separate endpoint) makes the brain's counts match the volcano exactly.\n\tconst allDots: any[] = (data?.cohorts || []).filter((d: any) => Array.isArray(d.sampleIds) && d.sampleIds.length)\n\tif (!allDots.length) return\n\n\t// Created lazily on the first redraw so a stub volcano (no valid dots, hence no\n\t// visibility callback) doesn't leave an empty panel div behind.\n\tlet panel: any\n\n\t// Sentinel for samples that carry no configured brain-region annotation. Held\n\t// in hiddenRegions only by \"Show only\" (and cleared by \"Show all\"), so a dot\n\t// made up of unannotated samples is hidden when isolating a single region but\n\t// stays visible under a plain per-region Hide.\n\tconst NO_REGION = '__no_region__'\n\n\tconst hiddenRegions = new Set<string>()\n\t// Overwritten by the immediate onVisibilityChange fire below, before the first redraw.\n\tlet visibleDots: any[] = []\n\n\t// Count DISTINCT samples (case + control) per region across the given dots.\n\t// Distinct is required because isoform dots of one cohort share samples.\n\t// unmappedCount = distinct samples whose region isn't one of the configured\n\t// regions (so they're absent from the brain), surfaced as a legend note.\n\tconst countFromDots = (dotList: any[]) => {\n\t\tconst seen = new Set<string>()\n\t\tconst counts: { [code: string]: number } = {}\n\t\tfor (const code of allRegionCodes) counts[code] = 0\n\t\tlet totalSamples = 0\n\t\tfor (const dot of dotList) {\n\t\t\tfor (const sid of dot.sampleIds) {\n\t\t\t\tif (seen.has(sid)) continue\n\t\t\t\tseen.add(sid)\n\t\t\t\tconst code = sampleRegionById[sid]\n\t\t\t\tif (code && counts[code] !== undefined) {\n\t\t\t\t\tcounts[code]++\n\t\t\t\t\ttotalSamples++\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\t\treturn { counts, totalSamples, unmappedCount: seen.size - totalSamples }\n\t}\n\n\t// A cohort is hidden if every region its samples occupy is hidden. Collect\n\t// those cohort names to drive the volcano's external hide (the volcano hides\n\t// by cohort name). Region-pinned cohorts map to a single region, so hiding a\n\t// region hides exactly its cohorts.\n\tconst deriveHiddenCohorts = (): Set<string> => {\n\t\tconst hidden = new Set<string>()\n\t\tif (!hiddenRegions.size) return hidden\n\t\tconst regionsByCohort = new Map<string, Set<string>>()\n\t\tfor (const dot of allDots) {\n\t\t\tconst set = regionsByCohort.get(dot.cohortName) || new Set<string>()\n\t\t\tfor (const sid of dot.sampleIds) {\n\t\t\t\t// unannotated samples count as NO_REGION so \"Show only\" can hide them.\n\t\t\t\tset.add(sampleRegionById[sid] || NO_REGION)\n\t\t\t}\n\t\t\tregionsByCohort.set(dot.cohortName, set)\n\t\t}\n\t\tfor (const [cohort, set] of regionsByCohort) {\n\t\t\tif (!set.size) continue\n\t\t\tlet allHidden = true\n\t\t\tfor (const code of set) {\n\t\t\t\tif (!hiddenRegions.has(code)) {\n\t\t\t\t\tallHidden = false\n\t\t\t\t\tbreak\n\t\t\t\t}\n\t\t\t}\n\t\t\tif (allHidden) hidden.add(cohort)\n\t\t}\n\t\treturn hidden\n\t}\n\n\t// Separate Menu so the click popup doesn't fight with hover tooltips.\n\tconst regionMenu = new Menu({ padding: '0px' })\n\n\tconst applyHiddenRegions = () => {\n\t\tvolcanoApi.setExternallyHiddenCohorts(deriveHiddenCohorts())\n\t}\n\n\tconst openRegionMenu = (code: string, event: MouseEvent) => {\n\t\tself.dom.tip.hide()\n\t\tregionMenu.clear()\n\t\tconst list = regionMenu.d.append('div').style('min-width', '140px').style('font-size', '13px')\n\t\tconst addItem = (label: string, action: () => void) => {\n\t\t\tlist\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '6px 12px')\n\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t.style('user-select', 'none')\n\t\t\t\t.text(label)\n\t\t\t\t.on('mouseover', function (this: HTMLDivElement) {\n\t\t\t\t\tthis.style.background = '#f3f4f6'\n\t\t\t\t})\n\t\t\t\t.on('mouseout', function (this: HTMLDivElement) {\n\t\t\t\t\tthis.style.background = ''\n\t\t\t\t})\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tregionMenu.hide()\n\t\t\t\t\taction()\n\t\t\t\t})\n\t\t}\n\t\tconst isHidden = hiddenRegions.has(code)\n\t\tif (isHidden) {\n\t\t\taddItem(`Show ${code}`, () => {\n\t\t\t\thiddenRegions.delete(code)\n\t\t\t\tapplyHiddenRegions()\n\t\t\t})\n\t\t} else {\n\t\t\taddItem(`Hide ${code}`, () => {\n\t\t\t\thiddenRegions.add(code)\n\t\t\t\tapplyHiddenRegions()\n\t\t\t})\n\t\t}\n\t\taddItem(`Show only ${code}`, () => {\n\t\t\thiddenRegions.clear()\n\t\t\tfor (const r of allRegionCodes) if (r !== code) hiddenRegions.add(r)\n\t\t\t// also hide dots whose samples have no brain-region annotation\n\t\t\thiddenRegions.add(NO_REGION)\n\t\t\tapplyHiddenRegions()\n\t\t})\n\t\tif (hiddenRegions.size) {\n\t\t\taddItem('Show all', () => {\n\t\t\t\thiddenRegions.clear()\n\t\t\t\tapplyHiddenRegions()\n\t\t\t})\n\t\t}\n\t\tregionMenu.show(event.clientX, event.clientY)\n\t}\n\n\tconst redraw = async () => {\n\t\tif (!panel) panel = holder.append('div').style('margin-bottom', '14px')\n\t\tpanel.selectAll('*').remove()\n\t\tconst { counts, totalSamples, unmappedCount } = countFromDots(visibleDots)\n\t\tawait drawBrainRegionSamples(panel, {\n\t\t\tregions,\n\t\t\tcounts,\n\t\t\ttotalSamples,\n\t\t\tunmappedCount,\n\t\t\ttemplateUrl: brConfig.templateUrl,\n\t\t\tsvgUrl: brConfig.svgUrl,\n\t\t\ttip: self.dom.tip,\n\t\t\tonRegionClick: openRegionMenu,\n\t\t\t// A region with no visible-dot samples has count 0, which is exactly when it\n\t\t\t// should be dimmed \u2014 so no separate \"visible regions\" set is needed.\n\t\t\tisRegionDimmed: (code: string) => hiddenRegions.has(code) || (counts[code] ?? 0) === 0\n\t\t})\n\t}\n\n\t// Fires once immediately with the initial visible dots, then on every change.\n\tvolcanoApi.onVisibilityChange(({ dots }) => {\n\t\tvisibleDots = dots\n\t\tredraw()\n\t})\n}\n\nfunction renderCohortVolcano(holder: any, data: any, self: ProteinView) {\n\tconst dots: any[] = []\n\t// Global sample-id \u2192 region-code map (deduped, sent once by the proteome route).\n\tconst sampleRegionById: { [sid: string]: string } = data?.sampleRegions || {}\n\n\tfor (const cohortData of data?.cohorts || []) {\n\t\tconst log2fc = getLog2Ratio(cohortData.foldChange)\n\t\tconst pValue = Number(cohortData.pValue)\n\t\tconst testedN = Number(cohortData.testedN)\n\t\tconst controlN = Number(cohortData.controlN)\n\t\tif (log2fc === null || !Number.isFinite(pValue) || pValue <= 0) continue\n\t\tdots.push({\n\t\t\torganismName: cohortData.organism,\n\t\t\tdisease: cohortData.disease,\n\t\t\tassayName: cohortData.assayName,\n\t\t\tcohortName: cohortData.cohortName,\n\t\t\tPTMType: cohortData.PTMType,\n\t\t\tmodSites: cohortData.modSites,\n\t\t\tproteinAccession: cohortData.proteinAccession,\n\t\t\tuniqueIdentifier: cohortData.uniqueIdentifier,\n\t\t\tlog2fc,\n\t\t\tpValue,\n\t\t\tscore: -Math.log10(Math.max(pValue, 1e-300)),\n\t\t\ttestedN: Number.isFinite(testedN) ? testedN : 0,\n\t\t\tcontrolN: Number.isFinite(controlN) ? controlN : 0,\n\t\t\t// per-dot sample identity (case + control); each sample's region comes from the\n\t\t\t// response-level sampleRegions map, used to count brain-region samples that\n\t\t\t// exactly match the visible dots.\n\t\t\tsampleIds: Array.isArray(cohortData.sampleIds) ? cohortData.sampleIds : []\n\t\t})\n\t}\n\n\tconst panel = holder.append('div').style('margin-bottom', '14px')\n\tconst header = panel\n\t\t.append('div')\n\t\t.style('display', 'flex')\n\t\t.style('align-items', 'center')\n\t\t.style('gap', '6px')\n\t\t.style('margin-bottom', '6px')\n\n\tconst downloadBtn = header.append('div').style('display', 'inline-block')\n\n\theader.append('div').style('font-weight', 600).text('Sample Set Volcano')\n\n\tif (!dots.length) {\n\t\tdownloadBtn.style('display', 'none')\n\t\tpanel\n\t\t\t.append('div')\n\t\t\t.style('font-size', '.85em')\n\t\t\t.style('color', '#666')\n\t\t\t.text('No cohorts with valid fold-change and p-value to plot.')\n\t\treturn { setExternallyHiddenCohorts() {}, onVisibilityChange() {} }\n\t}\n\n\tconst width = 500\n\tconst height = 480\n\tconst margin = { top: 20, right: 30, bottom: 60, left: 70 }\n\tconst innerW = width - margin.left - margin.right\n\tconst innerH = height - margin.top - margin.bottom\n\n\tlet minX = Number.POSITIVE_INFINITY\n\tlet maxX = Number.NEGATIVE_INFINITY\n\tlet maxY = 0\n\tlet maxTestedN = 0\n\tlet minTestedN = Number.POSITIVE_INFINITY\n\tfor (const p of dots) {\n\t\tminX = Math.min(minX, p.log2fc)\n\t\tmaxX = Math.max(maxX, p.log2fc)\n\t\tmaxY = Math.max(maxY, p.score)\n\t\tmaxTestedN = Math.max(maxTestedN, p.testedN)\n\t\tif (p.testedN > 0) minTestedN = Math.min(minTestedN, p.testedN)\n\t}\n\n\tif (maxY < 1) maxY = 1\n\tif (!Number.isFinite(minTestedN)) minTestedN = 1\n\n\tconst xSpan = Math.max(0.05, maxX - minX)\n\tconst xPad = Math.max(0.01, xSpan * 0.1)\n\tconst xMin = Math.min(0, minX - xPad)\n\tconst xMax = Math.max(0, maxX + xPad)\n\tconst yMax = maxY * 1.15\n\n\tconst xScale = scaleLinear().domain([xMin, xMax]).range([0, innerW])\n\tconst yScale = scaleLinear().domain([0, yMax]).range([innerH, 0])\n\tconst radiusRange: [number, number] = [4, 12]\n\tconst radiusScale = scaleLinear()\n\t\t.domain([minTestedN, Math.max(minTestedN + 1, maxTestedN)])\n\t\t.range(radiusRange)\n\tlet scaleDotSize = true\n\tconst getDotRadius = (d: any) =>\n\t\tscaleDotSize ? radiusScale(Math.max(minTestedN, d.testedN || minTestedN)) : (radiusRange[0] + radiusRange[1]) / 2\n\n\tconst organismNames = [...new Set(dots.map((d: any) => d.organismName).filter(Boolean))].sort() as string[]\n\tconst assayNames = [...new Set(dots.map((d: any) => d.assayName))].sort() as string[]\n\tconst cohortNames = [...new Set(dots.map((d: any) => d.cohortName))].sort() as string[]\n\tconst proteinAccessions = [...new Set(dots.map((d: any) => d.proteinAccession))].sort() as string[]\n\n\t// Create color scales for each grouping category\n\tconst organismColorScale = getColors(organismNames.length).domain(organismNames)\n\tconst assayColorScale = getColors(assayNames.length).domain(assayNames)\n\tconst cohortColorScale = getColors(cohortNames.length).domain(cohortNames)\n\tconst proteinColorScale = getColors(proteinAccessions.length).domain(proteinAccessions)\n\n\t// Store colors in maps\n\tconst organismColors = new Map<string, string>(\n\t\torganismNames.map(name => [name, rgb(organismColorScale(name)).formatHex()])\n\t)\n\tconst assayColors = new Map<string, string>(assayNames.map(name => [name, rgb(assayColorScale(name)).formatHex()]))\n\tconst cohortColors = new Map<string, string>(cohortNames.map(name => [name, rgb(cohortColorScale(name)).formatHex()]))\n\tconst proteinColors = new Map<string, string>(\n\t\tproteinAccessions.map(acc => [acc, rgb(proteinColorScale(acc)).formatHex()])\n\t)\n\n\t// Prioritize filled shapes first, then empty shapes\n\tconst prioritizedShapesArray = (() => {\n\t\tconst entries = Object.entries(shapes)\n\t\tconst sorted = [\n\t\t\t...entries.filter(([, s]) => s.isFilled === true),\n\t\t\t...entries.filter(([, s]) => s.isFilled === false),\n\t\t\t...entries.filter(([, s]) => !('isFilled' in s))\n\t\t]\n\t\treturn sorted.map(([, s]) => s.path)\n\t})()\n\n\tconst makeShapeMap = (items: string[]) =>\n\t\tnew Map<string, number>(items.map((item, i) => [item, i % prioritizedShapesArray.length]))\n\tconst organismShapes = makeShapeMap(organismNames)\n\tconst assayShapes = makeShapeMap(assayNames)\n\tconst cohortShapes = makeShapeMap(cohortNames)\n\tconst proteinShapes = makeShapeMap(proteinAccessions)\n\n\ttype ColorMode = 'organism' | 'assayType' | 'cohort' | 'proteinAccession'\n\ttype ShapeMode = 'organism' | 'assayType' | 'cohort' | 'proteinAccession'\n\n\tlet colorMode: ColorMode = 'assayType'\n\tlet shapeMode: ShapeMode = 'organism'\n\tconst customGroupPrefix = '__custom_group__:'\n\tconst makeCustomGroupKey = (name: string) => `${customGroupPrefix}${name}`\n\tconst isCustomGroupKey = (value: string) => value.startsWith(customGroupPrefix)\n\tconst getCustomGroupNameFromKey = (value: string) => value.slice(customGroupPrefix.length)\n\tconst customShapeGroupPrefix = '__custom_shape_group__:'\n\tconst makeCustomShapeGroupKey = (name: string) => `${customShapeGroupPrefix}${name}`\n\tconst isCustomShapeGroupKey = (value: string) => value.startsWith(customShapeGroupPrefix)\n\tconst getCustomShapeGroupNameFromKey = (value: string) => value.slice(customShapeGroupPrefix.length)\n\tconst customColorDomain = Array.from({ length: 64 }, (_, i) => `custom-${i}`)\n\tconst customColorScale = getColors(customColorDomain.length).domain(customColorDomain)\n\tconst colorModesWithGroups: ColorMode[] = ['organism', 'assayType', 'cohort', 'proteinAccession']\n\tconst shapeModesWithGroups: ShapeMode[] = ['organism', 'assayType', 'cohort', 'proteinAccession']\n\tconst createModeMap = <T>(factory: () => T) => ({\n\t\torganism: factory(),\n\t\tassayType: factory(),\n\t\tcohort: factory(),\n\t\tproteinAccession: factory()\n\t})\n\tconst customGroupsByMode = createModeMap(() => new Map<string, Set<string>>())\n\tconst customGroupColorsByMode = createModeMap(() => new Map<string, string>())\n\tconst customShapeGroupsByMode = createModeMap(() => new Map<string, Set<string>>())\n\tconst customShapeIndicesByMode = createModeMap(() => new Map<string, number>())\n\tconst checkedItemsByMode = createModeMap(() => new Set<string>())\n\tconst checkedShapeItemsByMode = createModeMap(() => new Set<string>())\n\tconst groupingModeActive = new Set<ColorMode>()\n\tconst shapeGroupingModeActive = new Set<ShapeMode>()\n\tlet customColorSeed = 0\n\n\tconst getBaseColorValue = (d: any, mode: ColorMode) => {\n\t\tswitch (mode) {\n\t\t\tcase 'organism':\n\t\t\t\treturn d.organismName\n\t\t\tcase 'assayType':\n\t\t\t\treturn d.assayName\n\t\t\tcase 'cohort':\n\t\t\t\treturn d.cohortName\n\t\t\tcase 'proteinAccession':\n\t\t\t\treturn d.proteinAccession\n\t\t\tdefault:\n\t\t\t\treturn ''\n\t\t}\n\t}\n\tconst getCustomGroupOfValue = (mode: ColorMode, value: string) => {\n\t\tfor (const [group, members] of customGroupsByMode[mode]) {\n\t\t\tif (members.has(value)) return group\n\t\t}\n\t\treturn null\n\t}\n\tconst getCustomGroupOfDot = (d: any, mode: ColorMode) => {\n\t\treturn getCustomGroupOfValue(mode, getBaseColorValue(d, mode))\n\t}\n\tconst getCustomShapeGroupOfValue = (mode: ShapeMode, value: string) => {\n\t\tfor (const [group, members] of customShapeGroupsByMode[mode]) {\n\t\t\tif (members.has(value)) return group\n\t\t}\n\t\treturn null\n\t}\n\tconst getCustomShapeGroupOfDot = (d: any, mode: ShapeMode) => {\n\t\treturn getCustomShapeGroupOfValue(mode, getBaseColorValue(d, mode))\n\t}\n\tconst getNextCustomColor = () => {\n\t\tconst color = rgb(customColorScale(customColorDomain[customColorSeed % customColorDomain.length])).formatHex()\n\t\tcustomColorSeed++\n\t\treturn color\n\t}\n\tconst addOrUpdateCustomGroup = (mode: ColorMode, name: string, baseValues: string[]) => {\n\t\tif (!name || !baseValues.length) return\n\t\tfor (const members of customGroupsByMode[mode].values()) {\n\t\t\tfor (const val of baseValues) members.delete(val)\n\t\t}\n\t\tconst existing = customGroupsByMode[mode].get(name) || new Set<string>()\n\t\tfor (const val of baseValues) existing.add(val)\n\t\tcustomGroupsByMode[mode].set(name, existing)\n\t\tif (!customGroupColorsByMode[mode].has(name)) customGroupColorsByMode[mode].set(name, getNextCustomColor())\n\t}\n\tconst removeCustomGroup = (mode: ColorMode, name: string) => {\n\t\tcustomGroupsByMode[mode].delete(name)\n\t\tcustomGroupColorsByMode[mode].delete(name)\n\t\thiddenColor[mode].delete(makeCustomGroupKey(name))\n\t}\n\tconst addOrUpdateCustomShapeGroup = (mode: ShapeMode, name: string, baseValues: string[]) => {\n\t\tif (!name || !baseValues.length) return\n\t\tfor (const members of customShapeGroupsByMode[mode].values()) {\n\t\t\tfor (const val of baseValues) members.delete(val)\n\t\t}\n\t\tconst existing = customShapeGroupsByMode[mode].get(name) || new Set<string>()\n\t\tfor (const val of baseValues) existing.add(val)\n\t\tcustomShapeGroupsByMode[mode].set(name, existing)\n\t\tif (!customShapeIndicesByMode[mode].has(name)) {\n\t\t\tconst idx = customShapeIndicesByMode[mode].size % prioritizedShapesArray.length\n\t\t\tcustomShapeIndicesByMode[mode].set(name, idx)\n\t\t}\n\t}\n\tconst removeCustomShapeGroup = (mode: ShapeMode, name: string) => {\n\t\tcustomShapeGroupsByMode[mode].delete(name)\n\t\tcustomShapeIndicesByMode[mode].delete(name)\n\t\thiddenShape[mode].delete(makeCustomShapeGroupKey(name))\n\t}\n\tconst getCustomGroupItems = (mode: ColorMode) => {\n\t\treturn [...customGroupsByMode[mode].keys()].sort().map(name => makeCustomGroupKey(name))\n\t}\n\tconst getCustomShapeGroupItems = (mode: ShapeMode) => {\n\t\treturn [...customShapeGroupsByMode[mode].keys()].sort().map(name => makeCustomShapeGroupKey(name))\n\t}\n\tconst getLegendItemSampleCount = (mode: ColorMode | ShapeMode, item: string, dotsToCount: any[] = dots) => {\n\t\tif (isCustomGroupKey(item)) {\n\t\t\tconst groupName = getCustomGroupNameFromKey(item)\n\t\t\treturn dotsToCount.filter(\n\t\t\t\td => getCustomGroupOfValue(mode as ColorMode, getBaseColorValue(d, mode as ColorMode)) === groupName\n\t\t\t).length\n\t\t}\n\n\t\tif (isCustomShapeGroupKey(item)) {\n\t\t\tconst groupName = getCustomShapeGroupNameFromKey(item)\n\t\t\treturn dotsToCount.filter(\n\t\t\t\td => getCustomShapeGroupOfValue(mode as ShapeMode, getBaseColorValue(d, mode as ColorMode)) === groupName\n\t\t\t).length\n\t\t}\n\n\t\treturn dotsToCount.filter(d => getBaseColorValue(d, mode as ColorMode) === item).length\n\t}\n\tconst getColor = (d: any) => {\n\t\tconst customGroup = getCustomGroupOfDot(d, colorMode)\n\t\tswitch (colorMode) {\n\t\t\tcase 'organism':\n\t\t\t\tif (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? '#888'\n\t\t\t\treturn organismColors.get(d.organismName) ?? '#888'\n\t\t\tcase 'assayType':\n\t\t\t\tif (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? '#888'\n\t\t\t\treturn assayColors.get(d.assayName) ?? '#888'\n\t\t\tcase 'cohort':\n\t\t\t\tif (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? '#888'\n\t\t\t\treturn cohortColors.get(d.cohortName) ?? '#888'\n\t\t\tcase 'proteinAccession':\n\t\t\t\tif (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? '#888'\n\t\t\t\treturn proteinColors.get(d.proteinAccession) ?? '#888'\n\t\t\tdefault:\n\t\t\t\treturn '#888'\n\t\t}\n\t}\n\tconst getShapeIndex = (d: any) => {\n\t\tconst customShapeGroup = getCustomShapeGroupOfDot(d, shapeMode)\n\t\tif (customShapeGroup) {\n\t\t\treturn customShapeIndicesByMode[shapeMode].get(customShapeGroup) ?? 0\n\t\t}\n\t\tswitch (shapeMode) {\n\t\t\tcase 'organism':\n\t\t\t\treturn organismShapes.get(d.organismName) ?? 0\n\t\t\tcase 'assayType':\n\t\t\t\treturn assayShapes.get(d.assayName) ?? 0\n\t\t\tcase 'cohort':\n\t\t\t\treturn cohortShapes.get(d.cohortName) ?? 0\n\t\t\tcase 'proteinAccession':\n\t\t\t\treturn proteinShapes.get(d.proteinAccession) ?? 0\n\t\t\tdefault:\n\t\t\t\treturn 0\n\t\t}\n\t}\n\tconst getShapePath = (d: any) => {\n\t\tconst index = getShapeIndex(d) % prioritizedShapesArray.length\n\t\treturn prioritizedShapesArray[index]\n\t}\n\tconst getShapeTransform = (d: any, sizeScale = 1) => {\n\t\tconst r = getDotRadius(d) * sizeScale\n\t\tconst scale = r / 8\n\t\tconst x = xScale(d.log2fc) - 8 * scale\n\t\tconst y = yScale(d.score) - 8 * scale\n\t\treturn `translate(${x},${y}) scale(${scale})`\n\t}\n\tconst colorGroupingModes: Array<{ key: ColorMode; label: string }> = [\n\t\t{ key: 'organism', label: 'Organism' },\n\t\t{ key: 'assayType', label: 'Assay' },\n\t\t{ key: 'cohort', label: 'Sample Set' },\n\t\t{ key: 'proteinAccession', label: 'Isoform' }\n\t]\n\tconst shapeGroupingModes: Array<{ key: ShapeMode; label: string }> = [\n\t\t{ key: 'organism', label: 'Organism' },\n\t\t{ key: 'assayType', label: 'Assay' },\n\t\t{ key: 'cohort', label: 'Sample Set' },\n\t\t{ key: 'proteinAccession', label: 'Isoform' }\n\t]\n\tconst makeHiddenState = () => ({\n\t\torganism: new Set<string>(),\n\t\tassayType: new Set<string>(),\n\t\tcohort: new Set<string>(),\n\t\tproteinAccession: new Set<string>()\n\t})\n\tconst hiddenColor = makeHiddenState()\n\tconst hiddenShape = makeHiddenState()\n\t// Cohorts hidden by an external driver (the brain plot). Kept separate from\n\t// hiddenColor so manual hide/show in the legend doesn't fight with it.\n\tlet externalHiddenCohorts: Set<string> = new Set()\n\tconst visibilityChangeListeners: ((v: { dots: any[] }) => void)[] = []\n\tconst getColorValueByMode = (d: any, mode: ColorMode) => {\n\t\tswitch (mode) {\n\t\t\tcase 'organism':\n\t\t\t\treturn getCustomGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomGroupKey(getCustomGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.organismName\n\t\t\tcase 'assayType':\n\t\t\t\treturn getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode) as string) : d.assayName\n\t\t\tcase 'cohort':\n\t\t\t\treturn getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode) as string) : d.cohortName\n\t\t\tcase 'proteinAccession':\n\t\t\t\treturn getCustomGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomGroupKey(getCustomGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.proteinAccession\n\t\t\tdefault:\n\t\t\t\treturn ''\n\t\t}\n\t}\n\tconst getShapeValueByMode = (d: any, mode: ShapeMode) => {\n\t\tswitch (mode) {\n\t\t\tcase 'organism':\n\t\t\t\treturn getCustomShapeGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.organismName\n\t\t\tcase 'assayType':\n\t\t\t\treturn getCustomShapeGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.assayName\n\t\t\tcase 'cohort':\n\t\t\t\treturn getCustomShapeGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.cohortName\n\t\t\tcase 'proteinAccession':\n\t\t\t\treturn getCustomShapeGroupOfDot(d, mode)\n\t\t\t\t\t? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode) as string)\n\t\t\t\t\t: d.proteinAccession\n\t\t\tdefault:\n\t\t\t\treturn ''\n\t\t}\n\t}\n\tconst isDotHidden = (d: any) => {\n\t\tconst colorValue = getColorValueByMode(d, colorMode)\n\t\tconst shapeValue = getShapeValueByMode(d, shapeMode)\n\t\treturn (\n\t\t\thiddenColor[colorMode].has(colorValue) ||\n\t\t\thiddenShape[shapeMode].has(shapeValue) ||\n\t\t\texternalHiddenCohorts.has(d.cohortName)\n\t\t)\n\t}\n\tconst getDotDistancePx = (d1: any, d2: any) => {\n\t\tconst x = xScale(d1.log2fc) - xScale(d2.log2fc)\n\t\tconst y = yScale(d1.score) - yScale(d2.score)\n\t\treturn Math.sqrt(x * x + y * y)\n\t}\n\tconst getVisibleDots = () => dots.filter(d => !isDotHidden(d))\n\tconst getVisibleTestedNStats = () => {\n\t\tconst visibleDots = getVisibleDots()\n\t\tif (!visibleDots.length) {\n\t\t\treturn { domainMin: 1, domainMax: 2, minLabel: 0, maxLabel: 0 }\n\t\t}\n\n\t\tlet visibleMax = 0\n\t\tlet visibleMin = Number.POSITIVE_INFINITY\n\t\tfor (const d of visibleDots) {\n\t\t\tvisibleMax = Math.max(visibleMax, d.testedN)\n\t\t\tif (d.testedN > 0) visibleMin = Math.min(visibleMin, d.testedN)\n\t\t}\n\n\t\tif (!Number.isFinite(visibleMin)) visibleMin = 1\n\t\tconst domainMax = Math.max(visibleMin + 1, visibleMax)\n\t\treturn { domainMin: visibleMin, domainMax, minLabel: visibleMin, maxLabel: visibleMax || visibleMin }\n\t}\n\tconst updateRadiusScaleForVisibleDots = () => {\n\t\tconst stats = getVisibleTestedNStats()\n\t\tradiusScale.domain([stats.domainMin, stats.domainMax]).range(radiusRange)\n\t\treturn stats\n\t}\n\tconst getClusterDots = (seed: any) => {\n\t\tconst thresholdPx = 5\n\t\treturn dots\n\t\t\t.filter(d => !isDotHidden(d) && getDotDistancePx(d, seed) < thresholdPx)\n\t\t\t.sort((a, b) => getDotDistancePx(a, seed) - getDotDistancePx(b, seed))\n\t}\n\tconst buildClusterTableData = (clusterDots: any[]): { columns: any[]; rows: any[] } => {\n\t\t// Union semantics: PTM dots and non-PTM dots have different attribute\n\t\t// keys (PTM Type, Modified Site, PTM identifier vs Isoform identifier),\n\t\t// so include any column whose underlying field is present on at least\n\t\t// one row in the cluster. Cells for rows that don't have that field\n\t\t// render as blank.\n\t\tconst hasPtm = clusterDots.some(d => d.PTMType)\n\t\tconst hasNonPtm = clusterDots.some(d => !d.PTMType)\n\t\tconst hasModSites = clusterDots.some(d => d.modSites)\n\n\t\tconst columns: any[] = [{ label: 'Organism' }, { label: 'Assay' }, { label: 'Sample Set' }]\n\t\tif (hasPtm) columns.push({ label: 'PTM Type' })\n\t\tif (hasModSites) columns.push({ label: 'Modified Site' })\n\t\tif (hasPtm) columns.push({ label: 'PTM' })\n\t\tif (hasNonPtm) columns.push({ label: 'Isoform' })\n\t\tcolumns.push({ label: 'log\u2082(FC)', sortable: true }, { label: 'p-value', sortable: true })\n\n\t\tconst rows = clusterDots.map(d => {\n\t\t\tconst isPtm = !!d.PTMType\n\t\t\tconst row: any[] = [{ value: d.organismName || '' }, { value: d.assayName || '' }, { value: d.cohortName || '' }]\n\t\t\tif (hasPtm) row.push({ value: isPtm ? d.PTMType || '' : '' })\n\t\t\tif (hasModSites) row.push({ value: d.modSites || '' })\n\t\t\tif (hasPtm) row.push({ value: isPtm ? d.uniqueIdentifier || '' : '' })\n\t\t\tif (hasNonPtm) row.push({ value: !isPtm ? d.uniqueIdentifier || '' : '' })\n\t\t\trow.push({ value: roundValue(d.log2fc, 3) }, { value: d.pValue.toExponential(2) })\n\t\t\treturn row\n\t\t})\n\t\treturn { columns, rows }\n\t}\n\n\tconst updateDots = () => {\n\t\tcohortDots\n\t\t\t.attr('fill', (d: any) => getColor(d))\n\t\t\t.attr('stroke', (d: any) => getColor(d))\n\t\t\t.attr('stroke-width', 1)\n\t\t\t.attr('d', (d: any) => getShapePath(d))\n\t\t\t.attr('transform', (d: any) => getShapeTransform(d))\n\t\t\t.style('opacity', (d: any) => (isDotHidden(d) ? 0 : 1))\n\t\t\t.style('pointer-events', (d: any) => (isDotHidden(d) ? 'none' : 'auto'))\n\t}\n\tconst getShapeMapInUse = () => {\n\t\tswitch (shapeMode) {\n\t\t\tcase 'organism':\n\t\t\t\treturn organismShapes\n\t\t\tcase 'assayType':\n\t\t\t\treturn assayShapes\n\t\t\tcase 'cohort':\n\t\t\t\treturn cohortShapes\n\t\t\tcase 'proteinAccession':\n\t\t\t\treturn proteinShapes\n\t\t\tdefault:\n\t\t\t\treturn assayShapes\n\t\t}\n\t}\n\n\tconst plotAndLegend = panel\n\t\t.append('div')\n\t\t.style('display', 'flex')\n\t\t.style('align-items', 'flex-start')\n\t\t.style('gap', '4px')\n\t\t.style('flex-wrap', 'wrap')\n\n\tconst svg = plotAndLegend\n\t\t.append('svg')\n\t\t.attr('width', width)\n\t\t.attr('height', height)\n\t\t.style('display', 'block')\n\t\t.style('max-width', '100%')\n\t\t.style('height', 'auto')\n\tconst g = svg.append('g').attr('transform', `translate(${margin.left},${margin.top})`)\n\n\tconst xAxis = g.append('g').attr('transform', `translate(0,${innerH})`).call(axisBottom(xScale))\n\taxisstyle({ axis: xAxis, color: 'black', showline: true })\n\n\tconst yAxis = g.append('g').call(axisLeft(yScale))\n\taxisstyle({ axis: yAxis, color: 'black', showline: true })\n\n\tconst x0 = xScale(0)\n\tconst pThreshold = -Math.log10(0.05)\n\tconst thresholdY = yScale(Math.min(yMax, pThreshold))\n\n\t// Guide lines\n\tg.append('line')\n\t\t.attr('x1', x0)\n\t\t.attr('x2', x0)\n\t\t.attr('y1', 0)\n\t\t.attr('y2', innerH)\n\t\t.attr('stroke', 'black')\n\t\t.attr('stroke-dasharray', '5 4')\n\t\t.attr('stroke-opacity', 0.4)\n\n\tg.append('line')\n\t\t.attr('x1', 0)\n\t\t.attr('x2', innerW)\n\t\t.attr('y1', thresholdY)\n\t\t.attr('y2', thresholdY)\n\t\t.attr('stroke', 'black')\n\t\t.attr('stroke-dasharray', '5 4')\n\t\t.attr('stroke-opacity', 0.4)\n\n\t// Axis labels\n\tg.append('text')\n\t\t.attr('x', innerW / 2)\n\t\t.attr('y', innerH + 44)\n\t\t.attr('text-anchor', 'middle')\n\t\t.style('font-weight', 600)\n\t\t.text('log2 fold change (disease / control)')\n\n\tg.append('text')\n\t\t.attr('transform', `translate(${-50},${innerH / 2}) rotate(-90)`)\n\t\t.attr('text-anchor', 'middle')\n\t\t.style('font-weight', 600)\n\t\t.text('-log10(p-value)')\n\n\t// Points\n\tconst cohortDots = g\n\t\t.selectAll('path.cohort-dot')\n\t\t.data(dots)\n\t\t.enter()\n\t\t.append('path')\n\t\t.attr('class', 'cohort-dot')\n\t\t.attr('transform', (d: any) => getShapeTransform(d, 0.9))\n\t\t.attr('d', (d: any) => getShapePath(d))\n\t\t.attr('fill', (d: any) => getColor(d))\n\t\t.attr('fill-opacity', 0.5)\n\t\t.attr('stroke', (d: any) => getColor(d))\n\t\t.attr('stroke-width', 1)\n\t\t.attr('vector-effect', 'non-scaling-stroke')\n\n\tcohortDots\n\t\t.transition()\n\t\t.duration(350)\n\t\t.attr('d', (d: any) => getShapePath(d))\n\t\t.attr('transform', (d: any) => getShapeTransform(d, 1))\n\n\t// Hover-ring layer \u2014 visual only, never intercepts mouse events.\n\tconst hoverLayer = g.append('g').attr('class', 'cohort-volcano-hover').style('pointer-events', 'none')\n\n\t// Cover rect \u2014 last child so it sits on top of dots and hover shapes.\n\tconst cover = g\n\t\t.append('rect')\n\t\t.attr('class', 'cohort-volcano-cover')\n\t\t.attr('x', 0)\n\t\t.attr('y', 0)\n\t\t.attr('width', innerW)\n\t\t.attr('height', innerH)\n\t\t.attr('fill', 'transparent')\n\t\t.style('pointer-events', 'all')\n\t\t.style('cursor', 'default')\n\n\tupdateDots()\n\n\tconst renderDotInfoTable = (d: any, container: any) => {\n\t\tconst tbl = table2col({ holder: container.append('table') })\n\t\ttbl.addRow('Organism', d.organismName)\n\t\ttbl.addRow('Disease', d.disease)\n\t\ttbl.addRow('Assay', d.assayName)\n\t\ttbl.addRow('Sample Set', d.cohortName)\n\t\t// Distinct brain regions the dot's samples come from (names when configured).\n\t\tconst dotRegions = [\n\t\t\t...new Set((d.sampleIds || []).map((sid: string) => sampleRegionById[sid]).filter(Boolean))\n\t\t] as string[]\n\t\tif (dotRegions.length) {\n\t\t\tconst regionNames = self.app.vocabApi.termdbConfig?.queries?.proteome?.brainRegions?.regions || {}\n\t\t\ttbl.addRow(\n\t\t\t\t'Brain Region',\n\t\t\t\tdotRegions\n\t\t\t\t\t.sort()\n\t\t\t\t\t.map(c => (regionNames[c] ? `${regionNames[c]} (${c})` : c))\n\t\t\t\t\t.join(', ')\n\t\t\t)\n\t\t}\n\t\ttbl.addRow('Protein Accession', d.proteinAccession)\n\t\tif (d.PTMType) {\n\t\t\ttbl.addRow('PTM Type', d.PTMType)\n\t\t\ttbl.addRow('Modified Site', d.modSites)\n\t\t\ttbl.addRow('PTM', d.uniqueIdentifier)\n\t\t} else {\n\t\t\ttbl.addRow('Isoform', d.uniqueIdentifier)\n\t\t}\n\t\ttbl.addRow('log2 fold change', roundValue(d.log2fc, 3))\n\t\ttbl.addRow('p value', d.pValue.toExponential(2))\n\t\ttbl.addRow('-log10(p)', roundValue(d.score, 3))\n\t\ttbl.addRow('Case samples', d.testedN)\n\t\ttbl.addRow('Control samples', d.controlN)\n\t}\n\n\tconst interactions = new DataPointInteractions<any>({\n\t\tcover,\n\t\thoverLayer,\n\t\thoverTip: self.dom.tip,\n\t\tpoints: dots,\n\t\tgetX: (d: any) => xScale(d.log2fc),\n\t\tgetY: (d: any) => yScale(d.score),\n\t\t// Function form because the size-legend menu mutates radiusRange at runtime;\n\t\t// caching this once would leave the broad-query stale after dots are enlarged.\n\t\thitRadius: () => radiusRange[1] + COHORT_VOLCANO_HIT_RADIUS_PADDING_PX,\n\t\tperDotRadius: (d: any) => getDotRadius(d),\n\t\tperDotBuffer: COHORT_VOLCANO_HIT_BUFFER_PX,\n\t\tisHidden: isDotHidden,\n\t\tgetCluster: (seed: any) => getClusterDots(seed),\n\t\ttoHoverSpec: (d: any) => ({\n\t\t\tpath: getShapePath(d),\n\t\t\ttransform: getShapeTransform(d, COHORT_VOLCANO_HOVER_RING_SIZE_SCALE),\n\t\t\tstroke: 'black',\n\t\t\tstrokeWidth: COHORT_VOLCANO_HOVER_RING_STROKE_PX\n\t\t}),\n\t\tmaxTooltipRows: COHORT_VOLCANO_HOVER_MAX_COHORTS,\n\t\titemNoun: 'cohort',\n\t\trenderSingleHoverTooltip: renderDotInfoTable,\n\t\tbuildMultiHitTableData: buildClusterTableData,\n\t\tgetActions: (d: any) => [\n\t\t\t{\n\t\t\t\tlabel: 'Violin plot',\n\t\t\t\tonClick: () => {\n\t\t\t\t\tlaunchViolinPlot(self, d.organismName, d.assayName, d.cohortName, d.uniqueIdentifier)\n\t\t\t\t}\n\t\t\t}\n\t\t],\n\t\trenderSingleHitInfo: renderDotInfoTable,\n\t\tgetRowKey: (d: any) => d.uniqueIdentifier\n\t})\n\n\tinteractions.attach()\n\n\tconst legend = plotAndLegend\n\t\t.append('div')\n\t\t.style('margin', '0')\n\t\t.style('min-width', '220px')\n\t\t.style('font-size', '.75em')\n\t\t.style('color', '#374151')\n\tfunction renderSizeLegend() {\n\t\tlegendSvg.selectAll('*').remove()\n\t\tconst stats = updateRadiusScaleForVisibleDots()\n\n\t\tnew LegendCircleReference({\n\t\t\tg: legendSvg.append('g').attr('transform', 'translate(12, 8)'),\n\t\t\tinputMax: radiusRange[1],\n\t\t\tinputMin: radiusRange[0],\n\t\t\tmaxLabel: stats.maxLabel,\n\t\t\tmaxRadius: radiusScale(stats.domainMax),\n\t\t\tminLabel: stats.minLabel,\n\t\t\tminRadius: radiusScale(stats.domainMin),\n\t\t\ttitle: '',\n\t\t\tmenu: {\n\t\t\t\tminMaxLabel: 'pixels',\n\t\t\t\tcallback: async (obj: { min: number; max: number }) => {\n\t\t\t\t\tradiusRange[0] = obj.min\n\t\t\t\t\tradiusRange[1] = obj.max\n\t\t\t\t\tradiusScale.range([obj.min, obj.max])\n\t\t\t\t\tupdateDots()\n\t\t\t\t\trenderSizeLegend()\n\t\t\t\t}\n\t\t\t}\n\t\t})\n\t}\n\tconst refreshAfterVisibilityChange = () => {\n\t\tupdateRadiusScaleForVisibleDots()\n\t\tupdateDots()\n\t\trenderColorLegend()\n\t\trenderSizeLegend()\n\t\tif (visibilityChangeListeners.length) {\n\t\t\tconst visibleDots = getVisibleDots()\n\t\t\tfor (const cb of visibilityChangeListeners) cb({ dots: visibleDots })\n\t\t}\n\t}\n\n\tconst termName = self.state.config?.tw?.term?.name || ''\n\tconst svgName = `${termName}.cohort-volcano`\n\tconst downloadVolcanoSvg = () => {\n\t\tconst plotNode = svg.node()\n\t\tconst legendNode = legend.node()\n\t\tif (!plotNode) return\n\n\t\tconst plotWidth = width\n\t\tconst plotHeight = height\n\t\tconst legendRect = legendNode?.getBoundingClientRect()\n\t\tconst legendWidth = Math.max(220, Math.ceil(legendRect?.width || 220))\n\t\tconst legendHeight = Math.max(plotHeight, Math.ceil(legendRect?.height || 0))\n\t\tconst gap = 14\n\n\t\tconst combinedSvg = select(creator('svg').call(document.documentElement) as SVGSVGElement)\n\t\t\t.attr('width', plotWidth + gap + legendWidth)\n\t\t\t.attr('height', legendHeight)\n\n\t\tcombinedSvg.append(() => plotNode.cloneNode(true) as SVGSVGElement)\n\n\t\tcombinedSvg\n\t\t\t.append('foreignObject')\n\t\t\t.attr('x', plotWidth + gap)\n\t\t\t.attr('y', 0)\n\t\t\t.attr('width', legendWidth)\n\t\t\t.attr('height', legendHeight)\n\t\t\t.append(() => {\n\t\t\t\tconst clone = legendNode!.cloneNode(true) as HTMLDivElement\n\t\t\t\tclone.style.margin = '0px'\n\t\t\t\tclone.style.minWidth = '0px'\n\t\t\t\treturn clone\n\t\t\t})\n\n\t\tto_svg(combinedSvg.node()!, svgName, { apply_dom_styles: true })\n\t}\n\tcontrolIcons.download(downloadBtn, { handler: downloadVolcanoSvg, title: 'Download' })\n\n\tconst colorLegendDiv = legend.append('div').style('margin-bottom', '12px')\n\tconst shapeLegendDiv = legend.append('div').style('margin-bottom', '12px')\n\tconst sizeLegendRow = legend\n\t\t.append('div')\n\t\t.style('display', 'flex')\n\t\t.style('flex-direction', 'column')\n\t\t.style('gap', '6px')\n\t\t.style('margin-top', '8px')\n\n\tsizeLegendRow.append('div').style('border-top', '1px solid #e5e7eb').style('margin', '8px 0 8px 0')\n\n\tconst sizeModeRow = sizeLegendRow\n\t\t.append('div')\n\t\t.style('display', 'flex')\n\t\t.style('align-items', 'center')\n\t\t.style('gap', '4px')\n\t\t.style('flex-wrap', 'wrap')\n\n\tconst sizeToggleCheckbox = sizeModeRow\n\t\t.append('input')\n\t\t.attr('type', 'checkbox')\n\t\t.attr('aria-label', 'Scale dot size by case sample size')\n\t\t.property('checked', scaleDotSize)\n\t\t.style('cursor', 'pointer')\n\t\t.style('margin', '0')\n\t\t.on('change', function (this: HTMLInputElement) {\n\t\t\tscaleDotSize = this.checked\n\t\t\tsizeModeText.style('opacity', scaleDotSize ? 1 : 0.4)\n\t\t\tlegendSvg.style('opacity', scaleDotSize ? 1 : 0.4)\n\t\t\tupdateDots()\n\t\t\trenderSizeLegend()\n\t\t})\n\tvoid sizeToggleCheckbox\n\n\tconst sizeModeText = sizeModeRow.append('span').style('display', 'inline-flex').style('gap', '6px')\n\tsizeModeText.append('span').text('Scale by')\n\tsizeModeText\n\t\t.append('span')\n\t\t.text('Case sample size')\n\t\t.style('font-weight', '600')\n\t\t.style('text-decoration', 'underline')\n\t\t.style('color', '#111')\n\tsizeModeText.style('opacity', scaleDotSize ? 1 : 0.4)\n\n\tconst legendSvg = sizeLegendRow.append('svg').attr('width', 190).attr('height', 110).style('display', 'block')\n\tlegendSvg.style('opacity', scaleDotSize ? 1 : 0.4)\n\n\tfunction renderColorLegend() {\n\t\tcolorLegendDiv.selectAll('*').remove()\n\t\tshapeLegendDiv.selectAll('*').remove()\n\n\t\tconst setCreateButtonState = (\n\t\t\tcontainer: any,\n\t\t\tisActive: boolean,\n\t\t\tinputSelector: string,\n\t\t\tbuttonSelector: string,\n\t\t\thasCheckedItems: boolean\n\t\t) => {\n\t\t\tif (!isActive) return\n\t\t\tconst inputNode = container.select(inputSelector).node() as HTMLInputElement | null\n\t\t\tconst createBtn = container.select(buttonSelector)\n\t\t\tif (!inputNode || createBtn.empty()) return\n\t\t\tconst shouldDisable = !inputNode.value.trim() || !hasCheckedItems\n\t\t\tcreateBtn\n\t\t\t\t.property('disabled', shouldDisable)\n\t\t\t\t.style('opacity', shouldDisable ? '0.5' : '1')\n\t\t\t\t.style('cursor', shouldDisable ? 'not-allowed' : 'pointer')\n\t\t}\n\n\t\tconst updateColorCreateButtonState = () => {\n\t\t\tsetCreateButtonState(\n\t\t\t\tcolorLegendDiv,\n\t\t\t\tgroupingModeActive.has(colorMode),\n\t\t\t\t'input[data-role=\"custom-group-name\"]',\n\t\t\t\t'button[data-role=\"create-custom-group-submit\"]',\n\t\t\t\tcheckedItemsByMode[colorMode].size > 0\n\t\t\t)\n\t\t}\n\n\t\tconst updateShapeCreateButtonState = () => {\n\t\t\tsetCreateButtonState(\n\t\t\t\tshapeLegendDiv,\n\t\t\t\tshapeGroupingModeActive.has(shapeMode),\n\t\t\t\t'input[data-role=\"custom-shape-group-name\"]',\n\t\t\t\t'button[data-role=\"create-custom-shape-group-submit\"]',\n\t\t\t\tcheckedShapeItemsByMode[shapeMode].size > 0\n\t\t\t)\n\t\t}\n\n\t\tconst modeRow = colorLegendDiv\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '10px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.style('flex-wrap', 'wrap')\n\n\t\tmodeRow.append('span').text('Color by')\n\n\t\tfor (const { key, label } of colorGroupingModes) {\n\t\t\tmodeRow\n\t\t\t\t.append('span')\n\t\t\t\t.text(label)\n\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t.style('font-weight', key === colorMode ? '600' : '400')\n\t\t\t\t.style('text-decoration', key === colorMode ? 'underline' : 'none')\n\t\t\t\t.style('color', key === colorMode ? '#111' : '#6b7280')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tgroupingModeActive.delete(colorMode)\n\t\t\t\t\tcheckedItemsByMode[colorMode].clear()\n\t\t\t\t\tcolorMode = key\n\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t})\n\t\t}\n\n\t\tconst makeLegendItems = (items: string[], colorMap: Map<string, string>) => {\n\t\t\t// Filter dots to exclude those hidden by shape filtering or by the brain\n\t\t\t// plot's region hide (externalHiddenCohorts), so legend n= reflects both.\n\t\t\tconst dotsVisibleByShape = dots.filter(\n\t\t\t\td => !hiddenShape[shapeMode].has(getShapeValueByMode(d, shapeMode)) && !externalHiddenCohorts.has(d.cohortName)\n\t\t\t)\n\t\t\tconst openColorMenu = (event: any, name: string, swatch: any) => {\n\t\t\t\tconst menu = new Menu({ padding: '0px' })\n\t\t\t\tconst div = menu.d.append('div')\n\t\t\t\tconst hidden = hiddenColor[colorMode].has(name)\n\t\t\t\tconst hiddenCount = hiddenColor[colorMode].size\n\n\t\t\t\tdiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t.text(hidden ? 'Show' : 'Hide')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tif (hidden) hiddenColor[colorMode].delete(name)\n\t\t\t\t\t\telse hiddenColor[colorMode].add(name)\n\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t})\n\n\t\t\t\tdiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t.text('Show only')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\thiddenColor[colorMode].clear()\n\t\t\t\t\t\tfor (const item of items) {\n\t\t\t\t\t\t\tif (item != name) hiddenColor[colorMode].add(item)\n\t\t\t\t\t\t}\n\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t})\n\n\t\t\t\tif (hiddenCount > 1)\n\t\t\t\t\tdiv\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t\t.text('Show all')\n\t\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\t\thiddenColor[colorMode].clear()\n\t\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t\t})\n\n\t\t\t\tconst input: any = div\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_sharp_border')\n\t\t\t\t\t.style('padding', '0px 10px')\n\t\t\t\t\t.text('Color:')\n\t\t\t\t\t.append('input')\n\t\t\t\t\t.attr('type', 'color')\n\t\t\t\t\t.attr('value', colorMap.get(name) ?? '#888')\n\t\t\t\t\t.on('change', () => {\n\t\t\t\t\t\tconst newColor = input.node().value\n\t\t\t\t\t\tif (isCustomGroupKey(name)) {\n\t\t\t\t\t\t\tcustomGroupColorsByMode[colorMode].set(getCustomGroupNameFromKey(name), newColor)\n\t\t\t\t\t\t} else if (!isCustomGroupKey(name)) {\n\t\t\t\t\t\t\tif (colorMode == 'organism') organismColors.set(name, newColor)\n\t\t\t\t\t\t\telse if (colorMode == 'assayType') assayColors.set(name, newColor)\n\t\t\t\t\t\t\telse if (colorMode == 'cohort') cohortColors.set(name, newColor)\n\t\t\t\t\t\t\telse if (colorMode == 'proteinAccession') proteinColors.set(name, newColor)\n\t\t\t\t\t\t}\n\t\t\t\t\t\tcolorMap.set(name, newColor)\n\t\t\t\t\t\tswatch.style('background', newColor)\n\t\t\t\t\t\tupdateDots()\n\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t})\n\n\t\t\t\tif (isCustomGroupKey(name))\n\t\t\t\t\tdiv\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t\t.text('Remove group')\n\t\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\t\tremoveCustomGroup(colorMode, getCustomGroupNameFromKey(name))\n\t\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t\t})\n\t\t\t\tmenu.showunder(event.target)\n\t\t\t}\n\n\t\t\tfor (const name of items) {\n\t\t\t\tconst hidden = hiddenColor[colorMode].has(name)\n\t\t\t\tconst isGroup = isCustomGroupKey(name)\n\t\t\t\tconst displayName = isGroup ? getCustomGroupNameFromKey(name) : name\n\t\t\t\tconst inGroup = !isGroup ? getCustomGroupOfValue(colorMode, name) : null\n\t\t\t\tconst sampleCount = getLegendItemSampleCount(colorMode, name, dotsVisibleByShape)\n\t\t\t\tif (sampleCount === 0) continue\n\t\t\t\tconst row = colorLegendDiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.style('display', 'flex')\n\t\t\t\t\t.style('align-items', 'center')\n\t\t\t\t\t.style('gap', '6px')\n\t\t\t\t\t.style('margin-bottom', '3px')\n\t\t\t\tif (!isGroup && groupingModeActive.has(colorMode)) {\n\t\t\t\t\tconst cb = row.append('input').attr('type', 'checkbox').style('cursor', 'pointer').style('flex-shrink', '0')\n\t\t\t\t\tconst cbNode = cb.node() as HTMLInputElement\n\t\t\t\t\tcbNode.checked = checkedItemsByMode[colorMode].has(name)\n\t\t\t\t\tcb.on('change', () => {\n\t\t\t\t\t\tif (cbNode.checked) checkedItemsByMode[colorMode].add(name)\n\t\t\t\t\t\telse checkedItemsByMode[colorMode].delete(name)\n\t\t\t\t\t\tupdateColorCreateButtonState()\n\t\t\t\t\t})\n\t\t\t\t}\n\t\t\t\tconst swatch = row\n\t\t\t\t\t.append('span')\n\t\t\t\t\t.style('display', 'inline-block')\n\t\t\t\t\t.style('width', '10px')\n\t\t\t\t\t.style('height', '10px')\n\t\t\t\t\t.style('border-radius', '50%')\n\t\t\t\t\t.style('background', colorMap.get(name) ?? '#888')\n\t\t\t\t\t.style('opacity', hidden ? 0.35 : 0.8)\n\t\t\t\t\t.style('flex-shrink', '0')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\tswatch.on('click', (event: any) => openColorMenu(event, name, swatch))\n\t\t\t\trow\n\t\t\t\t\t.append('span')\n\t\t\t\t\t.text(`${displayName}, n=${sampleCount}`)\n\t\t\t\t\t.style('text-decoration', hidden ? 'line-through' : 'none')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t.on('click', (event: any) => openColorMenu(event, name, swatch))\n\t\t\t\tif (isGroup) {\n\t\t\t\t\tconst count = customGroupsByMode[colorMode].get(getCustomGroupNameFromKey(name))?.size || 0\n\t\t\t\t\tconst itemLabel =\n\t\t\t\t\t\tcolorMode === 'organism'\n\t\t\t\t\t\t\t? 'organisms'\n\t\t\t\t\t\t\t: colorMode === 'assayType'\n\t\t\t\t\t\t\t? 'assays'\n\t\t\t\t\t\t\t: colorMode === 'cohort'\n\t\t\t\t\t\t\t? 'sample sets'\n\t\t\t\t\t\t\t: colorMode === 'proteinAccession'\n\t\t\t\t\t\t\t? 'isoforms'\n\t\t\t\t\t\t\t: 'items'\n\t\t\t\t\trow.append('span').style('color', '#6b7280').text(`(${count} ${itemLabel})`)\n\t\t\t\t} else if (inGroup) {\n\t\t\t\t\trow.append('span').style('color', '#6b7280').style('font-style', 'italic').text(`\u2192 ${inGroup}`)\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\tconst buildModeLegendItems = (baseItems: string[], baseColorMap: Map<string, string>) => {\n\t\t\t// Hide base items that have been absorbed into a custom group\n\t\t\tconst visibleBaseItems = baseItems.filter(name => !getCustomGroupOfValue(colorMode, name))\n\t\t\tconst mergedColorMap = new Map<string, string>()\n\t\t\tfor (const name of visibleBaseItems) mergedColorMap.set(name, baseColorMap.get(name) ?? '#888')\n\t\t\tfor (const name of getCustomGroupItems(colorMode)) {\n\t\t\t\tconst rawName = getCustomGroupNameFromKey(name)\n\t\t\t\tmergedColorMap.set(name, customGroupColorsByMode[colorMode].get(rawName) ?? '#888')\n\t\t\t}\n\t\t\treturn { items: [...visibleBaseItems, ...getCustomGroupItems(colorMode)], colorMap: mergedColorMap }\n\t\t}\n\n\t\tconst renderCustomGroupControls = () => {\n\t\t\tif (!colorModesWithGroups.includes(colorMode)) return\n\n\t\t\tif (!groupingModeActive.has(colorMode)) {\n\t\t\t\tconst createBtn = colorLegendDiv\n\t\t\t\t\t.append('button')\n\t\t\t\t\t.attr('type', 'button')\n\t\t\t\t\t.style('font-size', '1em')\n\t\t\t\t\t.style('font-weight', '400')\n\t\t\t\t\t.style('margin-top', '6px')\n\t\t\t\t\t.style('padding', '0')\n\t\t\t\t\t.style('border', 'none')\n\t\t\t\t\t.style('border-radius', '0')\n\t\t\t\t\t.style('background', 'transparent')\n\t\t\t\t\t.style('color', '#6b7280')\n\t\t\t\t\t.style('box-shadow', 'none')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t.style('transition', 'color 120ms ease')\n\t\t\t\t\t.text('+ Create custom group')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tgroupingModeActive.add(colorMode)\n\t\t\t\t\t\trenderColorLegend()\n\t\t\t\t\t})\n\t\t\t\tcreateBtn\n\t\t\t\t\t.on('mouseover', function (this: any) {\n\t\t\t\t\t\tselect(this).style('color', '#111827')\n\t\t\t\t\t})\n\t\t\t\t\t.on('mouseout', function (this: any) {\n\t\t\t\t\t\tselect(this).style('color', '#6b7280')\n\t\t\t\t\t})\n\t\t\t\treturn\n\t\t\t}\n\n\t\t\tcolorLegendDiv\n\t\t\t\t.append('div')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.style('color', '#6b7280')\n\t\t\t\t.style('margin-bottom', '4px')\n\t\t\t\t.text('Check items to include in the new group:')\n\n\t\t\tconst controls = colorLegendDiv\n\t\t\t\t.append('div')\n\t\t\t\t.style('display', 'flex')\n\t\t\t\t.style('gap', '6px')\n\t\t\t\t.style('align-items', 'center')\n\t\t\t\t.style('flex-wrap', 'wrap')\n\t\t\t\t.style('margin-top', '4px')\n\n\t\t\tconst nameInput = controls\n\t\t\t\t.append('input')\n\t\t\t\t.attr('data-role', 'custom-group-name')\n\t\t\t\t.attr('type', 'text')\n\t\t\t\t.attr('placeholder', 'Group name')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 4px')\n\t\t\t\t.style('min-width', '100px')\n\t\t\t\t.on('input', () => updateColorCreateButtonState())\n\n\t\t\tcontrols\n\t\t\t\t.append('button')\n\t\t\t\t.attr('data-role', 'create-custom-group-submit')\n\t\t\t\t.attr('type', 'button')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 6px')\n\t\t\t\t.text('Create')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tconst groupName = ((nameInput.node() as HTMLInputElement)?.value || '').trim()\n\t\t\t\t\tif (!groupName || checkedItemsByMode[colorMode].size < 1) return\n\t\t\t\t\taddOrUpdateCustomGroup(colorMode, groupName, [...checkedItemsByMode[colorMode]])\n\t\t\t\t\tcheckedItemsByMode[colorMode].clear()\n\t\t\t\t\tgroupingModeActive.delete(colorMode)\n\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t})\n\n\t\t\tupdateColorCreateButtonState()\n\n\t\t\tcontrols\n\t\t\t\t.append('button')\n\t\t\t\t.attr('type', 'button')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 6px')\n\t\t\t\t.text('Cancel')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tcheckedItemsByMode[colorMode].clear()\n\t\t\t\t\tgroupingModeActive.delete(colorMode)\n\t\t\t\t\trenderColorLegend()\n\t\t\t\t})\n\t\t}\n\n\t\tif (colorMode === 'organism') {\n\t\t\tconst { items, colorMap } = buildModeLegendItems(organismNames, organismColors)\n\t\t\tmakeLegendItems(items, colorMap)\n\t\t\trenderCustomGroupControls()\n\t\t} else if (colorMode === 'assayType') {\n\t\t\tconst { items, colorMap } = buildModeLegendItems(assayNames, assayColors)\n\t\t\tmakeLegendItems(items, colorMap)\n\t\t\trenderCustomGroupControls()\n\t\t} else if (colorMode === 'cohort') {\n\t\t\tconst { items, colorMap } = buildModeLegendItems(cohortNames, cohortColors)\n\t\t\tmakeLegendItems(items, colorMap)\n\t\t\trenderCustomGroupControls()\n\t\t} else if (colorMode === 'proteinAccession') {\n\t\t\tconst { items, colorMap } = buildModeLegendItems(proteinAccessions, proteinColors)\n\t\t\tmakeLegendItems(items, colorMap)\n\t\t\trenderCustomGroupControls()\n\t\t}\n\n\t\tshapeLegendDiv.append('div').style('border-top', '1px solid #e5e7eb').style('margin', '8px 0 8px 0')\n\n\t\tconst shapeModeRow = shapeLegendDiv\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '10px')\n\t\t\t.style('margin-bottom', '6px')\n\t\t\t.style('flex-wrap', 'wrap')\n\n\t\tshapeModeRow.append('span').text('Shape by')\n\n\t\tfor (const { key, label } of shapeGroupingModes) {\n\t\t\tshapeModeRow\n\t\t\t\t.append('span')\n\t\t\t\t.text(label)\n\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t.style('font-weight', key === shapeMode ? '600' : '400')\n\t\t\t\t.style('text-decoration', key === shapeMode ? 'underline' : 'none')\n\t\t\t\t.style('color', key === shapeMode ? '#111' : '#6b7280')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tshapeGroupingModeActive.delete(shapeMode)\n\t\t\t\t\tcheckedShapeItemsByMode[shapeMode].clear()\n\t\t\t\t\tshapeMode = key\n\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t})\n\t\t}\n\n\t\tconst buildShapeLegendItems = (baseItems: string[]) => {\n\t\t\tconst visibleBaseItems = baseItems.filter(name => !getCustomShapeGroupOfValue(shapeMode, name))\n\t\t\treturn { items: [...visibleBaseItems, ...getCustomShapeGroupItems(shapeMode)] }\n\t\t}\n\n\t\tconst drawShapeLegend = (items: string[], shapeMap: Map<string, number>) => {\n\t\t\t// Filter dots to exclude those hidden by color filtering or by the brain\n\t\t\t// plot's region hide (externalHiddenCohorts), so legend n= reflects both.\n\t\t\tconst dotsVisibleByColor = dots.filter(\n\t\t\t\td => !hiddenColor[colorMode].has(getColorValueByMode(d, colorMode)) && !externalHiddenCohorts.has(d.cohortName)\n\t\t\t)\n\t\t\tconst openShapeMenu = (event: any, name: string) => {\n\t\t\t\tconst menu = new Menu({ padding: '0px' })\n\t\t\t\tconst activeShapeMap = isCustomShapeGroupKey(name) ? customShapeIndicesByMode[shapeMode] : getShapeMapInUse()\n\t\t\t\tconst div = menu.d.append('div')\n\t\t\t\tconst hidden = hiddenShape[shapeMode].has(name)\n\t\t\t\tconst hiddenCount = hiddenShape[shapeMode].size\n\n\t\t\t\tdiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t.text(hidden ? 'Show' : 'Hide')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tif (hidden) hiddenShape[shapeMode].delete(name)\n\t\t\t\t\t\telse hiddenShape[shapeMode].add(name)\n\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t})\n\n\t\t\t\tdiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t.text('Show only')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\thiddenShape[shapeMode].clear()\n\t\t\t\t\t\tfor (const item of items) {\n\t\t\t\t\t\t\tif (item != name) hiddenShape[shapeMode].add(item)\n\t\t\t\t\t\t}\n\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t})\n\n\t\t\t\tif (hiddenCount > 1)\n\t\t\t\t\tdiv\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t\t.text('Show all')\n\t\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\t\thiddenShape[shapeMode].clear()\n\t\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t\t})\n\n\t\t\t\tdiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t.text('Change shape')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tdiv.selectAll('*').remove()\n\t\t\t\t\t\tshapeSelector(\n\t\t\t\t\t\t\tdiv,\n\t\t\t\t\t\t\t(index: number) => {\n\t\t\t\t\t\t\t\tconst shapeKey = isCustomShapeGroupKey(name) ? getCustomShapeGroupNameFromKey(name) : name\n\t\t\t\t\t\t\t\tactiveShapeMap.set(shapeKey, index)\n\t\t\t\t\t\t\t\tupdateDots()\n\t\t\t\t\t\t\t\trenderColorLegend()\n\t\t\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t\t\t},\n\t\t\t\t\t\t\tprioritizedShapesArray\n\t\t\t\t\t\t)\n\t\t\t\t\t})\n\n\t\t\t\tif (isCustomShapeGroupKey(name))\n\t\t\t\t\tdiv\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.attr('class', 'sja_menuoption sja_sharp_border')\n\t\t\t\t\t\t.text('Remove group')\n\t\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\t\tremoveCustomShapeGroup(shapeMode, getCustomShapeGroupNameFromKey(name))\n\t\t\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t\t\t\tmenu.hide()\n\t\t\t\t\t\t})\n\n\t\t\t\tmenu.showunder(event.target)\n\t\t\t}\n\n\t\t\tfor (const name of items) {\n\t\t\t\tconst hidden = hiddenShape[shapeMode].has(name)\n\t\t\t\tconst isGroup = isCustomShapeGroupKey(name)\n\t\t\t\tconst displayName = isGroup ? getCustomShapeGroupNameFromKey(name) : name\n\t\t\t\tconst inGroup = !isGroup ? getCustomShapeGroupOfValue(shapeMode, name) : null\n\t\t\t\tconst sampleCount = getLegendItemSampleCount(shapeMode, name, dotsVisibleByColor)\n\t\t\t\tif (sampleCount === 0) continue\n\t\t\t\tconst row = shapeLegendDiv\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.style('display', 'flex')\n\t\t\t\t\t.style('align-items', 'center')\n\t\t\t\t\t.style('gap', '6px')\n\t\t\t\t\t.style('margin-bottom', '3px')\n\t\t\t\tif (!isGroup && shapeGroupingModeActive.has(shapeMode)) {\n\t\t\t\t\tconst cb = row.append('input').attr('type', 'checkbox').style('cursor', 'pointer').style('flex-shrink', '0')\n\t\t\t\t\tconst cbNode = cb.node() as HTMLInputElement\n\t\t\t\t\tcbNode.checked = checkedShapeItemsByMode[shapeMode].has(name)\n\t\t\t\t\tcb.on('change', () => {\n\t\t\t\t\t\tif (cbNode.checked) checkedShapeItemsByMode[shapeMode].add(name)\n\t\t\t\t\t\telse checkedShapeItemsByMode[shapeMode].delete(name)\n\t\t\t\t\t\tupdateShapeCreateButtonState()\n\t\t\t\t\t})\n\t\t\t\t}\n\t\t\t\tconst icon = row\n\t\t\t\t\t.append('svg')\n\t\t\t\t\t.attr('width', 16)\n\t\t\t\t\t.attr('height', 16)\n\t\t\t\t\t.style('display', 'inline-block')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\ticon\n\t\t\t\t\t.append('path')\n\t\t\t\t\t.attr('transform', 'scale(0.8)')\n\t\t\t\t\t.attr(\n\t\t\t\t\t\t'd',\n\t\t\t\t\t\tprioritizedShapesArray[\n\t\t\t\t\t\t\t((isGroup\n\t\t\t\t\t\t\t\t? customShapeIndicesByMode[shapeMode].get(getCustomShapeGroupNameFromKey(name))\n\t\t\t\t\t\t\t\t: shapeMap.get(name)) || 0) % prioritizedShapesArray.length\n\t\t\t\t\t\t]\n\t\t\t\t\t)\n\t\t\t\t\t.attr('fill', '#4b5563')\n\t\t\t\t\t.attr('fill-opacity', hidden ? 0.35 : 0.9)\n\t\t\t\ticon.on('click', (event: any) => openShapeMenu(event, name))\n\t\t\t\trow\n\t\t\t\t\t.append('span')\n\t\t\t\t\t.text(`${displayName}, n=${sampleCount}`)\n\t\t\t\t\t.style('text-decoration', hidden ? 'line-through' : 'none')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t.on('click', (event: any) => openShapeMenu(event, name))\n\t\t\t\tif (isGroup) {\n\t\t\t\t\tconst count = customShapeGroupsByMode[shapeMode].get(getCustomShapeGroupNameFromKey(name))?.size || 0\n\t\t\t\t\tconst itemLabel =\n\t\t\t\t\t\tshapeMode === 'organism'\n\t\t\t\t\t\t\t? 'organisms'\n\t\t\t\t\t\t\t: shapeMode === 'assayType'\n\t\t\t\t\t\t\t? 'assays'\n\t\t\t\t\t\t\t: shapeMode === 'cohort'\n\t\t\t\t\t\t\t? 'sample sets'\n\t\t\t\t\t\t\t: shapeMode === 'proteinAccession'\n\t\t\t\t\t\t\t? 'isoforms'\n\t\t\t\t\t\t\t: 'items'\n\t\t\t\t\trow.append('span').style('color', '#6b7280').text(`(${count} ${itemLabel})`)\n\t\t\t\t} else if (inGroup) {\n\t\t\t\t\trow.append('span').style('color', '#6b7280').style('font-style', 'italic').text(`\u2192 ${inGroup}`)\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\tconst renderShapeCustomGroupControls = () => {\n\t\t\tif (!shapeModesWithGroups.includes(shapeMode)) return\n\n\t\t\tif (!shapeGroupingModeActive.has(shapeMode)) {\n\t\t\t\tconst createBtn = shapeLegendDiv\n\t\t\t\t\t.append('button')\n\t\t\t\t\t.attr('type', 'button')\n\t\t\t\t\t.style('font-size', '1em')\n\t\t\t\t\t.style('font-weight', '400')\n\t\t\t\t\t.style('margin-top', '6px')\n\t\t\t\t\t.style('padding', '0')\n\t\t\t\t\t.style('border', 'none')\n\t\t\t\t\t.style('border-radius', '0')\n\t\t\t\t\t.style('background', 'transparent')\n\t\t\t\t\t.style('color', '#6b7280')\n\t\t\t\t\t.style('box-shadow', 'none')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t.style('transition', 'color 120ms ease')\n\t\t\t\t\t.text('+ Create custom group')\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tshapeGroupingModeActive.add(shapeMode)\n\t\t\t\t\t\trenderColorLegend()\n\t\t\t\t\t})\n\t\t\t\tcreateBtn\n\t\t\t\t\t.on('mouseover', function (this: any) {\n\t\t\t\t\t\tselect(this).style('color', '#111827')\n\t\t\t\t\t})\n\t\t\t\t\t.on('mouseout', function (this: any) {\n\t\t\t\t\t\tselect(this).style('color', '#6b7280')\n\t\t\t\t\t})\n\t\t\t\treturn\n\t\t\t}\n\n\t\t\tshapeLegendDiv\n\t\t\t\t.append('div')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.style('color', '#6b7280')\n\t\t\t\t.style('margin-bottom', '4px')\n\t\t\t\t.text('Check items to include in the new group:')\n\n\t\t\tconst controls = shapeLegendDiv\n\t\t\t\t.append('div')\n\t\t\t\t.style('display', 'flex')\n\t\t\t\t.style('gap', '6px')\n\t\t\t\t.style('align-items', 'center')\n\t\t\t\t.style('flex-wrap', 'wrap')\n\t\t\t\t.style('margin-top', '4px')\n\n\t\t\tconst nameInput = controls\n\t\t\t\t.append('input')\n\t\t\t\t.attr('data-role', 'custom-shape-group-name')\n\t\t\t\t.attr('type', 'text')\n\t\t\t\t.attr('placeholder', 'Group name')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 4px')\n\t\t\t\t.style('min-width', '100px')\n\t\t\t\t.on('input', () => updateShapeCreateButtonState())\n\n\t\t\tcontrols\n\t\t\t\t.append('button')\n\t\t\t\t.attr('data-role', 'create-custom-shape-group-submit')\n\t\t\t\t.attr('type', 'button')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 6px')\n\t\t\t\t.text('Create')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tconst groupName = ((nameInput.node() as HTMLInputElement)?.value || '').trim()\n\t\t\t\t\tif (!groupName || checkedShapeItemsByMode[shapeMode].size < 1) return\n\t\t\t\t\taddOrUpdateCustomShapeGroup(shapeMode, groupName, [...checkedShapeItemsByMode[shapeMode]])\n\t\t\t\t\tcheckedShapeItemsByMode[shapeMode].clear()\n\t\t\t\t\tshapeGroupingModeActive.delete(shapeMode)\n\t\t\t\t\trefreshAfterVisibilityChange()\n\t\t\t\t})\n\n\t\t\tupdateShapeCreateButtonState()\n\n\t\t\tcontrols\n\t\t\t\t.append('button')\n\t\t\t\t.attr('type', 'button')\n\t\t\t\t.style('font-size', '12px')\n\t\t\t\t.style('padding', '2px 6px')\n\t\t\t\t.text('Cancel')\n\t\t\t\t.on('click', () => {\n\t\t\t\t\tcheckedShapeItemsByMode[shapeMode].clear()\n\t\t\t\t\tshapeGroupingModeActive.delete(shapeMode)\n\t\t\t\t\trenderColorLegend()\n\t\t\t\t})\n\t\t}\n\n\t\tif (shapeMode === 'organism') {\n\t\t\tconst { items } = buildShapeLegendItems(organismNames)\n\t\t\tdrawShapeLegend(items, organismShapes)\n\t\t\trenderShapeCustomGroupControls()\n\t\t} else if (shapeMode === 'assayType') {\n\t\t\tconst { items } = buildShapeLegendItems(assayNames)\n\t\t\tdrawShapeLegend(items, assayShapes)\n\t\t\trenderShapeCustomGroupControls()\n\t\t} else if (shapeMode === 'cohort') {\n\t\t\tconst { items } = buildShapeLegendItems(cohortNames)\n\t\t\tdrawShapeLegend(items, cohortShapes)\n\t\t\trenderShapeCustomGroupControls()\n\t\t} else if (shapeMode === 'proteinAccession') {\n\t\t\tconst { items } = buildShapeLegendItems(proteinAccessions)\n\t\t\tdrawShapeLegend(items, proteinShapes)\n\t\t\trenderShapeCustomGroupControls()\n\t\t}\n\t}\n\n\tupdateRadiusScaleForVisibleDots()\n\trenderColorLegend()\n\trenderSizeLegend()\n\n\tconst api: VolcanoApi = {\n\t\tsetExternallyHiddenCohorts(cohorts: Set<string>) {\n\t\t\texternalHiddenCohorts = cohorts\n\t\t\trefreshAfterVisibilityChange()\n\t\t},\n\t\tonVisibilityChange(cb) {\n\t\t\tvisibilityChangeListeners.push(cb)\n\t\t\t// Fire once immediately so the subscriber gets the initial state.\n\t\t\tcb({ dots: getVisibleDots() })\n\t\t}\n\t}\n\treturn api\n}\n\nexport type VolcanoApi = {\n\t// Set the list of cohort names to hide externally (e.g. driven by the brain\n\t// plot). Replaces any previously-set external hides.\n\tsetExternallyHiddenCohorts(cohorts: Set<string>): void\n\t// Subscribe to visibility changes. Called once on subscribe with the current\n\t// state, then on every subsequent change. `dots` is the currently-visible dot\n\t// list (each carrying sampleIds) so subscribers can count the exact samples the\n\t// volcano represents (region per sample comes from the response sampleRegions map).\n\tonVisibilityChange(cb: (v: { dots: any[] }) => void): void\n}\n\nfunction launchViolinPlot(\n\tself: ProteinView,\n\torganismName: string,\n\tassayName: string,\n\tcohortName: string,\n\tisoform: string\n) {\n\tconst selectedProtein = self.state.config?.tw?.term\n\tif (!selectedProtein) throw new Error('proteinView: selected protein term is missing')\n\n\tconst action: any = {\n\t\ttype: 'plot_create',\n\t\tconfig: {\n\t\t\tchartType: 'summary'\n\t\t}\n\t}\n\taction.config.assayCohortTitle = `${organismName} ${assayName}: ${cohortName}`\n\taction.config.proteomeDetails = { organism: organismName, assay: assayName, cohort: cohortName }\n\n\tconst termdbConfig = self.app.vocabApi.termdbConfig\n\tconst proteomeOverlayTerm = termdbConfig?.queries?.proteome?.organisms?.[organismName]?.overlayTerm\n\tconst t = structuredClone(selectedProtein)\n\tt.name = `${t.name}: ${isoform}`\n\tt.dataTypeDetails = { organism: organismName, assay: assayName, cohort: cohortName }\n\taction.config.term = { term: t, q: { mode: NumericModes.continuous } }\n\n\tif (proteomeOverlayTerm) {\n\t\taction.config.term2 = { term: structuredClone(proteomeOverlayTerm), q: {} }\n\t}\n\n\tself.app.dispatch(action)\n}\n\nasync function renderPTMLollipop(holder: any, ptmCohorts: any, self: ProteinView, isoform: string, genome: any) {\n\tif (!ptmCohorts?.length) return\n\n\tconst custom_variants: any[] = []\n\tconst mergedMclassOverride: any = {}\n\tconst gm = await getGmForPTM(ptmCohorts[0].geneName, genome.name, isoform)\n\tfor (const ptm of ptmCohorts) {\n\t\t//use default gene model to get coordinates for all PTM sites, which is sufficient for most cases\n\t\t//and avoids the complexity of mapping between different isoforms. TODO:support isoform-specific mapping.\n\t\tif (!gm) continue\n\t\tconst logValue = getLog2Ratio(ptm.foldChange)\n\t\tconst pValue = Number(ptm.pValue)\n\t\tconst testedN = Number(ptm.testedN)\n\t\tconst controlN = Number(ptm.controlN)\n\n\t\tif (ptm.mclassOverride && typeof ptm.mclassOverride == 'object') {\n\t\t\tObject.assign(mergedMclassOverride, ptm.mclassOverride)\n\t\t}\n\n\t\tconst site = parsePTMModSites(ptm.modSites)\n\t\tif (!site) continue\n\t\tconst pos = aa2gmcoord(site, gm)\n\t\tif (!Number.isInteger(pos)) continue\n\t\tconst ptmClass = Object.keys(ptm.mclassOverride || {})[0]\n\t\tcustom_variants.push({\n\t\t\tchr: gm.chr,\n\t\t\tpos,\n\t\t\tmname: ptm.modSites,\n\t\t\tclass: ptmClass,\n\t\t\tdt: 1,\n\t\t\tlogValue,\n\t\t\tpValue,\n\t\t\ttestedN: Number.isFinite(testedN) ? testedN : null,\n\t\t\tcontrolN: Number.isFinite(controlN) ? controlN : null,\n\t\t\torganism: ptm.organism || null,\n\t\t\tassayName: ptm.assayName || null,\n\t\t\tcohortName: ptm.cohortName || null,\n\t\t\tproteinAccession: ptm.proteinAccession || null,\n\t\t\tPTMStr: ptm.uniqueIdentifier || null,\n\t\t\thtmlSections: [\n\t\t\t\t{\n\t\t\t\t\tkey: 'Action',\n\t\t\t\t\tlabel: 'Launch Violin Plot',\n\t\t\t\t\tcallback: () => launchViolinPlot(self, ptm.organism, ptm.assayName, ptm.cohortName, ptm.uniqueIdentifier)\n\t\t\t\t}\n\t\t\t]\n\t\t})\n\t}\n\tif (!custom_variants.length) return\n\n\tconst mclassOverride = {\n\t\tclassName: 'PTM',\n\t\tclasses: mergedMclassOverride\n\t}\n\n\t// apply mclass override to global mclass, which will be used by the mds3 track to display the PTM sites.\n\t// this is necessary because the lollipop plot relies on mclass for variant\n\t// TODO: find a better way (such as defining PTM-specific class keys) to pass mclass override to the track\n\t// without modifying global mclass, which can have unintended side effects on other plots.\n\tfor (const key in mclassOverride.classes) {\n\t\tif (mclass[key]) Object.assign(mclass[key], mclassOverride.classes[key])\n\t}\n\n\t// create mds3 custom track using numeric mode with logValue on y-axis\n\tconst tk = {\n\t\ttype: 'mds3',\n\t\tname: 'PTMs',\n\t\tcustom_variants: custom_variants,\n\t\tskewerModes: [\n\t\t\t{\n\t\t\t\ttype: 'numeric',\n\t\t\t\tbyAttribute: 'logValue',\n\t\t\t\tlabel: 'Log2FC',\n\t\t\t\ttooltipPrintValue: m => {\n\t\t\t\t\tconst p = Number(m.pValue)\n\t\t\t\t\treturn [\n\t\t\t\t\t\t{ k: 'Organism', v: m.organism ?? 'NA' },\n\t\t\t\t\t\t{ k: 'Assay', v: m.assayName ?? 'NA' },\n\t\t\t\t\t\t{ k: 'Sample set', v: m.cohortName ?? 'NA' },\n\t\t\t\t\t\t{ k: 'PTM', v: m.PTMStr ?? 'NA' },\n\t\t\t\t\t\t{ k: 'Log2 fold change', v: Number.isFinite(m.logValue) ? roundValue(m.logValue, 3) : 'NA' },\n\t\t\t\t\t\t{ k: 'P value', v: Number.isFinite(p) && p > 0 ? p.toExponential(2) : 'NA' },\n\t\t\t\t\t\t{ k: 'Case samples', v: Number.isFinite(m.testedN) ? m.testedN : 'NA' },\n\t\t\t\t\t\t{ k: 'Control samples', v: Number.isFinite(m.controlN) ? m.controlN : 'NA' },\n\t\t\t\t\t\t{ k: 'Protein accession', v: m.proteinAccession ?? 'NA' }\n\t\t\t\t\t]\n\t\t\t\t},\n\t\t\t\tinuse: true,\n\t\t\t\taxisheight: 100\n\t\t\t}\n\t\t],\n\t\tmclassOverride\n\t}\n\n\t// launch block in protein mode with custom track\n\tconst arg = {\n\t\tholder: holder.append('div'),\n\t\tgenome,\n\t\tnobox: true,\n\t\ttklst: [tk],\n\t\tmclassOverride,\n\t\tdebugmode: self.app.opts.debug,\n\t\tquery: gm.isoform,\n\t\thide_dsHandles: true\n\t}\n\n\tconst _ = await import('#src/block.init')\n\tawait _.default(arg)\n}\n\n// return the first valid modification site parsed from the modSites string, which is expected to be in the format like \"S10\", or \"S10,T11\"\n// for now return the first valid site for simplicity. TODO: parse and display multiple sites if available.\nfunction parsePTMModSites(modSites: string) {\n\tif (!modSites) return null\n\tconst regex = /([A-Za-z])(\\d+)/g\n\tlet m\n\twhile ((m = regex.exec(modSites)) !== null) {\n\t\tconst position = Number(m[2])\n\t\tif (!Number.isInteger(position) || position < 1) continue\n\t\treturn position\n\t}\n\treturn null\n}\n\nasync function getGmForPTM(geneName: string, genomeName: string, isoform: string) {\n\tif (!geneName) return null\n\tconst d = await dofetch3('genelookup', {\n\t\tbody: {\n\t\t\tdeep: 1,\n\t\t\tgenome: genomeName,\n\t\t\tinput: geneName\n\t\t}\n\t})\n\n\tif (d.error || !Array.isArray(d.gmlst) || !d.gmlst.length) return null\n\n\tconst normalizedIsoform = isoform?.trim().toUpperCase()\n\tconst gm =\n\t\td.gmlst.find((i: any) => i.isoform && normalizedIsoform && i.isoform.toUpperCase() == normalizedIsoform) ||\n\t\td.gmlst.find((i: any) => i.isdefault) ||\n\t\td.gmlst[0]\n\treturn gm\n}\n\nfunction getLog2Ratio(foldChange: number) {\n\tif (!Number.isFinite(foldChange) || foldChange <= 0) return null\n\treturn Math.log2(foldChange)\n}\n\nexport async function getPlotConfig(opts: any) {\n\tconst config = structuredClone(defaultConfig)\n\tif (!opts.tw) throw new Error('proteinView requires opts.tw')\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: 'proteinView',\n\t\t\t\t\ttw: {\n\t\t\t\t\t\tterm: {\n\t\t\t\t\t\t\tgene: geneSearch.geneSymbol,\n\t\t\t\t\t\t\tname: geneSearch.geneSymbol,\n\t\t\t\t\t\t\ttype: TermTypes.PROTEOME_ABUNDANCE\n\t\t\t\t\t\t}\n\t\t\t\t\t}\n\t\t\t\t}\n\t\t\t})\n\t\t}\n\t})\n}\n\nexport const proteinViewInit = getCompInit(ProteinView)\nexport const componentInit = proteinViewInit\n"],
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