@sjcrh/proteinpaint-client 2.216.0 → 2.217.0

package/dist/proteomeCohortCompare-TYYUF5A5.js.map

@@ -0,0 +1,7 @@
+{
+  "version": 3,
+  "sources": ["../plots/proteomeCohortCompare.ts"],
+  "sourcesContent": ["import type { MassState, BasePlotConfig } from '#mass/types/mass'\nimport { getCompInit, copyMerge, type RxComponent } from '#rx'\nimport { PlotBase } from './PlotBase'\nimport { Menu } from '#dom'\nimport { dofetch3 } from '#common/dofetch'\nimport { scaleLinear, axisBottom, axisLeft } from 'd3'\nimport {\n\tmakeTileGrid,\n\tmakeTileCard,\n\trenderPlaceholderTiles,\n\trenderTileError,\n\ttileExpandState\n} from './proteinView.tiles'\n\n/*\nproteomeCohortCompare \u2014 cross-cohort comparison of standardized fold change (log2FC-z).\n\nLaunched from the Studies catalog when \u22652 cohorts are selected. Fetches the aligned z matrix\nfrom termdb/proteomeCohortCompare and renders:\n  - 2 cohorts  \u2192 a concordance scatter tile (z vs z); points colored by shared DAP direction\n  - \u22653 cohorts \u2192 one live tile card per tool (as in the Protein View): a cohort correlation matrix,\n                 a protein \u00D7 cohort clustered heatmap, a shared-vs-specific DAP overlap (an UpSet\n                 per up/down direction, each intersection click-through to its protein list), and\n                 the trajectory below\n  every tile expands in place (click or \u2922) to the full interactive tool\n  - a series   \u2192 an age/progression trajectory: when the selection contains \u22651 ordered series\n                 (cohorts sharing dataset trajectory.series), one panel per k-means cluster showing\n                 the member proteins' relative-abundance trajectories + a thick eigengene trend line\n*/\n\nconst defaultConfig = { chartType: 'proteomeCohortCompare' }\n\ntype CohortRef = { organism: string; assay: string; cohort: string; label?: string }\n\nconst PLOT = 360\nconst MARGIN = { top: 16, right: 12, bottom: 46, left: 50 }\nconst UP = '#b2182b'\nconst DOWN = '#2166ac'\nconst DISCORDANT = '#e08214' // DAP in both cohorts, opposite directions\nconst NEUTRAL = '#cccccc' // not a shared DAP\n/** default DAP cutoffs. A real DAP needs BOTH a fold-change and a significance cutoff\n *  (the DAP file lists every identified protein). papers use |log2FC-z|>2 (human)/2.5 (mouse)\n *  and FDR<0.05; both are user-adjustable. */\nconst Z_THRESH = 2\nconst FDR_THRESH = 0.05\n\ntype ViewKey = 'scatter' | 'default' | 'heatmap' | 'overlap' | 'trajectory'\n\n/** the comparison tools. Each is a live tile card (Protein View style): the card face shows\n *  the tool rendered at a reduced scale with its side panels hidden; expanding the card shows\n *  the full interactive tool in place. `available` gates the tile on the current\n *  selection; an unavailable tool is shown as a greyed placeholder that says what it needs. */\ntype ToolTile = {\n\tkey: ViewKey\n\ttitle: string\n\tsubtitle: string\n\tavailable: (self: ProteomeCohortCompare, data: any) => boolean\n\tunavailableNote: string\n\trender: (self: ProteomeCohortCompare, data: any) => void\n\t/** optional tool-specific controls, rendered unscaled in the tile card (between subtitle and\n\t *  face) and at the top of the expanded view, so they belong to the tool rather than the plot */\n\tcontrols?: (self: ProteomeCohortCompare, holder: any) => void\n}\n\n/** side panels (cutoff controls, legends, gene lists) carry this class so the tile face can hide them */\nconst PANEL_CLASS = 'sjpp-cc-panel'\n/** the card face: inner box the scaled tool is fitted into */\nconst FACE_W = 206\nconst FACE_H = 170\n\n/** the 2-cohort tool */\nconst PAIR_TILES: ToolTile[] = [\n\t{\n\t\tkey: 'scatter',\n\t\ttitle: 'Concordance scatter',\n\t\tsubtitle: 'log2FC-z of one cohort vs the other',\n\t\tavailable: () => true,\n\t\tunavailableNote: '',\n\t\trender: (self, data) => self.renderScatter(data)\n\t}\n]\n\n/** the \u22653-cohort tools */\nconst TOOL_TILES: ToolTile[] = [\n\t{\n\t\tkey: 'default',\n\t\ttitle: 'Correlation matrix',\n\t\tsubtitle: 'Cohort \u00D7 cohort concordance of log2FC-z',\n\t\tavailable: () => true,\n\t\tunavailableNote: '',\n\t\trender: (self, data) => self.renderMatrix(data),\n\t\tcontrols: (self, holder) => self.renderMatrixMetricSelect(holder)\n\t},\n\t{\n\t\tkey: 'heatmap',\n\t\ttitle: 'Protein heatmap',\n\t\tsubtitle: 'Clustered protein \u00D7 cohort log2FC-z',\n\t\tavailable: (_, data) => !!data.heatmap,\n\t\tunavailableNote: 'Heatmap unavailable for this selection',\n\t\trender: (self, data) => self.renderHeatmap(data.heatmap)\n\t},\n\t{\n\t\tkey: 'overlap',\n\t\ttitle: 'UpSet',\n\t\tsubtitle: 'Shared vs cohort-specific DAPs',\n\t\tavailable: (_, data) => !!data.overlap,\n\t\tunavailableNote: 'Overlap unavailable for this selection',\n\t\trender: (self, data) => self.renderOverlap(data.overlap)\n\t},\n\t{\n\t\tkey: 'trajectory',\n\t\ttitle: 'Trajectory',\n\t\tsubtitle: 'Protein clusters over age / progression',\n\t\tavailable: (self, data) => self.trajectorySeriesCount(data.cohorts) > 0 && Array.isArray(data.trajectory),\n\t\tunavailableNote: 'Needs an ordered series (\u22653 timepoints) in the selection',\n\t\trender: (self, data) => self.renderTrajectory(data.trajectory)\n\t}\n]\n\nclass ProteomeCohortCompare extends PlotBase implements RxComponent {\n\tstatic type = 'proteomeCohortCompare'\n\ttype: string\n\tdom!: {\n\t\tholder: any\n\t\tbody: any\n\t\ttip: Menu\n\t\theader?: any\n\t}\n\tcohorts: CohortRef[] = []\n\tmatrixMetric: 'spearman' | 'pearson' = 'spearman'\n\t/** DAP thresholds (scatter coloring + heatmap row selection) */\n\tzThresh = Z_THRESH\n\tfdrThresh = FDR_THRESH\n\t/** max heatmap rows (DAP-union capped by cross-cohort variance) */\n\tmaxRows = 30\n\t/** number of k-means clusters in the trajectory view */\n\tnClusters = 3\n\t/** trajectory drill-down selection: which series/cluster's genes are listed + highlighted */\n\ttrajSelected: { si: number; pi: number } | null = null\n\t/** last fetched response, kept so threshold changes re-render without refetching */\n\tdata: any = null\n\t/** signature of the current cohort selection \u2014 used to reset the trajectory drill-down when it changes */\n\tcohortKey = ''\n\t/** key of the in-place expanded tile, kept so a refetch or redraw reopens it */\n\texpandedTileKey: ViewKey | null = null\n\n\tconstructor(opts: any, api) {\n\t\tsuper(opts, api)\n\t\tthis.type = ProteomeCohortCompare.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('Cohort Comparison')\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='${this.id}' found`\n\t\treturn { config }\n\t}\n\n\tasync main() {\n\t\tconst config: any = this.state.config\n\t\tthis.cohorts = config.cohorts || []\n\t\tif (this.cohorts.length < 2) {\n\t\t\tthis.dom.body.selectAll('*').remove()\n\t\t\tthis.dom.body.append('div').style('color', '#666').text('Select at least two cohorts to compare.')\n\t\t\treturn\n\t\t}\n\t\t// reset the trajectory drill-down when the cohort selection changes (its si/pi would be stale)\n\t\tconst key = this.cohorts.map(c => `${c.organism}|${c.assay}|${c.cohort}`).join(';')\n\t\tif (key !== this.cohortKey) {\n\t\t\tthis.cohortKey = key\n\t\t\tthis.trajSelected = null\n\t\t}\n\t\tawait this.reload()\n\t}\n\n\tcohortLabel(c: CohortRef) {\n\t\treturn c.label || c.cohort\n\t}\n\n\t/** number of ordered series with \u22653 distinct timepoints among the response cohorts \u2014 gates the\n\t *  Trajectory view (matches the server, which needs \u22653 distinct ages to build a trajectory) */\n\ttrajectorySeriesCount(cohortsData: any[]): number {\n\t\tconst bySeries = new Map<string, Set<number>>()\n\t\tfor (const c of cohortsData || []) {\n\t\t\tconst t = c?.trajectory\n\t\t\tif (!t?.series) continue\n\t\t\tlet vals = bySeries.get(t.series)\n\t\t\tif (!vals) bySeries.set(t.series, (vals = new Set()))\n\t\t\tvals.add(t.value)\n\t\t}\n\t\tlet n = 0\n\t\tfor (const vals of bySeries.values()) if (vals.size >= 3) n++\n\t\treturn n\n\t}\n\n\tasync reload() {\n\t\tconst multi = this.cohorts.length > 2\n\t\tconst data = await dofetch3('termdb/proteomeCohortCompare', {\n\t\t\tbody: {\n\t\t\t\tgenome: this.app.opts.state.vocab.genome,\n\t\t\t\tdslabel: this.app.opts.state.vocab.dslabel,\n\t\t\t\tcohorts: this.cohorts,\n\t\t\t\t// \u22653 cohorts: every tool is rendered as a tile, so fetch them all in one request\n\t\t\t\theatmap: multi,\n\t\t\t\toverlap: multi,\n\t\t\t\ttrajectory: multi,\n\t\t\t\tzThresh: this.zThresh,\n\t\t\t\tfdrThresh: this.fdrThresh,\n\t\t\t\tmaxRows: this.maxRows,\n\t\t\t\tnClusters: this.nClusters\n\t\t\t}\n\t\t}).catch(e => {\n\t\t\tthis.dom.body.selectAll('*').remove()\n\t\t\tthrow e\n\t\t})\n\t\t// clear after the fetch (not before) so the page doesn't collapse and jump while\n\t\t// a cutoff change inside an expanded tile refetches\n\t\tthis.dom.body.selectAll('*').remove()\n\t\t// guard: a missing/failed endpoint (e.g. 404) returns no z matrix \u2014 fail clearly, don't crash\n\t\tif (!data || data.error || !Array.isArray(data.z) || typeof data.sharedGeneCount !== 'number') {\n\t\t\tthis.dom.body\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '12px')\n\t\t\t\t.style('color', '#a00')\n\t\t\t\t.text(\n\t\t\t\t\t(data && data.error) ||\n\t\t\t\t\t\t'Cohort comparison is unavailable \u2014 the server may need to be restarted to load the comparison endpoint.'\n\t\t\t\t)\n\t\t\treturn\n\t\t}\n\t\tthis.data = data\n\t\tif (data.sharedGeneCount < 3) {\n\t\t\tthis.dom.body\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '12px')\n\t\t\t\t.style('color', '#a00')\n\t\t\t\t.text('Too few shared proteins to compare.')\n\t\t\treturn\n\t\t}\n\t\tthis.renderToolTiles(data)\n\t}\n\n\ttiles(): ToolTile[] {\n\t\treturn this.cohorts.length > 2 ? TOOL_TILES : PAIR_TILES\n\t}\n\n\t/** run a renderer (which draws into this.dom.body) against another holder */\n\trenderInto(holder: any, draw: () => void) {\n\t\tconst body = this.dom.body\n\t\tthis.dom.body = holder\n\t\ttry {\n\t\t\tdraw()\n\t\t} finally {\n\t\t\tthis.dom.body = body\n\t\t}\n\t}\n\n\t/** one live tile card per tool (same cards as the Protein View study tiles): the face is the\n\t *  tool drawn at full size then scaled to fit, side panels hidden; expanding the card shows the\n\t *  full tool in place. Tools without data render as greyed placeholders after the live ones. */\n\trenderToolTiles(data: any) {\n\t\tconst grid = makeTileGrid(this.dom.body)\n\t\tconst missing: ToolTile[] = []\n\t\tfor (const tile of this.tiles()) {\n\t\t\tif (!tile.available(this, data)) {\n\t\t\t\tmissing.push(tile)\n\t\t\t\tcontinue\n\t\t\t}\n\t\t\tconst body = makeTileCard(grid, {\n\t\t\t\ttitle: tile.title,\n\t\t\t\tsubtitle: tile.subtitle,\n\t\t\t\tuniform: true,\n\t\t\t\texpand: { render: holder => this.renderExpanded(tile, holder, data), ...tileExpandState(this, tile.key) }\n\t\t\t})\n\t\t\tif (tile.controls) {\n\t\t\t\ttile.controls(this, body.append('div').style('margin-top', '2px'))\n\t\t\t}\n\t\t\t// fixed viewport the scaled drawing is fitted into\n\t\t\tconst face = body\n\t\t\t\t.append('div')\n\t\t\t\t.style('width', `${FACE_W}px`)\n\t\t\t\t.style('height', `${FACE_H}px`)\n\t\t\t\t.style('overflow', 'hidden')\n\t\t\t\t.style('margin-top', '4px')\n\t\t\t\t.attr('title', `Expand ${tile.title}`)\n\t\t\tconst inner = face.append('div').style('display', 'inline-block').style('transform-origin', 'top left')\n\t\t\ttry {\n\t\t\t\tthis.renderInto(inner, () => tile.render(this, data))\n\t\t\t\tinner.selectAll(`.${PANEL_CLASS}`).style('display', 'none')\n\t\t\t\t// fit: measure the unscaled drawing and scale it down to the face\n\t\t\t\tconst node = inner.node() as HTMLElement\n\t\t\t\tconst w = node.scrollWidth || node.offsetWidth\n\t\t\t\tconst h = node.scrollHeight || node.offsetHeight\n\t\t\t\tconst k = w && h ? Math.min(1, FACE_W / w, FACE_H / h) : 1\n\t\t\t\tinner.style('transform', `scale(${k})`)\n\t\t\t\t// center the scaled drawing in the face (transform doesn't affect layout, so offset\n\t\t\t\t// by the leftover space around the scaled box) instead of pinning it top-left\n\t\t\t\tinner\n\t\t\t\t\t.style('margin-left', `${Math.max(0, (FACE_W - w * k) / 2)}px`)\n\t\t\t\t\t.style('margin-top', `${Math.max(0, (FACE_H - h * k) / 2)}px`)\n\t\t\t\t// the face is a preview: swallow clicks that would drill down from the mini drawing\n\t\t\t\tinner.style('pointer-events', 'none')\n\t\t\t} catch (err: any) {\n\t\t\t\trenderTileError(face, err, this)\n\t\t\t}\n\t\t}\n\t\trenderPlaceholderTiles(\n\t\t\tgrid,\n\t\t\tmissing.map(t => ({ title: t.title, note: t.unavailableNote }))\n\t\t)\n\t}\n\n\t/** the expanded tile: the full interactive tool with its side panels and controls */\n\trenderExpanded(tile: ToolTile, holder: any, data: any) {\n\t\tif (tile.controls) tile.controls(this, holder.append('div').style('margin-bottom', '8px'))\n\t\ttry {\n\t\t\tthis.renderInto(holder.append('div'), () => tile.render(this, data))\n\t\t} catch (err: any) {\n\t\t\trenderTileError(holder, err, this)\n\t\t}\n\t}\n\n\t/** Spearman/Pearson toggle for the correlation matrix. The response carries both matrices,\n\t *  so switching only redraws the tiles \u2014 no refetch. */\n\trenderMatrixMetricSelect(holder: any) {\n\t\tconst label = holder.append('label').style('font-size', '0.8em').style('color', '#374151')\n\t\tlabel.append('span').style('margin-right', '6px').text('Correlation:')\n\t\tconst sel = label\n\t\t\t.append('select')\n\t\t\t.style('font-size', '1em')\n\t\t\t.on('change', (event: any) => {\n\t\t\t\tthis.matrixMetric = event.target.value\n\t\t\t\tthis.redrawTools()\n\t\t\t})\n\t\tfor (const m of ['spearman', 'pearson']) {\n\t\t\tconst o = sel\n\t\t\t\t.append('option')\n\t\t\t\t.attr('value', m)\n\t\t\t\t.text(m[0].toUpperCase() + m.slice(1))\n\t\t\tif (m === this.matrixMetric) o.property('selected', true)\n\t\t}\n\t}\n\n\t/** re-render the tool tiles (and the expanded one) from the cached response (no refetch) */\n\tredrawTools() {\n\t\tif (!this.data) return\n\t\tthis.dom.body.selectAll('*').remove()\n\t\tthis.renderToolTiles(this.data)\n\t}\n\n\trenderScatter(data: any) {\n\t\tconst [ca, cb] = this.cohorts\n\t\tconst zx: number[] = data.z[0]\n\t\tconst zy: number[] = data.z[1]\n\t\tconst px: number[] = data.fdr[0] // per-cohort FDR for the shared genes\n\t\tconst py: number[] = data.fdr[1]\n\t\tconst genes: string[] = data.genes\n\t\tconst rho: number = data.spearman[0][1]\n\t\tconst r: number = data.pearson[0][1]\n\t\tconst rhoP: number | null = data.spearmanP?.[0]?.[1] ?? null\n\t\tconst rP: number | null = data.pearsonP?.[0]?.[1] ?? null\n\t\tconst fmtP = (p: number | null) =>\n\t\t\tp === null || !Number.isFinite(p) ? '' : `, p = ${p < 1e-4 ? p.toExponential(1) : p.toFixed(4)}`\n\t\tconst n: number = data.sharedGeneCount\n\t\tconst zT = this.zThresh\n\t\tconst fT = this.fdrThresh\n\n\t\t// a protein is a DAP in a cohort only if it clears BOTH the |z| and FDR cutoffs.\n\t\t// classify by shared direction across the two cohorts.\n\t\tconst isDap = (z: number, fdr: number) => Math.abs(z) >= zT && fdr <= fT\n\t\tconst catOf = (i: number): 'up' | 'down' | 'discordant' | 'other' => {\n\t\t\tif (!isDap(zx[i], px[i]) || !isDap(zy[i], py[i])) return 'other'\n\t\t\tconst a = zx[i] > 0,\n\t\t\t\tb = zy[i] > 0\n\t\t\tif (a && b) return 'up'\n\t\t\tif (!a && !b) return 'down'\n\t\t\treturn 'discordant'\n\t\t}\n\t\tconst cats = genes.map((_, i) => catOf(i))\n\t\tconst counts = { up: 0, down: 0, discordant: 0, other: 0 }\n\t\tfor (const c of cats) counts[c]++\n\t\tconst catColor = { up: UP, down: DOWN, discordant: DISCORDANT, other: NEUTRAL }\n\n\t\t// --- plot on the left, info/controls/legend panel on the right ---\n\t\tconst row = this.dom.body\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '18px')\n\t\t\t.style('align-items', 'flex-start')\n\n\t\t// axes on the ACTUAL data extent (no empty margins around the cloud)\n\t\tlet xmin = Infinity,\n\t\t\txmax = -Infinity,\n\t\t\tymin = Infinity,\n\t\t\tymax = -Infinity\n\t\tfor (let i = 0; i < genes.length; i++) {\n\t\t\tif (zx[i] < xmin) xmin = zx[i]\n\t\t\tif (zx[i] > xmax) xmax = zx[i]\n\t\t\tif (zy[i] < ymin) ymin = zy[i]\n\t\t\tif (zy[i] > ymax) ymax = zy[i]\n\t\t}\n\t\tconst padX = (xmax - xmin) * 0.04 || 1\n\t\tconst padY = (ymax - ymin) * 0.04 || 1\n\t\tconst x = scaleLinear()\n\t\t\t.domain([xmin - padX, xmax + padX])\n\t\t\t.range([MARGIN.left, MARGIN.left + PLOT])\n\t\tconst y = scaleLinear()\n\t\t\t.domain([ymin - padY, ymax + padY])\n\t\t\t.range([MARGIN.top + PLOT, MARGIN.top])\n\n\t\tconst svg = row\n\t\t\t.append('svg')\n\t\t\t.attr('width', MARGIN.left + PLOT + MARGIN.right)\n\t\t\t.attr('height', MARGIN.top + PLOT + MARGIN.bottom)\n\n\t\t// zero reference lines (only when 0 is within the plotted range)\n\t\tif (xmin < 0 && xmax > 0)\n\t\t\tsvg\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', x(0))\n\t\t\t\t.attr('y1', MARGIN.top)\n\t\t\t\t.attr('x2', x(0))\n\t\t\t\t.attr('y2', MARGIN.top + PLOT)\n\t\t\t\t.attr('stroke', '#eee')\n\t\tif (ymin < 0 && ymax > 0)\n\t\t\tsvg\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', MARGIN.left)\n\t\t\t\t.attr('y1', y(0))\n\t\t\t\t.attr('x2', MARGIN.left + PLOT)\n\t\t\t\t.attr('y2', y(0))\n\t\t\t\t.attr('stroke', '#eee')\n\n\t\t// points \u2014 draw the grey background cloud first, colored shared movers on top\n\t\tconst pts = svg.append('g')\n\t\tconst drawPoint = (i: number) => {\n\t\t\tconst c = cats[i]\n\t\t\tpts\n\t\t\t\t.append('circle')\n\t\t\t\t.attr('cx', x(zx[i]))\n\t\t\t\t.attr('cy', y(zy[i]))\n\t\t\t\t.attr('r', c === 'other' ? 1.8 : 2.6)\n\t\t\t\t.attr('fill', catColor[c])\n\t\t\t\t.attr('fill-opacity', c === 'other' ? 0.3 : 0.8)\n\t\t\t\t.on('mouseover', (event: any) => {\n\t\t\t\t\tthis.dom.tip.clear().show(event.clientX, event.clientY)\n\t\t\t\t\tthis.dom.tip.d\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.style('padding', '5px 8px')\n\t\t\t\t\t\t.style('font-size', '0.85em')\n\t\t\t\t\t\t.html(\n\t\t\t\t\t\t\t`<b>${genes[i]}</b><br>${this.cohortLabel(ca)}: z=${zx[i].toFixed(2)} (log2FC ${data.fc[0][i].toFixed(\n\t\t\t\t\t\t\t\t2\n\t\t\t\t\t\t\t)}, FDR ${px[i].toExponential(1)})<br>${this.cohortLabel(cb)}: z=${zy[i].toFixed(2)} (log2FC ${data.fc[1][\n\t\t\t\t\t\t\t\ti\n\t\t\t\t\t\t\t].toFixed(2)}, FDR ${py[i].toExponential(1)})`\n\t\t\t\t\t\t)\n\t\t\t\t})\n\t\t\t\t.on('mouseout', () => this.dom.tip.hide())\n\t\t}\n\t\tfor (let i = 0; i < genes.length; i++) if (cats[i] === 'other') drawPoint(i)\n\t\tfor (let i = 0; i < genes.length; i++) if (cats[i] !== 'other') drawPoint(i)\n\n\t\t// axes + titles\n\t\tsvg\n\t\t\t.append('g')\n\t\t\t.attr('transform', `translate(0,${MARGIN.top + PLOT})`)\n\t\t\t.call(axisBottom(x).ticks(5) as any)\n\t\tsvg\n\t\t\t.append('g')\n\t\t\t.attr('transform', `translate(${MARGIN.left},0)`)\n\t\t\t.call(axisLeft(y).ticks(5) as any)\n\t\tsvg\n\t\t\t.append('text')\n\t\t\t.attr('x', MARGIN.left + PLOT / 2)\n\t\t\t.attr('y', MARGIN.top + PLOT + 36)\n\t\t\t.attr('text-anchor', 'middle')\n\t\t\t.style('font-size', '11px')\n\t\t\t.text(`${this.cohortLabel(ca)}  (log2FC-z)`)\n\t\tsvg\n\t\t\t.append('text')\n\t\t\t.attr('transform', `translate(12,${MARGIN.top + PLOT / 2}) rotate(-90)`)\n\t\t\t.attr('text-anchor', 'middle')\n\t\t\t.style('font-size', '11px')\n\t\t\t.text(`${this.cohortLabel(cb)}  (log2FC-z)`)\n\n\t\t// --- right panel: stats, DAP-cutoff controls, legend ---\n\t\tconst panel = row\n\t\t\t.append('div')\n\t\t\t.classed(PANEL_CLASS, true)\n\t\t\t.style('font-size', '0.85em')\n\t\t\t.style('padding-top', '4px')\n\t\t\t.style('min-width', '190px')\n\n\t\tconst statBox = panel.append('div').style('margin-bottom', '12px').style('line-height', '1.6')\n\t\tstatBox\n\t\t\t.append('div')\n\t\t\t.attr('title', 'Number of shared proteins compared')\n\t\t\t.html(`<b>n</b> = ${n.toLocaleString()} shared proteins`)\n\t\tstatBox\n\t\t\t.append('div')\n\t\t\t.attr('title', 'Spearman rank correlation of log2FC-z (robust; no linearity assumption)')\n\t\t\t.html(`<b>\u03C1</b> (Spearman) = ${rho.toFixed(3)}${fmtP(rhoP)}`)\n\t\tstatBox\n\t\t\t.append('div')\n\t\t\t.attr('title', 'Pearson correlation of log2FC-z (linear agreement; the papers\u2019 R)')\n\t\t\t.html(`<b>r</b> (Pearson) = ${r.toFixed(3)}${fmtP(rP)}`)\n\n\t\t// DAP-cutoff controls \u2014 recolor without refetching\n\t\tconst cutoffs = panel.append('div').style('margin-bottom', '12px')\n\t\tcutoffs\n\t\t\t.append('div')\n\t\t\t.style('font-weight', '600')\n\t\t\t.style('margin-bottom', '3px')\n\t\t\t.attr('title', 'A protein is a shared DAP only if it clears BOTH cutoffs in BOTH cohorts')\n\t\t\t.text('DAP cutoffs')\n\t\tconst numInput = (label: string, value: number, step: number, title: string, onSet: (v: number) => void) => {\n\t\t\tconst l = cutoffs.append('div').style('margin-bottom', '2px').attr('title', title)\n\t\t\tl.append('span').style('display', 'inline-block').style('width', '44px').html(label)\n\t\t\tl.append('input')\n\t\t\t\t.attr('type', 'number')\n\t\t\t\t.attr('step', step)\n\t\t\t\t.attr('min', 0)\n\t\t\t\t.property('value', value)\n\t\t\t\t.style('width', '70px')\n\t\t\t\t.on('change', (event: any) => {\n\t\t\t\t\tconst v = Number(event.target.value)\n\t\t\t\t\tif (Number.isFinite(v) && v >= 0) {\n\t\t\t\t\t\tonSet(v)\n\t\t\t\t\t\tthis.redrawTools()\n\t\t\t\t\t}\n\t\t\t\t})\n\t\t}\n\t\tnumInput('|z| \u2265', this.zThresh, 0.5, 'Minimum |log2FC-z| (standardized fold change)', v => (this.zThresh = v))\n\t\tnumInput('FDR \u2264', this.fdrThresh, 0.01, 'Maximum FDR', v => (this.fdrThresh = v))\n\n\t\t// legend\n\t\tconst legend = panel.append('div')\n\t\tlegend.append('div').style('font-weight', '600').style('margin-bottom', '6px').text('Shared regulation')\n\t\tconst legItems: [string, string, number][] = [\n\t\t\t[UP, 'Up in both', counts.up],\n\t\t\t[DOWN, 'Down in both', counts.down],\n\t\t\t[DISCORDANT, 'Opposite (DAP in both)', counts.discordant],\n\t\t\t[NEUTRAL, 'Not a shared DAP', counts.other]\n\t\t]\n\t\tfor (const [col, lab, ct] of legItems) {\n\t\t\tconst item = legend\n\t\t\t\t.append('div')\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('margin-bottom', '3px')\n\t\t\titem\n\t\t\t\t.append('span')\n\t\t\t\t.style('width', '10px')\n\t\t\t\t.style('height', '10px')\n\t\t\t\t.style('border-radius', '50%')\n\t\t\t\t.style('background', col)\n\t\t\t\t.style('display', 'inline-block')\n\t\t\titem.append('span').html(`${lab} <span style=\"color:#999\">(${ct.toLocaleString()})</span>`)\n\t\t}\n\t}\n\n\trenderMatrix(data: any) {\n\t\tconst n = this.cohorts.length\n\t\tconst corr: number[][] = data[this.matrixMetric]\n\t\tconst order = leafOrder(corr)\n\t\tconst labels = order.map(i => this.cohortLabel(this.cohorts[i]))\n\n\t\tconst cell = Math.max(26, Math.min(48, Math.floor(360 / n)))\n\t\t// label gutter sized to the longest label (\u22486.5px/char at 11px) so short names don't\n\t\t// leave a blank strip on the left that throws the tile preview off-center\n\t\tconst maxLabelLen = Math.max(...labels.map(l => l.length))\n\t\tconst labelPad = Math.min(120, Math.max(40, Math.ceil(maxLabelLen * 6.5) + 12))\n\t\tconst svg = this.dom.body\n\t\t\t.append('svg')\n\t\t\t.attr('width', labelPad + n * cell + 60)\n\t\t\t.attr('height', labelPad + n * cell + 20)\n\n\t\tconst cscale = scaleLinear<string>().domain([-1, 0, 1]).range([DOWN, '#f7f7f7', UP]).clamp(true)\n\n\t\tconst g = svg.append('g').attr('transform', `translate(${labelPad},${labelPad})`)\n\t\tfor (let ri = 0; ri < n; ri++) {\n\t\t\tfor (let ci = 0; ci < n; ci++) {\n\t\t\t\tconst v = corr[order[ri]][order[ci]]\n\t\t\t\tg.append('rect')\n\t\t\t\t\t.attr('x', ci * cell)\n\t\t\t\t\t.attr('y', ri * cell)\n\t\t\t\t\t.attr('width', cell - 1)\n\t\t\t\t\t.attr('height', cell - 1)\n\t\t\t\t\t.attr('fill', cscale(v))\n\t\t\t\t\t.style('cursor', ri === ci ? 'default' : 'pointer')\n\t\t\t\t\t.on('mouseover', (event: any) => {\n\t\t\t\t\t\tthis.dom.tip.clear().show(event.clientX, event.clientY)\n\t\t\t\t\t\tthis.dom.tip.d\n\t\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t\t.style('padding', '5px 8px')\n\t\t\t\t\t\t\t.style('font-size', '0.85em')\n\t\t\t\t\t\t\t.html(`${labels[ri]} \u00D7 ${labels[ci]}<br><b>${this.matrixMetric} = ${v.toFixed(3)}</b>`)\n\t\t\t\t\t})\n\t\t\t\t\t.on('mouseout', () => this.dom.tip.hide())\n\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\tif (ri === ci) return\n\t\t\t\t\t\tthis.openPair(this.cohorts[order[ri]], this.cohorts[order[ci]])\n\t\t\t\t\t})\n\t\t\t\tg.append('text')\n\t\t\t\t\t.attr('x', ci * cell + cell / 2)\n\t\t\t\t\t.attr('y', ri * cell + cell / 2)\n\t\t\t\t\t.attr('text-anchor', 'middle')\n\t\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t\t.style('font-size', '10px')\n\t\t\t\t\t.style('fill', Math.abs(v) > 0.6 ? '#fff' : '#333')\n\t\t\t\t\t.style('pointer-events', 'none') // let hover/click fall through to the cell rect below\n\t\t\t\t\t.text(v.toFixed(2))\n\t\t\t}\n\t\t}\n\n\t\t// row labels (left) + column labels (top, rotated)\n\t\tfor (let i = 0; i < n; i++) {\n\t\t\tsvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', labelPad - 6)\n\t\t\t\t.attr('y', labelPad + i * cell + cell / 2)\n\t\t\t\t.attr('text-anchor', 'end')\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.text(labels[i])\n\t\t\tsvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('transform', `translate(${labelPad + i * cell + cell / 2},${labelPad - 6}) rotate(-45)`)\n\t\t\t\t.attr('text-anchor', 'start')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.text(labels[i])\n\t\t}\n\n\t\tthis.dom.body\n\t\t\t.append('div')\n\t\t\t.classed(PANEL_CLASS, true)\n\t\t\t.style('font-size', '0.8em')\n\t\t\t.style('color', '#777')\n\t\t\t.style('margin-top', '6px')\n\t\t\t.text('Rows/cols ordered by hierarchical clustering. Click a cell to open the pairwise scatter.')\n\t}\n\n\t/** open a fresh 2-cohort comparison for the clicked matrix pair */\n\topenPair(a: CohortRef, b: CohortRef) {\n\t\tthis.app.dispatch({\n\t\t\ttype: 'plot_create',\n\t\t\tconfig: { chartType: 'proteomeCohortCompare', cohorts: [a, b] }\n\t\t})\n\t}\n\n\t/** protein \u00D7 cohort log2FC-z heatmap, clustered on both axes (via server hclust.R) */\n\trenderHeatmap(hm: any) {\n\t\tif (!hm) {\n\t\t\tthis.dom.body.append('div').style('padding', '12px').style('color', '#a00').text('Heatmap unavailable.')\n\t\t\treturn\n\t\t}\n\n\t\t// layout: heatmap on the left, controls + legend + count on the right, bottom-aligned to the heatmap\n\t\tconst wrap = this.dom.body\n\t\t\t.append('div')\n\t\t\t.style('display', 'flex')\n\t\t\t.style('gap', '18px')\n\t\t\t.style('align-items', 'flex-end')\n\t\tconst left = wrap.append('div')\n\t\tconst panel = wrap.append('div').classed(PANEL_CLASS, true).style('font-size', '0.85em').style('min-width', '160px')\n\n\t\t// DAP-cutoff + row-cap controls \u2014 changing any recomputes rows/clustering on the server\n\t\tpanel.append('div').style('font-weight', '600').style('margin-bottom', '3px').text('DAP cutoffs')\n\t\tconst numInput = (label: string, value: number, step: number, title: string, onSet: (v: number) => void) => {\n\t\t\tconst l = panel.append('div').style('margin-bottom', '3px').attr('title', title)\n\t\t\tl.append('span').style('display', 'inline-block').style('width', '58px').html(label)\n\t\t\tl.append('input')\n\t\t\t\t.attr('type', 'number')\n\t\t\t\t.attr('step', step)\n\t\t\t\t.attr('min', 0)\n\t\t\t\t.property('value', value)\n\t\t\t\t.style('width', '64px')\n\t\t\t\t.on('change', (e: any) => {\n\t\t\t\t\tconst v = Number(e.target.value)\n\t\t\t\t\tif (Number.isFinite(v) && v >= 0) {\n\t\t\t\t\t\tonSet(v)\n\t\t\t\t\t\tthis.reload()\n\t\t\t\t\t}\n\t\t\t\t})\n\t\t}\n\t\tnumInput('|z| \u2265', this.zThresh, 0.5, 'DAP fold-change cutoff', v => (this.zThresh = v))\n\t\tnumInput('FDR \u2264', this.fdrThresh, 0.01, 'DAP significance cutoff (FDR)', v => (this.fdrThresh = v))\n\t\tnumInput(\n\t\t\t'max rows',\n\t\t\tthis.maxRows,\n\t\t\t25,\n\t\t\t'Cap on proteins shown (top by variance of z across cohorts)',\n\t\t\tv => (this.maxRows = Math.round(v))\n\t\t)\n\t\t// color legend goes here, directly under the DAP cutoffs (filled in once `cap` is known)\n\t\tconst legendHolder = panel.append('div').style('margin-top', '12px')\n\t\tconst countTxt =\n\t\t\thm.shown < hm.totalDap ? `${hm.shown} of ${hm.totalDap} DAP-union proteins` : `${hm.shown} DAP-union proteins`\n\t\tpanel.append('div').style('margin-top', '12px').style('color', '#777').text(countTxt)\n\n\t\tif (!hm.rowNames.length) {\n\t\t\tleft\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '12px')\n\t\t\t\t.style('color', '#a00')\n\t\t\t\t.text('No DAP proteins at these cutoffs \u2014 loosen |z| or FDR.')\n\t\t\treturn\n\t\t}\n\n\t\tconst rows: string[] = hm.rowNames\n\t\tconst cols: string[] = hm.colLabels\n\t\tconst Z: number[][] = hm.z\n\t\tconst cellW = 45\n\t\t// cap the gene-rows grid at MAX_GRID_H px tall; shrink cell height when there are many genes,\n\t\t// and drop the gene names once cells get too short to fit readable text (hover still shows them)\n\t\tconst MAX_GRID_H = 600\n\t\tconst cellH = Math.min(18, MAX_GRID_H / rows.length)\n\t\tconst showRowNames = cellH >= 8\n\t\tconst rowDendW = hm.rowDendrogram ? 90 : 0\n\t\tconst colDendH = hm.colDendrogram ? 70 : 0\n\t\tconst maxLabelLen = Math.max(1, ...cols.map(c => c.length))\n\t\t// size the vertical-label band to the longest name + a gap so labels never touch the top dendrogram\n\t\tconst colLabelH = Math.min(220, Math.max(70, Math.round(maxLabelLen * 7) + 12))\n\t\tconst rowLabelW = showRowNames ? 140 : 8\n\t\tconst legendW = 12 // just a little right padding now that the legend lives in the side panel\n\t\tconst gridW = cols.length * cellW\n\t\tconst gridH = rows.length * cellH\n\t\tconst gridX = rowDendW\n\t\tconst gridY = colDendH + colLabelH\n\n\t\tconst svg = left\n\t\t\t.append('svg')\n\t\t\t.attr('width', gridX + gridW + rowLabelW + legendW)\n\t\t\t.attr('height', gridY + gridH + 12)\n\t\t\t.attr('font-family', 'sans-serif')\n\n\t\tlet cap = 1\n\t\tfor (const row of Z) for (const v of row) cap = Math.max(cap, Math.abs(v))\n\t\tconst color = scaleLinear<string>().domain([-cap, 0, cap]).range([DOWN, '#f7f7f7', UP]).clamp(true)\n\n\t\t// dendrograms (both axes)\n\t\tif (hm.rowDendrogram)\n\t\t\tdrawDendrogram(\n\t\t\t\tsvg.append('g').attr('transform', `translate(0,${gridY})`),\n\t\t\t\thm.rowDendrogram,\n\t\t\t\tcellH,\n\t\t\t\trowDendW,\n\t\t\t\t'left'\n\t\t\t)\n\t\tif (hm.colDendrogram)\n\t\t\tdrawDendrogram(\n\t\t\t\tsvg.append('g').attr('transform', `translate(${gridX},0)`),\n\t\t\t\thm.colDendrogram,\n\t\t\t\tcellW,\n\t\t\t\tcolDendH,\n\t\t\t\t'top'\n\t\t\t)\n\n\t\t// column labels \u2014 vertical (90\u00B0), reading upward from the grid\n\t\tconst labG = svg.append('g').attr('transform', `translate(${gridX},${gridY - 4})`)\n\t\tcols.forEach((c, i) => {\n\t\t\tconst cx = i * cellW + cellW / 2\n\t\t\tlabG\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', cx)\n\t\t\t\t.attr('y', 0)\n\t\t\t\t.attr('transform', `rotate(-90,${cx},0)`)\n\t\t\t\t.attr('text-anchor', 'start')\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.text(c)\n\t\t})\n\n\t\t// cells\n\t\tconst cg = svg.append('g').attr('transform', `translate(${gridX},${gridY})`)\n\t\tfor (let r = 0; r < rows.length; r++) {\n\t\t\tfor (let c = 0; c < cols.length; c++) {\n\t\t\t\tconst v = Z[r][c]\n\t\t\t\tcg.append('rect')\n\t\t\t\t\t.attr('x', c * cellW)\n\t\t\t\t\t.attr('y', r * cellH)\n\t\t\t\t\t.attr('width', cellW - 0.5)\n\t\t\t\t\t.attr('height', cellH - 0.5)\n\t\t\t\t\t.attr('fill', color(v))\n\t\t\t\t\t.on('mouseover', (event: any) => {\n\t\t\t\t\t\tthis.dom.tip.clear().show(event.clientX, event.clientY)\n\t\t\t\t\t\tthis.dom.tip.d\n\t\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t\t.style('padding', '5px 8px')\n\t\t\t\t\t\t\t.style('font-size', '0.85em')\n\t\t\t\t\t\t\t.html(\n\t\t\t\t\t\t\t\t`<b>${rows[r]}</b> \u2014 ${cols[c]}<br>z = ${v.toFixed(2)}, log2FC = ${hm.fc[r][c].toFixed(\n\t\t\t\t\t\t\t\t\t2\n\t\t\t\t\t\t\t\t)}, FDR = ${hm.fdr[r][c].toExponential(1)}`\n\t\t\t\t\t\t\t)\n\t\t\t\t\t})\n\t\t\t\t\t.on('mouseout', () => this.dom.tip.hide())\n\t\t\t}\n\t\t}\n\n\t\t// row labels (right of grid) \u2014 only when cells are tall enough; font scales with cell height\n\t\tif (showRowNames) {\n\t\t\tconst rowFont = Math.min(11, Math.max(7, Math.floor(cellH - 1)))\n\t\t\tconst rg = svg.append('g').attr('transform', `translate(${gridX + gridW + 4},${gridY})`)\n\t\t\trows.forEach((name, r) =>\n\t\t\t\trg\n\t\t\t\t\t.append('text')\n\t\t\t\t\t.attr('x', 0)\n\t\t\t\t\t.attr('y', r * cellH + cellH / 2)\n\t\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t\t.style('font-size', `${rowFont}px`)\n\t\t\t\t\t.text(name)\n\t\t\t)\n\t\t}\n\n\t\t// color legend \u2014 horizontal bar in the side panel, same font as gene labels\n\t\tconst legLen = 150\n\t\tconst legThick = 16\n\t\tconst steps = 24\n\t\tconst legSvg = legendHolder\n\t\t\t.append('svg')\n\t\t\t.attr('width', legLen + 8)\n\t\t\t.attr('height', legThick + 36)\n\t\t\t.attr('font-family', 'sans-serif')\n\t\tlegSvg\n\t\t\t.append('text')\n\t\t\t.attr('x', 0)\n\t\t\t.attr('y', 10)\n\t\t\t.style('font-size', '11px')\n\t\t\t.style('font-weight', '600')\n\t\t\t.text('log2FC-z')\n\t\tconst legG = legSvg.append('g').attr('transform', 'translate(2,18)')\n\t\tfor (let s = 0; s < steps; s++) {\n\t\t\tconst t = s / (steps - 1)\n\t\t\tlegG\n\t\t\t\t.append('rect')\n\t\t\t\t.attr('x', t * legLen)\n\t\t\t\t.attr('y', 0)\n\t\t\t\t.attr('width', legLen / steps + 0.6)\n\t\t\t\t.attr('height', legThick)\n\t\t\t\t.attr('fill', color(-cap + 2 * cap * t))\n\t\t}\n\t\tfor (const [t, lab] of [\n\t\t\t[0, `\u2212${cap.toFixed(1)}`],\n\t\t\t[0.5, '0'],\n\t\t\t[1, `+${cap.toFixed(1)}`]\n\t\t] as [number, string][])\n\t\t\tlegG\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', t * legLen)\n\t\t\t\t.attr('y', legThick + 13)\n\t\t\t\t.attr('text-anchor', t === 0 ? 'start' : t === 1 ? 'end' : 'middle')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.text(lab)\n\t}\n\n\t/** render a capped, expandable gene list (5 per row; first 10 shown, rest behind a black \"more\") */\n\trenderGeneList(holder: any, headerText: string, genes: string[]) {\n\t\tholder.selectAll('*').remove()\n\t\tholder.append('div').style('font-weight', '600').style('margin-bottom', '4px').text(headerText)\n\t\tconst list = holder\n\t\t\t.append('div')\n\t\t\t.style('max-width', '360px')\n\t\t\t.style('line-height', '1.6')\n\t\t\t.style('color', '#333')\n\t\t\t.style('word-break', 'break-word')\n\t\tconst LIMIT = 10\n\t\tconst PER_ROW = 5\n\t\tconst render = (expanded: boolean) => {\n\t\t\tlist.selectAll('*').remove()\n\t\t\tif (!genes.length) {\n\t\t\t\tlist.text('(none)')\n\t\t\t\treturn\n\t\t\t}\n\t\t\tconst shown = expanded ? genes : genes.slice(0, LIMIT)\n\t\t\tfor (let i = 0; i < shown.length; i += PER_ROW) {\n\t\t\t\tconst chunk = shown.slice(i, i + PER_ROW)\n\t\t\t\tconst last = i + PER_ROW >= shown.length\n\t\t\t\tlist.append('div').text(chunk.join(', ') + (last ? '' : ','))\n\t\t\t}\n\t\t\tif (genes.length > LIMIT)\n\t\t\t\tlist\n\t\t\t\t\t.append('button')\n\t\t\t\t\t.attr('type', 'button')\n\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t.style('color', '#333') // same color as the gene names, not a link color\n\t\t\t\t\t.style('text-decoration', 'underline')\n\t\t\t\t\t.style('display', 'inline-block')\n\t\t\t\t\t.style('margin-top', '3px')\n\t\t\t\t\t.style('background', 'none')\n\t\t\t\t\t.style('border', 'none')\n\t\t\t\t\t.style('padding', '0')\n\t\t\t\t\t.style('font', 'inherit')\n\t\t\t\t\t.text(expanded ? 'less' : `more (${(genes.length - LIMIT).toLocaleString()})`)\n\t\t\t\t\t.on('click', () => render(!expanded))\n\t\t}\n\t\trender(false)\n\t}\n\n\t/** age/progression trajectory. One section per ordered series; within a section, one small panel\n\t *  per k-means cluster: faint individual member trajectories (relative abundance)\n\t *  plus a thick black module-eigengene trend line. Click a panel to list that cluster's genes.\n\t *  DAP cutoffs + cluster count live in the right panel (all refetch). */\n\trenderTrajectory(traj: any) {\n\t\tconst body = this.dom.body\n\t\tif (!Array.isArray(traj) || !traj.length) {\n\t\t\tbody\n\t\t\t\t.append('div')\n\t\t\t\t.style('padding', '12px')\n\t\t\t\t.style('color', '#a00')\n\t\t\t\t.text(\n\t\t\t\t\t'No age/progression series in this selection \u2014 pick \u22653 cohorts that form one ordered series (same model/region/cell type, differing only by age or stage).'\n\t\t\t\t)\n\t\t\treturn\n\t\t}\n\t\tconst row = body.append('div').style('display', 'flex').style('gap', '24px').style('align-items', 'flex-start')\n\t\tconst left = row.append('div')\n\t\tconst panel = row.append('div').classed(PANEL_CLASS, true).style('font-size', '0.85em').style('min-width', '170px')\n\n\t\t// controls (all refetch, and reset the drill-down since cluster identities change)\n\t\tpanel.append('div').style('font-weight', '600').style('margin-bottom', '3px').text('DAP cutoffs')\n\t\tconst numInput = (label: string, value: number, step: number, title: string, onSet: (v: number) => void) => {\n\t\t\tconst l = panel.append('div').style('margin-bottom', '3px').attr('title', title)\n\t\t\tl.append('span').style('display', 'inline-block').style('width', '62px').html(label)\n\t\t\tl.append('input')\n\t\t\t\t.attr('type', 'number')\n\t\t\t\t.attr('step', step)\n\t\t\t\t.attr('min', 0)\n\t\t\t\t.property('value', value)\n\t\t\t\t.style('width', '60px')\n\t\t\t\t.on('change', (e: any) => {\n\t\t\t\t\tconst v = Number(e.target.value)\n\t\t\t\t\tif (Number.isFinite(v) && v >= 0) {\n\t\t\t\t\t\tonSet(v)\n\t\t\t\t\t\tthis.trajSelected = null\n\t\t\t\t\t\tthis.reload()\n\t\t\t\t\t}\n\t\t\t\t})\n\t\t}\n\t\tnumInput('|z| \u2265', this.zThresh, 0.5, 'Variable-protein fold-change cutoff', v => (this.zThresh = v))\n\t\tnumInput(\n\t\t\t'FDR \u2264',\n\t\t\tthis.fdrThresh,\n\t\t\t0.01,\n\t\t\t'Variable-protein significance cutoff (already an FDR)',\n\t\t\tv => (this.fdrThresh = v)\n\t\t)\n\t\tnumInput(\n\t\t\t'clusters',\n\t\t\tthis.nClusters,\n\t\t\t1,\n\t\t\t'Number of k-means clusters',\n\t\t\tv => (this.nClusters = Math.max(1, Math.round(v)))\n\t\t)\n\n\t\tpanel\n\t\t\t.append('div')\n\t\t\t.style('margin-top', '10px')\n\t\t\t.style('font-size', '0.8em')\n\t\t\t.style('color', '#777')\n\t\t\t.style('line-height', '1.4')\n\t\t\t.html(\n\t\t\t\t'Each thin line is one protein (standardized log2FC-z).<br>The thick black line is the cluster eigengene (PC1).'\n\t\t\t)\n\n\t\tconst genePanel = panel.append('div').style('margin-top', '14px')\n\t\tconst showGenes = () => {\n\t\t\tconst selSi = this.trajSelected?.si\n\t\t\tconst s = selSi != null ? traj[selSi] : null\n\t\t\tconst pr = s?.clusters?.[this.trajSelected!.pi]\n\t\t\tif (!pr) {\n\t\t\t\tgenePanel.selectAll('*').remove()\n\t\t\t\tgenePanel.append('div').style('color', '#888').text('Click a cluster to list its proteins.')\n\t\t\t\treturn\n\t\t\t}\n\t\t\tthis.renderGeneList(\n\t\t\t\tgenePanel,\n\t\t\t\t`${pr.size.toLocaleString()} proteins \u00B7 ${s!.label} \u00B7 C${this.trajSelected!.pi + 1}:`,\n\t\t\t\tpr.genes\n\t\t\t)\n\t\t}\n\n\t\tconst renderAll = () => {\n\t\t\tleft.selectAll('*').remove()\n\t\t\ttraj.forEach((s: any, si: number) => {\n\t\t\t\tconst section = left.append('div').style('margin-bottom', '20px')\n\t\t\t\tsection.append('div').style('font-weight', '600').style('max-width', '640px').text(s.label)\n\t\t\t\tsection\n\t\t\t\t\t.append('div')\n\t\t\t\t\t.style('font-size', '0.8em')\n\t\t\t\t\t.style('color', '#888')\n\t\t\t\t\t.style('margin-bottom', '6px')\n\t\t\t\t\t.text(\n\t\t\t\t\t\t`${(s.geneCount || 0).toLocaleString()} variable proteins \u00B7 ${s.points\n\t\t\t\t\t\t\t.map((p: any) => p.label)\n\t\t\t\t\t\t\t.join(' \u2192 ')}`\n\t\t\t\t\t)\n\t\t\t\tconst grid = section.append('div').style('display', 'flex').style('flex-wrap', 'wrap').style('gap', '12px')\n\t\t\t\tif (!s.clusters?.length) {\n\t\t\t\t\tgrid\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.style('color', '#a00')\n\t\t\t\t\t\t.style('font-size', '0.85em')\n\t\t\t\t\t\t.text('No variable proteins at these cutoffs.')\n\t\t\t\t\treturn\n\t\t\t\t}\n\t\t\t\ts.clusters.forEach((pr: any, pi: number) => {\n\t\t\t\t\tconst selected = this.trajSelected != null && this.trajSelected.si === si && this.trajSelected.pi === pi\n\t\t\t\t\tconst cell = grid\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.style('border', selected ? '2px solid #333' : '1px solid #ddd')\n\t\t\t\t\t\t.style('border-radius', '4px')\n\t\t\t\t\t\t.style('padding', '4px 6px 2px')\n\t\t\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t\t\t.on('click', () => {\n\t\t\t\t\t\t\tthis.trajSelected = selected ? null : { si, pi }\n\t\t\t\t\t\t\trenderAll()\n\t\t\t\t\t\t\tshowGenes()\n\t\t\t\t\t\t})\n\t\t\t\t\tcell\n\t\t\t\t\t\t.append('div')\n\t\t\t\t\t\t.style('font-size', '0.8em')\n\t\t\t\t\t\t.style('font-weight', selected ? '700' : '600')\n\t\t\t\t\t\t.style('margin-bottom', '1px')\n\t\t\t\t\t\t.text(`C${pi + 1} \u00B7 ${pr.size.toLocaleString()} proteins`)\n\t\t\t\t\tthis.drawClusterPlot(cell.append('div'), s.points, pr)\n\t\t\t\t})\n\t\t\t})\n\t\t}\n\t\trenderAll()\n\t\tshowGenes()\n\t}\n\n\t/** one cluster panel: faint member trajectories + a thick black eigengene line, over the ordered\n\t *  timepoints (true-spaced by age). y = relative abundance (standardized log2FC-z). */\n\tdrawClusterPlot(holder: any, points: { value: number; label: string }[], cluster: any) {\n\t\tconst lines: number[][] = cluster.lines || []\n\t\tconst eigengene: number[] = cluster.eigengene || []\n\t\tconst W = 232,\n\t\t\tH = 162\n\t\tconst M = { top: 8, right: 10, bottom: 34, left: 44 }\n\t\tconst innerW = W - M.left - M.right\n\t\tconst innerH = H - M.top - M.bottom\n\t\tconst xs = points.map(p => p.value)\n\t\tconst xmin = Math.min(...xs)\n\t\tconst xmax = Math.max(...xs)\n\n\t\tlet ymin = Infinity,\n\t\t\tymax = -Infinity\n\t\tfor (const ln of lines)\n\t\t\tfor (const v of ln) {\n\t\t\t\tif (v < ymin) ymin = v\n\t\t\t\tif (v > ymax) ymax = v\n\t\t\t}\n\t\tfor (const v of eigengene) {\n\t\t\tif (v < ymin) ymin = v\n\t\t\tif (v > ymax) ymax = v\n\t\t}\n\t\tif (!Number.isFinite(ymin)) {\n\t\t\tymin = -2\n\t\t\tymax = 2\n\t\t}\n\t\tif (ymin === ymax) {\n\t\t\tymin -= 1\n\t\t\tymax += 1\n\t\t}\n\t\tconst padY = (ymax - ymin) * 0.06\n\t\tconst x = scaleLinear()\n\t\t\t.domain([xmin, xmax])\n\t\t\t.range([M.left, M.left + innerW])\n\t\tconst y = scaleLinear()\n\t\t\t.domain([ymin - padY, ymax + padY])\n\t\t\t.range([M.top + innerH, M.top])\n\n\t\tconst svg = holder.append('svg').attr('width', W).attr('height', H).attr('font-family', 'sans-serif')\n\t\tif (ymin < 0 && ymax > 0)\n\t\t\tsvg\n\t\t\t\t.append('line')\n\t\t\t\t.attr('x1', M.left)\n\t\t\t\t.attr('x2', M.left + innerW)\n\t\t\t\t.attr('y1', y(0))\n\t\t\t\t.attr('y2', y(0))\n\t\t\t\t.attr('stroke', '#eee')\n\t\tsvg\n\t\t\t.append('g')\n\t\t\t.attr('transform', `translate(0,${M.top + innerH})`)\n\t\t\t.call(\n\t\t\t\taxisBottom(x)\n\t\t\t\t\t.tickValues(xs)\n\t\t\t\t\t.tickFormat(((_d: any, i: number) => points[i]?.label ?? '') as any) as any\n\t\t\t)\n\t\tsvg\n\t\t\t.append('g')\n\t\t\t.attr('transform', `translate(${M.left},0)`)\n\t\t\t.call(axisLeft(y).ticks(3) as any)\n\n\t\t// axis labels: x = age (ticks are the ages), y = relative abundance (standardized log2FC-z)\n\t\tsvg\n\t\t\t.append('text')\n\t\t\t.attr('x', M.left + innerW / 2)\n\t\t\t.attr('y', H - 3)\n\t\t\t.attr('text-anchor', 'middle')\n\t\t\t.style('font-size', '9px')\n\t\t\t.style('fill', '#555')\n\t\t\t.text('age')\n\t\tsvg\n\t\t\t.append('text')\n\t\t\t.attr('transform', `translate(9,${M.top + innerH / 2}) rotate(-90)`)\n\t\t\t.attr('text-anchor', 'middle')\n\t\t\t.style('font-size', '9px')\n\t\t\t.style('fill', '#555')\n\t\t\t.text('relative abundance')\n\n\t\tconst pathOf = (vec: number[]) => vec.map((v, i) => `${i ? 'L' : 'M'}${x(points[i].value)},${y(v)}`).join(' ')\n\n\t\t// faint individual member trajectories\n\t\tfor (const ln of lines)\n\t\t\tsvg\n\t\t\t\t.append('path')\n\t\t\t\t.attr('d', pathOf(ln))\n\t\t\t\t.attr('fill', 'none')\n\t\t\t\t.attr('stroke', '#888')\n\t\t\t\t.attr('stroke-width', 0.5)\n\t\t\t\t.attr('stroke-opacity', 0.22)\n\t\t// thick black eigengene trend\n\t\tif (eigengene.length)\n\t\t\tsvg\n\t\t\t\t.append('path')\n\t\t\t\t.attr('d', pathOf(eigengene))\n\t\t\t\t.attr('fill', 'none')\n\t\t\t\t.attr('stroke', '#000')\n\t\t\t\t.attr('stroke-width', 2.5)\n\t}\n\n\t/** shared-vs-specific DAP overlap: an UpSet plot per direction (only offered for \u22653 cohorts).\n\t *  Each protein falls in exactly one combination \u2014 the set of cohorts where it's a DAP in that\n\t *  direction (|z| \u2265 zThresh, FDR \u2264 fdrThresh). Single-cohort groups are cohort-specific. */\n\trenderOverlap(overlap: any) {\n\t\tif (!overlap || !Array.isArray(overlap.up) || !Array.isArray(overlap.down)) {\n\t\t\tthis.dom.body.append('div').style('padding', '12px').style('color', '#a00').text('Overlap unavailable.')\n\t\t\treturn\n\t\t}\n\t\tconst labels = this.cohorts.map(c => this.cohortLabel(c))\n\t\tconst wrap = this.dom.body.append('div')\n\n\t\t// plots on the left, DAP-cutoff controls on the right\n\t\tconst row = wrap.append('div').style('display', 'flex').style('gap', '24px').style('align-items', 'flex-start')\n\t\tconst left = row.append('div')\n\t\tconst panel = row.append('div').classed(PANEL_CLASS, true).style('font-size', '0.85em').style('min-width', '150px')\n\n\t\t// DAP-cutoff controls (shared with the other views) \u2014 changing refetches\n\t\tpanel.append('div').style('font-weight', '600').style('margin-bottom', '3px').text('DAP cutoffs')\n\t\tconst numInput = (label: string, value: number, step: number, title: string, onSet: (v: number) => void) => {\n\t\t\tconst l = panel.append('div').style('margin-bottom', '3px').attr('title', title)\n\t\t\tl.append('span').style('display', 'inline-block').style('width', '48px').html(label)\n\t\t\tl.append('input')\n\t\t\t\t.attr('type', 'number')\n\t\t\t\t.attr('step', step)\n\t\t\t\t.attr('min', 0)\n\t\t\t\t.property('value', value)\n\t\t\t\t.style('width', '64px')\n\t\t\t\t.on('change', (e: any) => {\n\t\t\t\t\tconst v = Number(e.target.value)\n\t\t\t\t\tif (Number.isFinite(v) && v >= 0) {\n\t\t\t\t\t\tonSet(v)\n\t\t\t\t\t\tthis.reload()\n\t\t\t\t\t}\n\t\t\t\t})\n\t\t}\n\t\tnumInput('|z| \u2265', this.zThresh, 0.5, 'DAP fold-change cutoff', v => (this.zThresh = v))\n\t\tnumInput('FDR \u2264', this.fdrThresh, 0.01, 'DAP significance cutoff (FDR)', v => (this.fdrThresh = v))\n\n\t\tconst diagrams = left.append('div')\n\n\t\t// gene-list panel (right side, under the cutoffs), filled on click; first 10 shown, rest behind \"more\"\n\t\tconst genePanel = panel.append('div').style('margin-top', '16px')\n\t\tconst cohortPhrase = (idxs: number[]) => {\n\t\t\tconst names = idxs.map(i => labels[i])\n\t\t\tif (names.length <= 1) return names[0] || '\u2014'\n\t\t\tif (names.length === 2) return `${names[0]} and ${names[1]}`\n\t\t\treturn `${names.slice(0, -1).join(', ')}, and ${names[names.length - 1]}`\n\t\t}\n\t\tconst showGenes = (dir: string, combo: { cohorts: number[]; genes: string[] }) => {\n\t\t\tconst cnt = combo.genes.length\n\t\t\tthis.renderGeneList(\n\t\t\t\tgenePanel,\n\t\t\t\t`${cnt.toLocaleString()} protein${cnt === 1 ? '' : 's'} ${dir.toLowerCase()} in ${cohortPhrase(\n\t\t\t\t\tcombo.cohorts\n\t\t\t\t)}:`,\n\t\t\t\tcombo.genes\n\t\t\t)\n\t\t}\n\n\t\t// one UpSet per direction, stacked (up above down)\n\t\tfor (const [dir, combos] of [\n\t\t\t['Up-regulated', overlap.up],\n\t\t\t['Down-regulated', overlap.down]\n\t\t] as [string, any[]][]) {\n\t\t\tconst box = diagrams.append('div').style('margin-bottom', '24px')\n\t\t\tbox\n\t\t\t\t.append('div')\n\t\t\t\t.style('font-weight', '600')\n\t\t\t\t.style('margin-bottom', '4px')\n\t\t\t\t.text(`${dir} (${totalGenes(combos).toLocaleString()})`)\n\t\t\tthis.drawUpSet(box, combos, labels, dir, showGenes)\n\t\t}\n\t}\n\n\t/** UpSet plot: intersection-size bars over a cohort-membership dot matrix. Bars clickable. */\n\tdrawUpSet(\n\t\tcontainer: any,\n\t\tcombos: { cohorts: number[]; genes: string[] }[],\n\t\tlabels: string[],\n\t\tdir: string,\n\t\tshowGenes: (dir: string, combo: { cohorts: number[]; genes: string[] }) => void\n\t) {\n\t\tconst n = labels.length\n\t\tconst MAX_COLS = 22\n\t\tconst shown = combos.slice(0, MAX_COLS)\n\t\tif (!shown.length) {\n\t\t\tcontainer.append('div').style('color', '#a00').style('padding', '8px 0').text('No DAPs at these cutoffs.')\n\t\t\treturn\n\t\t}\n\t\tconst maxCount = Math.max(1, ...shown.map(c => c.genes.length))\n\t\tconst leftW = 150,\n\t\t\ttopPad = 14,\n\t\t\tbarMaxH = 110,\n\t\t\tcolW = 26,\n\t\t\trowH = 15,\n\t\t\tdotR = 4.5\n\t\tconst matrixTop = topPad + barMaxH + 14\n\t\tconst W = leftW + shown.length * colW + 12\n\t\tconst H = matrixTop + n * rowH + 8\n\t\tconst svg = container.append('svg').attr('width', W).attr('height', H).attr('font-family', 'sans-serif')\n\t\tconst barColor = dir[0] === 'U' ? UP : DOWN\n\n\t\t// per-cohort total DAP count (set size), over ALL combos (not just the shown ones)\n\t\tconst totals = labels.map((_, i) => combos.reduce((s, c) => s + (c.cohorts.includes(i) ? c.genes.length : 0), 0))\n\t\tconst yBar = scaleLinear().domain([0, maxCount]).range([0, barMaxH])\n\n\t\t// cohort rows (left labels + zebra background)\n\t\tfor (let i = 0; i < n; i++) {\n\t\t\tsvg\n\t\t\t\t.append('rect')\n\t\t\t\t.attr('x', leftW - 6)\n\t\t\t\t.attr('y', matrixTop + i * rowH)\n\t\t\t\t.attr('width', shown.length * colW + 6)\n\t\t\t\t.attr('height', rowH)\n\t\t\t\t.attr('fill', i % 2 ? '#f4f4f4' : '#fff')\n\t\t\tsvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', leftW - 10)\n\t\t\t\t.attr('y', matrixTop + i * rowH + rowH / 2)\n\t\t\t\t.attr('text-anchor', 'end')\n\t\t\t\t.attr('dominant-baseline', 'central')\n\t\t\t\t.style('font-size', '11px')\n\t\t\t\t.text(`${labels[i]} (${totals[i].toLocaleString()})`)\n\t\t}\n\n\t\tshown.forEach((combo, j) => {\n\t\t\tconst x = leftW + j * colW + colW / 2\n\t\t\tconst cnt = combo.genes.length\n\t\t\tconst barH = yBar(cnt)\n\t\t\tconst members = new Set(combo.cohorts)\n\t\t\tconst tip = `${combo.cohorts.map(i => labels[i]).join(' \u2229 ')}: ${cnt} proteins \u2014 click to list`\n\n\t\t\t// intersection bar\n\t\t\tsvg\n\t\t\t\t.append('rect')\n\t\t\t\t.attr('x', x - colW * 0.34)\n\t\t\t\t.attr('y', topPad + barMaxH - barH)\n\t\t\t\t.attr('width', colW * 0.68)\n\t\t\t\t.attr('height', Math.max(1, barH))\n\t\t\t\t.attr('fill', barColor)\n\t\t\t\t.attr('fill-opacity', 0.85)\n\t\t\tsvg\n\t\t\t\t.append('text')\n\t\t\t\t.attr('x', x)\n\t\t\t\t.attr('y', topPad + barMaxH - barH - 3)\n\t\t\t\t.attr('text-anchor', 'middle')\n\t\t\t\t.style('font-size', '9px')\n\t\t\t\t.style('fill', '#333')\n\t\t\t\t.text(cnt.toLocaleString())\n\n\t\t\t// membership connector line\n\t\t\tif (combo.cohorts.length > 1)\n\t\t\t\tsvg\n\t\t\t\t\t.append('line')\n\t\t\t\t\t.attr('x1', x)\n\t\t\t\t\t.attr('x2', x)\n\t\t\t\t\t.attr('y1', matrixTop + Math.min(...combo.cohorts) * rowH + rowH / 2)\n\t\t\t\t\t.attr('y2', matrixTop + Math.max(...combo.cohorts) * rowH + rowH / 2)\n\t\t\t\t\t.attr('stroke', '#444')\n\t\t\t\t\t.attr('stroke-width', 1.5)\n\t\t\tfor (let i = 0; i < n; i++)\n\t\t\t\tsvg\n\t\t\t\t\t.append('circle')\n\t\t\t\t\t.attr('cx', x)\n\t\t\t\t\t.attr('cy', matrixTop + i * rowH + rowH / 2)\n\t\t\t\t\t.attr('r', dotR)\n\t\t\t\t\t.attr('fill', members.has(i) ? '#444' : '#d0d0d0')\n\n\t\t\t// transparent full-column hit area (small bars are otherwise hard to click)\n\t\t\tconst hit = svg\n\t\t\t\t.append('rect')\n\t\t\t\t.attr('x', x - colW / 2)\n\t\t\t\t.attr('y', topPad)\n\t\t\t\t.attr('width', colW)\n\t\t\t\t.attr('height', H - topPad)\n\t\t\t\t.attr('fill', 'transparent')\n\t\t\t\t.style('cursor', 'pointer')\n\t\t\t\t.on('click', () => showGenes(dir, combo))\n\t\t\thit.append('title').text(tip)\n\t\t})\n\n\t\tif (combos.length > shown.length)\n\t\t\tcontainer\n\t\t\t\t.append('div')\n\t\t\t\t.style('font-size', '0.8em')\n\t\t\t\t.style('color', '#999')\n\t\t\t\t.style('margin-top', '2px')\n\t\t\t\t.text(`Showing the ${shown.length} largest of ${combos.length.toLocaleString()} intersections.`)\n\t}\n}\n\ntype Hclust = {\n\tmerge: { n1: number; n2: number }[]\n\theight: { height: number }[]\n\torder: { name: string }[]\n\tinputOrder: string[]\n}\n\n/** draw an hclust dendrogram into <g>. orient 'left' \u2192 leaves along y (row dendrogram, branches\n *  grow leftward); orient 'top' \u2192 leaves along x (column dendrogram, branches grow upward).\n *  leafSize = px per leaf (cell height/width); depth = px available for the height axis. */\nfunction drawDendrogram(g: any, dend: Hclust, leafSize: number, depth: number, orient: 'left' | 'top') {\n\tconst heights = dend.height.map(h => h.height)\n\tconst maxH = Math.max(...heights, 1e-9)\n\tconst toDepth = scaleLinear().domain([0, maxH]).range([depth, 0])\n\tconst leafPos = new Map<string, number>()\n\tdend.order.forEach((leaf, i) => leafPos.set(leaf.name, i * leafSize + leafSize / 2))\n\tconst merged = new Map<number, { leaf: number; depth: number }>()\n\tconst pos = (n: number) =>\n\t\tn < 0 ? { leaf: leafPos.get(dend.inputOrder[-n - 1]) ?? 0, depth } : merged.get(n) || { leaf: 0, depth }\n\tconst seg = (l1: number, d1: number, l2: number, d2: number) => {\n\t\tconst [x1, y1, x2, y2] = orient === 'left' ? [d1, l1, d2, l2] : [l1, d1, l2, d2]\n\t\tg.append('line')\n\t\t\t.attr('x1', x1)\n\t\t\t.attr('y1', y1)\n\t\t\t.attr('x2', x2)\n\t\t\t.attr('y2', y2)\n\t\t\t.attr('stroke', '#555')\n\t\t\t.attr('stroke-width', 1)\n\t}\n\tfor (let i = 0; i < dend.merge.length; i++) {\n\t\tconst { n1, n2 } = dend.merge[i]\n\t\tconst a = pos(n1),\n\t\t\tb = pos(n2)\n\t\tconst d = toDepth(heights[i])\n\t\tseg(a.leaf, a.depth, a.leaf, d)\n\t\tseg(b.leaf, b.depth, b.leaf, d)\n\t\tseg(a.leaf, d, b.leaf, d)\n\t\tmerged.set(i + 1, { leaf: (a.leaf + b.leaf) / 2, depth: d })\n\t}\n}\n\n/** average-linkage agglomerative clustering \u2192 leaf order (distance = 1 \u2212 correlation). n is small. */\nfunction leafOrder(corr: number[][]): number[] {\n\tconst n = corr.length\n\tconst nodes: { members: number[] }[] = []\n\tfor (let i = 0; i < n; i++) nodes.push({ members: [i] })\n\tlet active = nodes.map((_, i) => i)\n\tconst d0 = (i: number, j: number) => 1 - corr[i][j]\n\tconst avgDist = (a: number, b: number) => {\n\t\tlet s = 0\n\t\tfor (const x of nodes[a].members) for (const y of nodes[b].members) s += d0(x, y)\n\t\treturn s / (nodes[a].members.length * nodes[b].members.length)\n\t}\n\twhile (active.length > 1) {\n\t\tlet bi = 0,\n\t\t\tbj = 1,\n\t\t\tbd = Infinity\n\t\tfor (let a = 0; a < active.length; a++)\n\t\t\tfor (let b = a + 1; b < active.length; b++) {\n\t\t\t\tconst d = avgDist(active[a], active[b])\n\t\t\t\tif (d < bd) {\n\t\t\t\t\tbd = d\n\t\t\t\t\tbi = a\n\t\t\t\t\tbj = b\n\t\t\t\t}\n\t\t\t}\n\t\tconst A = active[bi],\n\t\t\tB = active[bj]\n\t\tnodes.push({ members: [...nodes[A].members, ...nodes[B].members] })\n\t\tactive = active.filter((_, k) => k !== bi && k !== bj)\n\t\tactive.push(nodes.length - 1)\n\t}\n\treturn nodes[active[0]].members\n}\n\n/** total DAP proteins across all combinations of one direction (each protein is in exactly one) */\nfunction totalGenes(combos: { genes: string[] }[]): number {\n\treturn combos.reduce((s, c) => s + c.genes.length, 0)\n}\n\nexport const componentInit = getCompInit(ProteomeCohortCompare)\n\nexport async function getPlotConfig(opts: any) {\n\tconst config = structuredClone(defaultConfig)\n\tif (!opts.cohorts || opts.cohorts.length < 2) throw new Error('proteomeCohortCompare requires \u22652 cohorts')\n\treturn copyMerge(config, opts)\n}\n"],
+  "mappings": 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+  "names": []
+}

package/dist/pseudbulk.unit.spec-UVVRP6NR.js

@@ -0,0 +1,82 @@
+import {
+  require_tape
+} from "./chunk-PJYCTAMC.js";
+import {
+  SearchHandler,
+  createPseudobulkTerm
+} from "./chunk-AJXP4AV7.js";
+import "./chunk-NNDKYTUV.js";
+import "./chunk-HJ6L54YS.js";
+import "./chunk-HWNQOADC.js";
+import "./chunk-CNFTQSNE.js";
+import "./chunk-PLFPXOGX.js";
+import "./chunk-EEB5VE2A.js";
+import "./chunk-3CIL7KH7.js";
+import "./chunk-T4XPCSLP.js";
+import "./chunk-BIJOXCLN.js";
+import "./chunk-W5J3LTYS.js";
+import "./chunk-L2WOLNZK.js";
+import "./chunk-AMW5LCUB.js";
+import "./chunk-ZPWBYHNE.js";
+import "./chunk-HBNB5TRH.js";
+import "./chunk-PF4DSFDR.js";
+import "./chunk-4OLM3KSB.js";
+import "./chunk-6XKAOSQE.js";
+import "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import "./chunk-I6Y4O3RR.js";
+import "./chunk-Q5RDQNIT.js";
+import {
+  __toESM
+} from "./chunk-HS5PO5ZQ.js";
+
+// termdb/handlers/test/pseudbulk.unit.spec.ts
+var import_tape = __toESM(require_tape(), 1);
+(0, import_tape.default)("\n", function(test) {
+  test.comment("-***- termdb/handlers/pseudobulk -***-");
+  test.end();
+});
+(0, import_tape.default)("buildRenderingDataMap() groups terms by assay and memberId", function(test) {
+  const handler = new SearchHandler();
+  const terms = [
+    { id: "t1", name: "A", assay: "geneExpression", memberId: "CD4" },
+    { id: "t2", name: "B", assay: "geneExpression", memberId: "CD4" },
+    { id: "t3", name: "C", assay: "geneExpression", memberId: "CD8" },
+    { id: "t4", name: "D", assay: "cellType", memberId: "Myeloid" }
+  ];
+  const map = handler.buildRenderingDataMap(terms);
+  test.equal(map.size, 2, "creates one top-level key per assay");
+  test.ok(map.has("geneExpression"), "contains geneExpression assay");
+  test.ok(map.has("cellType"), "contains cellType assay");
+  const geneExpressionMap = map.get("geneExpression");
+  test.equal(geneExpressionMap.size, 2, "creates one nested key per memberId within assay");
+  test.equal(geneExpressionMap.get("CD4").length, 2, "groups multiple terms under same assay/memberId");
+  test.equal(geneExpressionMap.get("CD8")[0].id, "t3", "stores the correct term under another memberId");
+  const cellTypeMap = map.get("cellType");
+  test.equal(cellTypeMap.size, 1, "cellType assay has one memberId");
+  test.equal(cellTypeMap.get("Myeloid")[0].id, "t4", "stores term under expected cellType memberId");
+  test.end();
+});
+(0, import_tape.default)("buildRenderingDataMap() returns an empty map for empty input", function(test) {
+  const handler = new SearchHandler();
+  const map = handler.buildRenderingDataMap([]);
+  test.equal(map.size, 0, "empty input produces empty map");
+  test.end();
+});
+(0, import_tape.default)("createPseudobulkTerm() creates one term for one cell type and gene", function(test) {
+  const selectedTerm = {
+    id: "blast",
+    name: "Blast",
+    type: "pseudobulk",
+    assay: "geneExpression",
+    memberId: "Cell Type"
+  };
+  const term = createPseudobulkTerm(selectedTerm, "TP53");
+  test.equal(term.id, "geneExpression blast TP53", "sets a unique term.id");
+  test.equal(term.category, "blast", "sets term.category");
+  test.equal(term.gene, "TP53", "sets term.gene");
+  test.equal(term.name, "geneExpression blast TP53", "sets term.name");
+  test.notOk("genes" in term, "does not add the obsolete genes array");
+  test.end();
+});
+//# sourceMappingURL=pseudbulk.unit.spec-UVVRP6NR.js.map

package/dist/pseudobulk-ZIN5VJGB.js

@@ -0,0 +1,31 @@
+import {
+  SearchHandler,
+  createPseudobulkTerm
+} from "./chunk-AJXP4AV7.js";
+import "./chunk-NNDKYTUV.js";
+import "./chunk-HJ6L54YS.js";
+import "./chunk-HWNQOADC.js";
+import "./chunk-CNFTQSNE.js";
+import "./chunk-PLFPXOGX.js";
+import "./chunk-EEB5VE2A.js";
+import "./chunk-3CIL7KH7.js";
+import "./chunk-T4XPCSLP.js";
+import "./chunk-BIJOXCLN.js";
+import "./chunk-W5J3LTYS.js";
+import "./chunk-L2WOLNZK.js";
+import "./chunk-AMW5LCUB.js";
+import "./chunk-ZPWBYHNE.js";
+import "./chunk-HBNB5TRH.js";
+import "./chunk-PF4DSFDR.js";
+import "./chunk-4OLM3KSB.js";
+import "./chunk-6XKAOSQE.js";
+import "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import "./chunk-I6Y4O3RR.js";
+import "./chunk-Q5RDQNIT.js";
+import "./chunk-HS5PO5ZQ.js";
+export {
+  SearchHandler,
+  createPseudobulkTerm
+};
+//# sourceMappingURL=pseudobulk-ZIN5VJGB.js.map

package/dist/qualitative-27BZGASV.js

@@ -0,0 +1,34 @@
+import {
+  QualCustomGS,
+  QualPredefinedGS,
+  QualValues,
+  QualitativeBase
+} from "./chunk-NNDKYTUV.js";
+import "./chunk-HJ6L54YS.js";
+import "./chunk-HWNQOADC.js";
+import "./chunk-CNFTQSNE.js";
+import "./chunk-PLFPXOGX.js";
+import "./chunk-EEB5VE2A.js";
+import "./chunk-3CIL7KH7.js";
+import "./chunk-T4XPCSLP.js";
+import "./chunk-BIJOXCLN.js";
+import "./chunk-W5J3LTYS.js";
+import "./chunk-L2WOLNZK.js";
+import "./chunk-AMW5LCUB.js";
+import "./chunk-ZPWBYHNE.js";
+import "./chunk-HBNB5TRH.js";
+import "./chunk-PF4DSFDR.js";
+import "./chunk-4OLM3KSB.js";
+import "./chunk-6XKAOSQE.js";
+import "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import "./chunk-I6Y4O3RR.js";
+import "./chunk-Q5RDQNIT.js";
+import "./chunk-HS5PO5ZQ.js";
+export {
+  QualCustomGS,
+  QualPredefinedGS,
+  QualValues,
+  QualitativeBase
+};
+//# sourceMappingURL=qualitative-27BZGASV.js.map

package/dist/qualitative-N4F6NITI.js

@@ -0,0 +1,241 @@
+import {
+  HandlerBase,
+  require_debounce
+} from "./chunk-NNDKYTUV.js";
+import "./chunk-HJ6L54YS.js";
+import "./chunk-HWNQOADC.js";
+import "./chunk-CNFTQSNE.js";
+import "./chunk-PLFPXOGX.js";
+import "./chunk-EEB5VE2A.js";
+import "./chunk-3CIL7KH7.js";
+import "./chunk-T4XPCSLP.js";
+import "./chunk-BIJOXCLN.js";
+import "./chunk-W5J3LTYS.js";
+import "./chunk-L2WOLNZK.js";
+import "./chunk-AMW5LCUB.js";
+import "./chunk-ZPWBYHNE.js";
+import "./chunk-HBNB5TRH.js";
+import "./chunk-PF4DSFDR.js";
+import "./chunk-4OLM3KSB.js";
+import "./chunk-6XKAOSQE.js";
+import "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import {
+  select_default
+} from "./chunk-I6Y4O3RR.js";
+import "./chunk-Q5RDQNIT.js";
+import {
+  __toESM
+} from "./chunk-HS5PO5ZQ.js";
+
+// termsetting/handlers/qualitative.ts
+var import_debounce = __toESM(require_debounce(), 1);
+var GroupSet = class extends HandlerBase {
+  constructor(opts) {
+    super(opts);
+    this.defaultMaxGrpNum = 5;
+    this.minGrpNum = 3;
+    //{groups: any[], values: any[]}
+    this.dom = {};
+    this.termsetting = opts.termsetting;
+    this.tw = opts.termsetting.tw;
+    this.dom.holder = opts.holder || this.termsetting.dom.tip.d;
+    this.data = { groups: [], values: [], filters: [] };
+  }
+  getPillStatus() {
+    this.tw = this.termsetting.tw;
+    return this.tw.getStatus(this.termsetting.usecase);
+  }
+  async showEditMenu() {
+    const self = this.termsetting;
+    const holder = this.dom.holder;
+    this.dom.loadingDiv = holder.append("div").style("margin", "15px").text("Getting categories...");
+    this.dom.menuWrapper = holder.append("div");
+    const body = self.opts.getBodyParams?.() || {};
+    const data = await self.vocabApi.getCategories(self.term, self.filter, body);
+    this.dom.loadingDiv.style("display", "none");
+    this.category2samplecount = data.lst;
+    this.tw = this.termsetting.tw;
+    this.data = this.tw.getGroups(this.category2samplecount);
+    await this.initGrpSetUI();
+  }
+  async initGrpSetUI() {
+    const self = this.termsetting;
+    this.maxGrpNum = this.data.values.length >= this.defaultMaxGrpNum ? this.defaultMaxGrpNum + 1 : this.data.values.length;
+    self.dom.tip.showunder(self.dom.holder.node());
+    await this.showDraggables();
+  }
+  async showDraggables() {
+    const self = this.termsetting;
+    this.dom.menuWrapper.style("padding", "10px");
+    this.dom.actionDiv = this.dom.menuWrapper.append("div").attr("class", "sjpp-group-actions").style("padding", "0px 10px 10px 0px");
+    const findNewGrps = this.data.groups.filter((g) => g.name.startsWith("New Group"));
+    let newGrpNum = findNewGrps.length > 0 ? findNewGrps[findNewGrps.length - 1].name.replace(`New Group `, "") : 0;
+    const q = this.tw.q;
+    this.dom.actionDiv.addGroup = this.dom.actionDiv.append("button").classed("sjpp_grpset_addGrp_btn", true).style("display", "inline-block").style("text-align", "center").style("cursor", q.mode == "binary" ? "default" : "pointer").property("disabled", q.mode == "binary" ? true : this.data.groups.length >= this.maxGrpNum).text("Add Group").on("click", async () => {
+      newGrpNum++;
+      this.data.groups.push({
+        currentIdx: this.data.groups.length,
+        type: "values",
+        name: `New Group${newGrpNum != 1 ? ` ${newGrpNum}` : ""}`
+      });
+      const group = this.data.groups[this.data.groups.length - 1];
+      await this.initGroupDiv(group);
+      await this.update();
+    });
+    this.dom.actionDiv.applyBtn = this.dom.actionDiv.append("button").classed("sjpp_grpset_apply_btn", true).style("display", self.opts.hideApply ? "none" : "inline-block").style("text-align", "center").style("float", "right").style("cursor", "pointer").text("Apply").on("click", () => {
+      this.processDraggables();
+      self.dom.tip.hide();
+      self.api.runCallback();
+    });
+    this.dom.menuWrapper.append("div").style("display", "block").style("margin", "5px 2px").style("font-size", ".6em").style("color", "#999").text("Drag-and-drop to assign categories to groups.");
+    this.dom.grpsWrapper = this.dom.menuWrapper.append("div").classed("sjpp-groups-wrapper", true);
+    this.dom.includedWrapper = this.dom.grpsWrapper.append("div").classed("sjpp-groups-include", true).classed("sjpp-group-edit-div", true).style("display", "flex");
+    this.dom.excludedWrapper = this.dom.grpsWrapper.append("div").classed("sjpp-groups-exclude", true).classed("sjpp-group-edit-div", true).classed("sjpp-drag-drop-div", true);
+    const excludedGroup = this.data.groups.find((d) => d.currentIdx === 0);
+    delete excludedGroup.wrapper;
+    await this.initGroupDiv(excludedGroup);
+    const handler = this;
+    await this.dom.includedWrapper.selectAll("div").data(this.data.groups.filter((d) => d.currentIdx != 0)).enter().append("div").classed("sjpp-drag-drop-div", true).style("border", "1px solid #efefef").style("display", "block").style("padding", "10px").style("vertical-align", "top").each(async function(group) {
+      group.wrapper = select_default(this);
+      await handler.initGroupDiv(group);
+    });
+  }
+  processDraggables() {
+    const self = this.termsetting;
+    const editedGrpset = this.draggedItem || this.editedName || this.removedGrp;
+    if (!editedGrpset) return;
+    const customset = { groups: [] };
+    for (const group of this.data.groups) {
+      if (group.type != "values" && group.type != "QualTWValues" && group.type != "QualTWValues")
+        throw `group.type='${group.type}' is not recognized`;
+      const customgroup = { name: group.name, type: "values", uncomputable: group.uncomputable };
+      const groupValues = this.data.values.filter((v) => v.group == group.currentIdx).map((v) => {
+        return { key: v.key, label: v.label, samplecount: v.samplecount };
+      });
+      customgroup.values = groupValues;
+      customset.groups.push(customgroup);
+    }
+    Object.assign(self.q, {
+      type: "custom-groupset",
+      customset
+    });
+  }
+  async initGroupDiv(group) {
+    const wrapper = group.currentIdx === 0 ? this.dom.excludedWrapper : this.dom.includedWrapper;
+    if (!group.type) group.type = "values";
+    if (!group.wrapper)
+      group.wrapper = wrapper.append("div").classed("sjpp-drag-drop-div", true).style("border", "1px solid #efefef").style("display", "block").style("padding", "10px").style("vertical-align", "top");
+    group.wrapper.on("drop", (event) => {
+      const itemData = this.draggedItem.node().__data__;
+      if (itemData.group === group.currentIdx) return;
+      group.draggables.node().appendChild(this.draggedItem.node());
+      this.draggedItem.style("transition-property", "background-color").style("transition-duration", "1s").style("background-color", "#fff2cc");
+      this.data.values.find((v) => v === itemData).group = group.currentIdx;
+      event.preventDefault();
+      event.stopPropagation();
+    }).on("dragleave", (event) => {
+      event.preventDefault();
+      event.stopPropagation();
+      group.wrapper.style("background-color", "#fff");
+    }).on("dragend", (event) => {
+      event.preventDefault();
+      event.stopPropagation();
+      group.wrapper.style("background-color", "#fff");
+    }).on("dragover", (event) => {
+      event.preventDefault();
+      event.stopPropagation();
+      group.wrapper.style(
+        "background-color",
+        group.currentIdx !== this.draggedItem.node().__data__.group ? "#cfe2f3" : "#fff"
+      );
+    }).on("dragenter", (event) => {
+      if (this.draggedItem.node().__data__.group === group.currentIdx) return;
+      event.preventDefault();
+      event.stopPropagation();
+      group.wrapper.style(
+        "background-color",
+        group.currentIdx !== this.draggedItem.node().__data__.group ? "#cfe2f3" : "#fff"
+      );
+    });
+    if (group.currentIdx === 0) {
+      group.title = group.wrapper.append("div").style("display", "inline-block").style("padding", "3px 10px").style("text-align", "left").style("font-size", ".6em").style("text-transform", "uppercase").style("color", "#999").text(group.name);
+    } else {
+      group.dragActionDiv = group.wrapper.append("div").style("display", "flex").style("align-items", "center");
+      group.input = group.dragActionDiv.append("input").attr("size", 12).attr("value", group.name).style("margin", "5px").style("margin-left", "8px").style("display", "inline-block").style("font-size", ".8em").style("width", "87%").on("keyup", () => {
+        (0, import_debounce.debounce)(this.onKeyUp(group), 1e3);
+      });
+      group.inputMessage = group.dragActionDiv.append("span").style("color", "red").style("font-size", "0.7em").text("NOT unique").style("display", "none");
+      group.destroyBtn = group.dragActionDiv.append("button").style("display", "inline-block").style("padding", "0px 4px").property("disabled", this.data.groups.length <= this.minGrpNum).text("x").on("click", async () => {
+        if (this.data.groups.length <= this.minGrpNum) return;
+        this.data.groups = this.data.groups.filter((d) => d.currentIdx != group.currentIdx);
+        await this.removeGroup(group);
+      });
+    }
+    group.draggables = group.wrapper.append("div").classed("sjpp-drag-list-div", true);
+    await this.addItems(group);
+  }
+  async addItems(group) {
+    const handler = this;
+    await group.draggables.selectAll("div").data(this.data.values.filter((d) => d.group == group.currentIdx)).enter().append("div").attr("draggable", "true").attr("class", "sjpp-drag-item").style("margin", "3px").style("cursor", "default").style("padding", "3px 10px").style("border-radius", "5px").style("color", (d) => d.samplecount == 0 ? "#777" : "black").text((d) => `${d.label}${d.samplecount !== void 0 ? ` (n=${d.samplecount})` : ""}`).style("background-color", "#eee").each(function() {
+      const itemNode = select_default(this).on("dragstart", function() {
+        itemNode.style("background-color", "#fff2cc");
+        handler.draggedItem = itemNode;
+      }).on("mouseenter", function() {
+        itemNode.style("background-color", "#fff2cc");
+      }).on("mouseleave", function() {
+        itemNode.style("background-color", "#eee");
+      });
+    });
+  }
+  async removeGroup(group) {
+    this.removedGrp = true;
+    const itemsNum = group.wrapper.selectAll(".sjpp-drag-item").nodes();
+    if (itemsNum.length === 0) {
+      group.wrapper.remove();
+    } else {
+      group.input.remove();
+      group.destroyBtn.remove();
+      group.wrapper.remove();
+      for (const v of this.data.values) {
+        if (v.group == group.currentIdx) v.group = 0;
+      }
+    }
+    await this.update();
+  }
+  async update() {
+    this.dom.actionDiv.addGroup.property("disabled", this.data.groups.length >= this.maxGrpNum);
+    for (const [i, grp] of this.data.groups.entries()) {
+      if (i === 0) continue;
+      if (grp.currentIdx != i) {
+        this.data.values.filter((v) => v.group == grp.currentIdx).forEach((v) => v.group = i);
+        this.data.filters.filter((f) => f.group == grp.currentIdx).forEach((f) => f.group = i);
+        grp.currentIdx = i;
+      }
+    }
+    this.dom.grpsWrapper.selectAll(".sjpp-drag-drop-div").data(this.data.groups).each(async (group) => {
+      if (group.currentIdx !== 0) {
+        group.input.node().value = group.name;
+        group.destroyBtn.property("disabled", this.data.groups.length <= this.minGrpNum);
+      }
+      await this.addItems(group);
+    });
+  }
+  async onKeyUp(group) {
+    if (group.name == group.input.node().value) return;
+    this.editedName = true;
+    const match = this.data.groups.filter((g) => g.name == group.input.node().value);
+    if (match.length > 0) {
+      this.dom.actionDiv.applyBtn.property("disabled", true);
+      group.inputMessage.style("display", "block");
+    } else {
+      this.dom.actionDiv.applyBtn.property("disabled", false);
+      group.inputMessage.style("display", "none");
+      this.data.groups[group.currentIdx].name = group.input.node().value.trim();
+    }
+  }
+};
+export {
+  GroupSet
+};
+//# sourceMappingURL=qualitative-N4F6NITI.js.map