@sjcrh/proteinpaint-client 2.224.2 → 2.226.0

package/dist/chunk-XKWLP433.js

@@ -0,0 +1,328 @@
+import {
+  first_genetrack_tolist
+} from "./chunk-DPWSIN62.js";
+import {
+  HYPER_COLOR,
+  HYPO_COLOR
+} from "./chunk-6V7ITU5F.js";
+import {
+  clearsMinDeltaBeta
+} from "./chunk-2N345NXD.js";
+
+// plots/dmr/settings/defaults.ts
+function getDefaultDMRSettings(opts) {
+  const overrides = opts.settings || {};
+  const dm = opts?.app?.vocabApi?.termdbConfig?.queries?.dnaMethylation;
+  const chr = opts?.coordinateOverride?.chr;
+  const elementScale = dm?.regionAnalysis == "element" || Array.isArray(dm?.cpgChroms) && !!chr && !dm.cpgChroms.includes(chr);
+  const defaults = {
+    blockWidth: 800,
+    pad: elementScale ? 1e5 : 2e3,
+    lambda: elementScale ? 5e4 : 1e3,
+    C: 2,
+    fdr_cutoff: 0.05,
+    colors: {
+      group1: "#3b5ee6",
+      group2: "#c04e00",
+      hyper: HYPER_COLOR,
+      hypo: HYPO_COLOR
+    },
+    maxLoessRegion: 25e4,
+    minProbesForCi: 10,
+    maxRegionSize: 5e6,
+    minDeltaBeta: 0
+  };
+  if (overrides.colors) {
+    Object.assign(defaults.colors, overrides.colors);
+    delete overrides.colors;
+  }
+  return Object.assign(defaults, overrides);
+}
+
+// plots/dmr/viewModel/DmrViewModel.ts
+var CCRE_TRACK_NAME = "ENCODE cCREs";
+var MASKED_COLOR = "#aaaaaa";
+var signed = (v) => `${(v ?? 0) >= 0 ? "+" : ""}${(v ?? 0).toFixed(3)}`;
+var BELOW_FLOOR_COLOR = "#d9d9d9";
+var DmrViewModel = class {
+  constructor(dmrResult, config, genomeObj, queryChr, queryStart, queryStop) {
+    const { settings } = config;
+    const dmrBedItems = this.makeDmrBedItems(dmrResult, settings);
+    const sigCpgBedItems = this.makeSigCpgBedItems(dmrResult, settings, queryChr, queryStart, queryStop);
+    const xRange = (queryStop ?? 0) - (queryStart ?? 0);
+    const loess = dmrResult.diagnostic?.loess;
+    const showLoess = !!(loess && loess.group1_fitted.length > 0 && loess.group2_fitted.length > 0);
+    const showDots = xRange <= settings.dmr.maxLoessRegion;
+    const betaTrackResult = dmrResult.diagnostic ? this.renderBetaTrack(
+      dmrResult.diagnostic,
+      config,
+      settings.dmr.blockWidth,
+      showLoess,
+      showDots,
+      queryStart,
+      queryStop
+    ) : void 0;
+    this.viewData = {
+      tklst: this.buildTrackList(dmrBedItems, sigCpgBedItems, genomeObj, betaTrackResult?.img),
+      legendRows: this.buildLegendData(
+        config,
+        dmrResult.dmrs,
+        dmrResult.maskedDmrs || [],
+        sigCpgBedItems,
+        showLoess,
+        showDots,
+        betaTrackResult?.showCi ?? false
+      ),
+      diagnostic: dmrResult.diagnostic,
+      dmrs: dmrResult.dmrs,
+      dmrBedItems,
+      showLoess,
+      showDots,
+      notes: this.buildNotes(config, dmrResult, showDots)
+    };
+  }
+  /* Plain sentences for what the view cannot say by color alone: why a DMR is gray, and when to zoom.
+  A gray DMR with significant CpGs under it otherwise reads as a contradiction. */
+  buildNotes(config, dmrResult, showDots) {
+    const notes = [];
+    const floor = config.settings.dmr.minDeltaBeta || 0;
+    const below = dmrResult.dmrs.filter((d) => !clearsMinDeltaBeta(d.delta_beta_mean, floor));
+    if (below.length) {
+      const g1 = config.group1Name || "group 1";
+      const g2 = config.group2Name || "group 2";
+      const one = below.length == 1;
+      let text = `Light gray: ${one ? "a DMR" : `${below.length} DMRs`} that DMRcate called, but where methylation barely changes between the groups (${one ? `\u0394\u03B2 ${signed(below[0].delta_beta_mean)}` : "each"} under the volcano's minimum of ${floor}), so the volcano does not count ${one ? "it" : "them"}.`;
+      const d = config.readDepth;
+      if (d && Math.min(d.control, d.case) > 0 && Math.max(d.control, d.case) / Math.min(d.control, d.case) > 1.5) {
+        const [deep, shallow, dv, sv] = d.case > d.control ? [g2, g1, d.case, d.control] : [g1, g2, d.control, d.case];
+        text += ` In this comparison ${deep} has ${(dv / sv).toFixed(1)}\xD7 the reads per CpG of ${shallow} (${dv.toFixed(
+          2
+        )} vs ${sv.toFixed(2)}). DMRcate compares ratios of methylated to unmethylated reads, which shift with read depth, so a depth difference alone can produce a call like this, and its CpGs show as significant below.`;
+      }
+      notes.push(text);
+    }
+    const masked = dmrResult.maskedDmrs || [];
+    if (masked.length) {
+      const by = [...new Set(masked.flatMap((m) => m.maskedBy))].join(", ").toLowerCase() || "an artifact-prone region";
+      notes.push(
+        `Dark gray: ${masked.length == 1 ? "a DMR" : `${masked.length} DMRs`} in ${by}, where reads from near-identical copies of the sequence can mix and the methylation measured can be wrong, so the volcano does not count ${masked.length == 1 ? "it" : "them"}.`
+      );
+    }
+    if (!showDots) notes.push("Zoom in to see per-CpG dots.");
+    if (!config.scanChromosomes?.length)
+      notes.push(
+        "This view was saved before region views were opened from a DMR scan. Its DMRs come from DMRcate run over the whole genome at default settings, with no minimum CpG count or Min \u0394\u03B2, so they can differ from those it showed when saved. Open the region from a DMR scan to match the scan."
+      );
+    return notes;
+  }
+  buildTrackList(dmrBedItems, sigCpgBedItems, genomeObj, betaTrackImg) {
+    const tklst = [];
+    first_genetrack_tolist(genomeObj, tklst);
+    const ccre = (genomeObj?.tracks || []).find((t) => t.name == CCRE_TRACK_NAME);
+    if (ccre) tklst.push(structuredClone(ccre));
+    tklst.push({ type: "bedj", name: "DMRs", bedItems: dmrBedItems });
+    tklst.push({ type: "bedj", name: "Sig. CpGs", bedItems: sigCpgBedItems });
+    if (betaTrackImg) {
+      tklst.push({
+        type: "bigwig",
+        name: "Per-CpG Means",
+        height: 150,
+        imgData: betaTrackImg
+      });
+    }
+    return tklst;
+  }
+  buildLegendData(config, dmrs, masked, sigCpgBedItems, showLoess, showDots, showCi) {
+    const { colors } = config.settings.dmr;
+    const g1 = config.group1Name || "Group 1";
+    const g2 = config.group2Name || "Group 2";
+    const meansItems = [];
+    if (showDots) {
+      meansItems.push({ text: `${g1} (control)`, color: colors.group1 }, { text: `${g2} (case)`, color: colors.group2 });
+    }
+    if (showLoess) {
+      const ciLabel = showCi ? " + 95% CI" : "";
+      meansItems.push(
+        { text: `${g1} LOESS trend${ciLabel}`, color: colors.group1, style: showCi ? "shaded" : "dashed" },
+        { text: `${g2} LOESS trend${ciLabel}`, color: colors.group2, style: showCi ? "shaded" : "dashed" }
+      );
+    }
+    const rows = [{ label: "Per-CpG Means", items: meansItems }];
+    const floor = config.settings.dmr.minDeltaBeta || 0;
+    const counted = dmrs.filter((d) => clearsMinDeltaBeta(d.delta_beta_mean, floor));
+    const hasHyper = counted.some((d) => d.direction === "hyper");
+    const hasHypo = counted.some((d) => d.direction === "hypo");
+    const below = dmrs.length > counted.length;
+    if (hasHyper || hasHypo || below || masked.length) {
+      const items = [];
+      if (hasHyper) items.push({ text: "Hypermethylated", color: colors.hyper });
+      if (hasHypo) items.push({ text: "Hypomethylated", color: colors.hypo });
+      if (below)
+        items.push({ text: `Methylation change below ${floor}: not counted (see note)`, color: BELOW_FLOOR_COLOR });
+      if (masked.length)
+        items.push({ text: "In an artifact-prone region: not counted (see note)", color: MASKED_COLOR });
+      rows.push({ label: "DMR", items });
+    }
+    if (sigCpgBedItems.length) {
+      const items = [];
+      const hasHyperCpg = sigCpgBedItems.some((b) => b.color === colors.hyper);
+      const hasHypoCpg = sigCpgBedItems.some((b) => b.color === colors.hypo);
+      if (hasHyperCpg) items.push({ text: "Hyper (FDR sig.)", color: colors.hyper });
+      if (hasHypoCpg) items.push({ text: "Hypo (FDR sig.)", color: colors.hypo });
+      rows.push({ label: "Sig. CpGs", items });
+    }
+    return rows;
+  }
+  /**
+   * Render the per-CpG means scatter plot to an offscreen canvas and return
+   * a data URI suitable for the bigwig imgData track.
+   */
+  renderBetaTrack(diagnostic, config, blockWidth, showLoess, showDots, queryStart, queryStop) {
+    const { probes } = diagnostic;
+    if (!probes.positions.length) return void 0;
+    const { colors, minProbesForCi } = config.settings.dmr;
+    const dpr = typeof window !== "undefined" && window.devicePixelRatio > 1 ? window.devicePixelRatio : 1;
+    const width = blockWidth;
+    const height = 150;
+    const canvas = document.createElement("canvas");
+    canvas.width = width * dpr;
+    canvas.height = height * dpr;
+    const ctx = canvas.getContext("2d");
+    if (!ctx) return void 0;
+    ctx.scale(dpr, dpr);
+    const xMin = queryStart ?? probes.positions[0];
+    const xMax = queryStop ?? probes.positions[probes.positions.length - 1];
+    const xRange = xMax - xMin || 1;
+    const scaleX = (val) => (val - xMin) / xRange * width;
+    const scaleY = (val) => height - val * height;
+    ctx.clearRect(0, 0, width, height);
+    let showCi = false;
+    if (showLoess && diagnostic.loess) {
+      const { loess } = diagnostic;
+      const firstProbePos = probes.positions[0];
+      const lastProbePos = probes.positions[probes.positions.length - 1];
+      showCi = probes.positions.length >= minProbesForCi;
+      for (const [fitted, ciLower, ciUpper, color] of [
+        [loess.group1_fitted, loess.group1_ci_lower, loess.group1_ci_upper, colors.group1],
+        [loess.group2_fitted, loess.group2_ci_lower, loess.group2_ci_upper, colors.group2]
+      ]) {
+        if (!fitted.length) continue;
+        const lPos = loess.positions;
+        let iStart = 0;
+        let iEnd = lPos.length - 1;
+        while (iStart < lPos.length && lPos[iStart] < firstProbePos) iStart++;
+        while (iEnd >= 0 && lPos[iEnd] > lastProbePos) iEnd--;
+        if (iStart > iEnd) continue;
+        if (showCi) {
+          ctx.globalAlpha = 0.12;
+          ctx.fillStyle = color;
+          ctx.beginPath();
+          for (let i = iStart; i <= iEnd; i++) {
+            ctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, ciUpper[i]))));
+          }
+          for (let i = iEnd; i >= iStart; i--) {
+            ctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, ciLower[i]))));
+          }
+          ctx.closePath();
+          ctx.fill();
+        }
+        ctx.globalAlpha = 0.8;
+        ctx.strokeStyle = color;
+        ctx.lineWidth = 2;
+        ctx.setLineDash(showCi ? [] : [6, 4]);
+        ctx.beginPath();
+        for (let i = iStart; i <= iEnd; i++) {
+          ctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, fitted[i]))));
+        }
+        ctx.stroke();
+        ctx.setLineDash([]);
+      }
+    }
+    if (!showDots) {
+      ctx.globalAlpha = 1;
+      return { img: { minv: 0, maxv: 1, src: canvas.toDataURL("image/png") }, showCi };
+    }
+    for (let i = 0; i < probes.positions.length; i++) {
+      const x = scaleX(probes.positions[i]);
+      const isSig = probes.sig[i];
+      const alpha = isSig ? 0.85 : 0.3;
+      ctx.globalAlpha = alpha;
+      ctx.fillStyle = colors.group1;
+      const m1 = probes.mean_group1[i];
+      if (m1 != null) {
+        ctx.beginPath();
+        ctx.arc(x, scaleY(m1), 4, 0, Math.PI * 2);
+        ctx.fill();
+      }
+      ctx.fillStyle = colors.group2;
+      const m2 = probes.mean_group2[i];
+      if (m2 != null) {
+        ctx.beginPath();
+        ctx.arc(x, scaleY(m2), 4, 0, Math.PI * 2);
+        ctx.fill();
+      }
+    }
+    ctx.globalAlpha = 1;
+    return { img: { minv: 0, maxv: 1, src: canvas.toDataURL("image/png") }, showCi };
+  }
+  makeDmrBedItems(dmrResult, settings) {
+    const floor = settings.dmr.minDeltaBeta || 0;
+    const items = dmrResult.dmrs.map((dmr) => {
+      if (!clearsMinDeltaBeta(dmr.delta_beta_mean, floor))
+        return {
+          chr: dmr.chr,
+          start: dmr.start,
+          stop: dmr.stop,
+          color: BELOW_FLOOR_COLOR,
+          name: `\u0394\u03B2 ${signed(dmr.delta_beta_mean)}, under ${floor}: not counted`
+        };
+      const negLog = -Math.log10(Math.max(dmr.min_smoothed_fdr, 1e-300));
+      const alpha = Math.round(Math.min(255, Math.max(50, negLog / 10 * 255)));
+      const hex = alpha.toString(16).padStart(2, "0");
+      const base = dmr.direction === "hyper" ? settings.dmr.colors.hyper : settings.dmr.colors.hypo;
+      return {
+        chr: dmr.chr,
+        start: dmr.start,
+        stop: dmr.stop,
+        color: base + hex,
+        name: `\u0394\u03B2 ${signed(dmr.delta_beta_mean)}, ${dmr.no_cpgs} CpGs`
+      };
+    });
+    for (const d of dmrResult.maskedDmrs || [])
+      items.push({
+        chr: d.chr,
+        start: d.start,
+        stop: d.stop,
+        color: MASKED_COLOR,
+        name: `masked: ${d.maskedBy.join(", ").toLowerCase() || "artifact-prone region"}`
+      });
+    return items;
+  }
+  makeSigCpgBedItems(dmrResult, settings, chr, queryStart, queryStop) {
+    const diag = dmrResult.diagnostic;
+    if (!diag) return [];
+    const { probes } = diag;
+    const items = [];
+    const minDeltaBeta = 0.05;
+    for (let i = 0; i < probes.positions.length; i++) {
+      if (!probes.sig[i]) continue;
+      const pos = probes.positions[i];
+      if (queryStart != null && queryStop != null && (pos < queryStart || pos > queryStop)) continue;
+      const mg1 = probes.mean_group1[i];
+      const mg2 = probes.mean_group2[i];
+      if (mg1 == null || mg2 == null) continue;
+      const deltaBeta = mg2 - mg1;
+      if (Math.abs(deltaBeta) < minDeltaBeta) continue;
+      const color = deltaBeta >= 0 ? settings.dmr.colors.hyper : settings.dmr.colors.hypo;
+      items.push({ chr, start: pos, stop: pos + 1, color });
+    }
+    return items;
+  }
+};
+
+export {
+  getDefaultDMRSettings,
+  CCRE_TRACK_NAME,
+  DmrViewModel
+};
+//# sourceMappingURL=chunk-XKWLP433.js.map

package/dist/chunk-XKWLP433.js.map

@@ -0,0 +1,7 @@
+{
+  "version": 3,
+  "sources": ["../plots/dmr/settings/defaults.ts", "../plots/dmr/viewModel/DmrViewModel.ts"],
+  "sourcesContent": ["import type { DMRSettings } from './Settings.ts'\n\n// direction colours are shared with the server-rendered scan Manhattan\nexport { HYPER_COLOR, HYPO_COLOR } from '#shared/dmrColors.js'\nimport { HYPER_COLOR, HYPO_COLOR } from '#shared/dmrColors.js'\n\nexport function getDefaultDMRSettings(opts: any): DMRSettings {\n\tconst overrides = opts.settings || {}\n\t/* A dataset with no CpG-level matrix runs the region analysis on its element matrix, where one\n\trow is a cCRE, not a CpG. Those sit ~10kb apart against a CpG's ~100bp, so the CpG-scale window\n\tand kernel below would frame one element and smooth nothing. Scaled to element spacing instead.\n\tponytail: fixed values, not derived from the matrix's actual spacing \u2014 worth deriving only if a\n\tdataset shows up whose element density is far off this one's. The user can pan/zoom either way. */\n\tconst dm = opts?.app?.vocabApi?.termdbConfig?.queries?.dnaMethylation\n\t/* Per chromosome, not per dataset: a cohort with some shards built runs CpG resolution where one\n\texists and elements everywhere else (server resolveMethylationMatrix), so a dataset-wide flag gave\n\tthe fallback chromosomes a CpG-scale window over rows ~10 kb apart. cpgChroms is sent only for a\n\tshard-backed dataset without a genome-wide file. */\n\tconst chr = opts?.coordinateOverride?.chr\n\tconst elementScale =\n\t\tdm?.regionAnalysis == 'element' || (Array.isArray(dm?.cpgChroms) && !!chr && !dm.cpgChroms.includes(chr))\n\tconst defaults = {\n\t\tblockWidth: 800,\n\t\tpad: elementScale ? 100_000 : 2000,\n\t\tlambda: elementScale ? 50_000 : 1000,\n\t\tC: 2,\n\t\tfdr_cutoff: 0.05,\n\t\tcolors: {\n\t\t\tgroup1: '#3b5ee6',\n\t\t\tgroup2: '#c04e00',\n\t\t\thyper: HYPER_COLOR,\n\t\t\thypo: HYPO_COLOR\n\t\t},\n\t\tmaxLoessRegion: 250_000,\n\t\tminProbesForCi: 10,\n\t\tmaxRegionSize: 5_000_000,\n\t\tminDeltaBeta: 0\n\t}\n\n\t// Deep-merge colors so hyper/hypo defaults are preserved\n\t// when only group colors are overridden\n\tif (overrides.colors) {\n\t\tObject.assign(defaults.colors, overrides.colors)\n\t\tdelete overrides.colors\n\t}\n\n\treturn Object.assign(defaults, overrides)\n}\n", "import { first_genetrack_tolist } from '#common/1stGenetk'\n\n/** Name of the regulatory-element track in the genome config, if it declares one. */\nexport const CCRE_TRACK_NAME = 'ENCODE cCREs'\n/** a DMR the artifact mask dropped */\nconst MASKED_COLOR = '#aaaaaa'\n/** a delta-beta with its sign, 3 decimals */\nconst signed = (v: number | null | undefined) => `${(v ?? 0) >= 0 ? '+' : ''}${(v ?? 0).toFixed(3)}`\n/** a DMR whose |\u0394\u03B2| is under the scan's Min \u0394\u03B2 */\nconst BELOW_FLOOR_COLOR = '#d9d9d9'\nimport type { TermdbDmrSuccessResponse, DmrDiagnostic } from '#types'\nimport { clearsMinDeltaBeta } from '#types'\nimport type { DmrConfig, BedItem, LegendRow, DmrViewData } from '../DmrTypes.ts'\n\nexport class DmrViewModel {\n\tviewData: DmrViewData\n\n\tconstructor(\n\t\tdmrResult: TermdbDmrSuccessResponse,\n\t\tconfig: DmrConfig,\n\t\tgenomeObj: any,\n\t\tqueryChr: string,\n\t\tqueryStart?: number,\n\t\tqueryStop?: number\n\t) {\n\t\tconst { settings } = config\n\t\tconst dmrBedItems = this.makeDmrBedItems(dmrResult, settings)\n\t\tconst sigCpgBedItems = this.makeSigCpgBedItems(dmrResult, settings, queryChr, queryStart, queryStop)\n\n\t\tconst xRange = (queryStop ?? 0) - (queryStart ?? 0)\n\t\tconst loess = dmrResult.diagnostic?.loess\n\t\tconst showLoess = !!(loess && loess.group1_fitted.length > 0 && loess.group2_fitted.length > 0)\n\t\tconst showDots = xRange <= settings.dmr.maxLoessRegion\n\n\t\tconst betaTrackResult = dmrResult.diagnostic\n\t\t\t? this.renderBetaTrack(\n\t\t\t\t\tdmrResult.diagnostic,\n\t\t\t\t\tconfig,\n\t\t\t\t\tsettings.dmr.blockWidth,\n\t\t\t\t\tshowLoess,\n\t\t\t\t\tshowDots,\n\t\t\t\t\tqueryStart,\n\t\t\t\t\tqueryStop\n\t\t\t  )\n\t\t\t: undefined\n\n\t\tthis.viewData = {\n\t\t\ttklst: this.buildTrackList(dmrBedItems, sigCpgBedItems, genomeObj, betaTrackResult?.img),\n\t\t\tlegendRows: this.buildLegendData(\n\t\t\t\tconfig,\n\t\t\t\tdmrResult.dmrs,\n\t\t\t\tdmrResult.maskedDmrs || [],\n\t\t\t\tsigCpgBedItems,\n\t\t\t\tshowLoess,\n\t\t\t\tshowDots,\n\t\t\t\tbetaTrackResult?.showCi ?? false\n\t\t\t),\n\t\t\tdiagnostic: dmrResult.diagnostic,\n\t\t\tdmrs: dmrResult.dmrs,\n\t\t\tdmrBedItems,\n\t\t\tshowLoess,\n\t\t\tshowDots,\n\t\t\tnotes: this.buildNotes(config, dmrResult, showDots)\n\t\t}\n\t}\n\n\t/* Plain sentences for what the view cannot say by color alone: why a DMR is gray, and when to zoom.\n\tA gray DMR with significant CpGs under it otherwise reads as a contradiction. */\n\tprivate buildNotes(config: DmrConfig, dmrResult: TermdbDmrSuccessResponse, showDots: boolean): string[] {\n\t\tconst notes: string[] = []\n\t\tconst floor = config.settings.dmr.minDeltaBeta || 0\n\t\tconst below = dmrResult.dmrs.filter(d => !clearsMinDeltaBeta(d.delta_beta_mean, floor))\n\t\tif (below.length) {\n\t\t\tconst g1 = config.group1Name || 'group 1'\n\t\t\tconst g2 = config.group2Name || 'group 2'\n\t\t\tconst one = below.length == 1\n\t\t\tlet text =\n\t\t\t\t`Light gray: ${one ? 'a DMR' : `${below.length} DMRs`} that DMRcate called, but where methylation barely ` +\n\t\t\t\t`changes between the groups (${one ? `\u0394\u03B2 ${signed(below[0].delta_beta_mean)}` : 'each'} under the ` +\n\t\t\t\t`volcano's minimum of ${floor}), so the volcano does not count ${one ? 'it' : 'them'}.`\n\t\t\tconst d = config.readDepth\n\t\t\t// a group with no reads has no ratio to state\n\t\t\tif (d && Math.min(d.control, d.case) > 0 && Math.max(d.control, d.case) / Math.min(d.control, d.case) > 1.5) {\n\t\t\t\tconst [deep, shallow, dv, sv] = d.case > d.control ? [g2, g1, d.case, d.control] : [g1, g2, d.control, d.case]\n\t\t\t\ttext +=\n\t\t\t\t\t` In this comparison ${deep} has ${(dv / sv).toFixed(1)}\u00D7 the reads per CpG of ${shallow} (${dv.toFixed(\n\t\t\t\t\t\t2\n\t\t\t\t\t)} vs ` +\n\t\t\t\t\t`${sv.toFixed(2)}). DMRcate compares ratios of methylated to unmethylated reads, which shift with read ` +\n\t\t\t\t\t`depth, so a depth difference alone can produce a call like this, and its CpGs show as significant below.`\n\t\t\t}\n\t\t\tnotes.push(text)\n\t\t}\n\t\tconst masked = dmrResult.maskedDmrs || []\n\t\tif (masked.length) {\n\t\t\tconst by = [...new Set(masked.flatMap(m => m.maskedBy))].join(', ').toLowerCase() || 'an artifact-prone region'\n\t\t\tnotes.push(\n\t\t\t\t`Dark gray: ${masked.length == 1 ? 'a DMR' : `${masked.length} DMRs`} in ${by}, where reads from ` +\n\t\t\t\t\t'near-identical copies of the sequence can mix and the methylation measured can be wrong, so the volcano ' +\n\t\t\t\t\t`does not count ${masked.length == 1 ? 'it' : 'them'}.`\n\t\t\t)\n\t\t}\n\t\tif (!showDots) notes.push('Zoom in to see per-CpG dots.')\n\t\t/* A view saved before region views were opened from a scan names no scan, so the server windows the\n\t\tgenome-wide run at its defaults, which need not be the DMRs the view showed when it was saved. */\n\t\tif (!config.scanChromosomes?.length)\n\t\t\tnotes.push(\n\t\t\t\t'This view was saved before region views were opened from a DMR scan. Its DMRs come from DMRcate run over ' +\n\t\t\t\t\t'the whole genome at default settings, with no minimum CpG count or Min \u0394\u03B2, so they can differ from those ' +\n\t\t\t\t\t'it showed when saved. Open the region from a DMR scan to match the scan.'\n\t\t\t)\n\t\treturn notes\n\t}\n\n\tprivate buildTrackList(\n\t\tdmrBedItems: BedItem[],\n\t\tsigCpgBedItems: BedItem[],\n\t\tgenomeObj: any,\n\t\tbetaTrackImg?: { minv: number; maxv: number; src: string }\n\t): any[] {\n\t\tconst tklst: any[] = []\n\t\tfirst_genetrack_tolist(genomeObj, tklst)\n\t\t/* Regulatory context, switched on here rather than left in the Tracks menu. A DMR next to a\n\t\tgene model says where it is; a DMR next to the cCREs says what it is sitting on, which is the\n\t\tquestion the element-level view was answering. Taken from the genome's own declaration by\n\t\tname, so a genome that does not declare it simply renders without the row. */\n\t\tconst ccre = (genomeObj?.tracks || []).find((t: any) => t.name == CCRE_TRACK_NAME)\n\t\tif (ccre) tklst.push(structuredClone(ccre))\n\t\ttklst.push({ type: 'bedj', name: 'DMRs', bedItems: dmrBedItems })\n\t\ttklst.push({ type: 'bedj', name: 'Sig. CpGs', bedItems: sigCpgBedItems })\n\t\tif (betaTrackImg) {\n\t\t\ttklst.push({\n\t\t\t\ttype: 'bigwig',\n\t\t\t\tname: 'Per-CpG Means',\n\t\t\t\theight: 150,\n\t\t\t\timgData: betaTrackImg\n\t\t\t})\n\t\t}\n\t\treturn tklst\n\t}\n\n\tprivate buildLegendData(\n\t\tconfig: DmrConfig,\n\t\tdmrs: TermdbDmrSuccessResponse['dmrs'],\n\t\tmasked: NonNullable<TermdbDmrSuccessResponse['maskedDmrs']>,\n\t\tsigCpgBedItems: BedItem[],\n\t\tshowLoess: boolean,\n\t\tshowDots: boolean,\n\t\tshowCi: boolean\n\t): LegendRow[] {\n\t\tconst { colors } = config.settings.dmr\n\t\tconst g1 = config.group1Name || 'Group 1'\n\t\tconst g2 = config.group2Name || 'Group 2'\n\t\tconst meansItems: LegendRow['items'] = []\n\t\tif (showDots) {\n\t\t\tmeansItems.push({ text: `${g1} (control)`, color: colors.group1 }, { text: `${g2} (case)`, color: colors.group2 })\n\t\t}\n\t\tif (showLoess) {\n\t\t\tconst ciLabel = showCi ? ' + 95% CI' : ''\n\t\t\tmeansItems.push(\n\t\t\t\t{ text: `${g1} LOESS trend${ciLabel}`, color: colors.group1, style: showCi ? 'shaded' : 'dashed' },\n\t\t\t\t{ text: `${g2} LOESS trend${ciLabel}`, color: colors.group2, style: showCi ? 'shaded' : 'dashed' }\n\t\t\t)\n\t\t}\n\t\tconst rows: LegendRow[] = [{ label: 'Per-CpG Means', items: meansItems }]\n\t\t// Only show DMR legend entries for what is drawn: directions among the counted DMRs, then the gray ones\n\t\tconst floor = config.settings.dmr.minDeltaBeta || 0\n\t\tconst counted = dmrs.filter(d => clearsMinDeltaBeta(d.delta_beta_mean, floor))\n\t\tconst hasHyper = counted.some(d => d.direction === 'hyper')\n\t\tconst hasHypo = counted.some(d => d.direction === 'hypo')\n\t\tconst below = dmrs.length > counted.length\n\t\tif (hasHyper || hasHypo || below || masked.length) {\n\t\t\tconst items: LegendRow['items'] = []\n\t\t\tif (hasHyper) items.push({ text: 'Hypermethylated', color: colors.hyper })\n\t\t\tif (hasHypo) items.push({ text: 'Hypomethylated', color: colors.hypo })\n\t\t\t// short here; the note under the plot says why\n\t\t\tif (below)\n\t\t\t\titems.push({ text: `Methylation change below ${floor}: not counted (see note)`, color: BELOW_FLOOR_COLOR })\n\t\t\tif (masked.length)\n\t\t\t\titems.push({ text: 'In an artifact-prone region: not counted (see note)', color: MASKED_COLOR })\n\t\t\trows.push({ label: 'DMR', items })\n\t\t}\n\t\tif (sigCpgBedItems.length) {\n\t\t\tconst items: LegendRow['items'] = []\n\t\t\tconst hasHyperCpg = sigCpgBedItems.some(b => b.color === colors.hyper)\n\t\t\tconst hasHypoCpg = sigCpgBedItems.some(b => b.color === colors.hypo)\n\t\t\tif (hasHyperCpg) items.push({ text: 'Hyper (FDR sig.)', color: colors.hyper })\n\t\t\tif (hasHypoCpg) items.push({ text: 'Hypo (FDR sig.)', color: colors.hypo })\n\t\t\trows.push({ label: 'Sig. CpGs', items })\n\t\t}\n\t\treturn rows\n\t}\n\n\t/**\n\t * Render the per-CpG means scatter plot to an offscreen canvas and return\n\t * a data URI suitable for the bigwig imgData track.\n\t */\n\tprivate renderBetaTrack(\n\t\tdiagnostic: DmrDiagnostic,\n\t\tconfig: DmrConfig,\n\t\tblockWidth: number,\n\t\tshowLoess: boolean,\n\t\tshowDots: boolean,\n\t\tqueryStart?: number,\n\t\tqueryStop?: number\n\t): { img: { minv: number; maxv: number; src: string }; showCi: boolean } | undefined {\n\t\tconst { probes } = diagnostic\n\t\tif (!probes.positions.length) return undefined\n\n\t\tconst { colors, minProbesForCi } = config.settings.dmr\n\t\tconst dpr = typeof window !== 'undefined' && window.devicePixelRatio > 1 ? window.devicePixelRatio : 1\n\t\tconst width = blockWidth\n\t\tconst height = 150\n\n\t\tconst canvas = document.createElement('canvas')\n\t\tcanvas.width = width * dpr\n\t\tcanvas.height = height * dpr\n\t\tconst ctx = canvas.getContext('2d')\n\t\tif (!ctx) return undefined\n\t\tctx.scale(dpr, dpr)\n\n\t\t// Use the full block view range so dots align with bedj tracks above.\n\t\t// The block stretches the image to fill the view from queryStart to queryStop.\n\t\tconst xMin = queryStart ?? probes.positions[0]\n\t\tconst xMax = queryStop ?? probes.positions[probes.positions.length - 1]\n\t\tconst xRange = xMax - xMin || 1\n\t\tconst scaleX = (val: number) => ((val - xMin) / xRange) * width\n\t\tconst scaleY = (val: number) => height - val * height // beta 0-1\n\n\t\t// Transparent background so block mouse events (yellow line) show through\n\t\tctx.clearRect(0, 0, width, height)\n\n\t\t// DMR region shading omitted \u2014 already shown as a bedj track above\n\n\t\t// Draw LOESS curves with shaded CI regions, clipped to probe data range.\n\t\t// Only show CIs when there are enough probes for a reliable estimate.\n\t\tlet showCi = false\n\t\tif (showLoess && diagnostic.loess) {\n\t\t\tconst { loess } = diagnostic\n\t\t\tconst firstProbePos = probes.positions[0]\n\t\t\tconst lastProbePos = probes.positions[probes.positions.length - 1]\n\t\t\tshowCi = probes.positions.length >= minProbesForCi\n\n\t\t\tfor (const [fitted, ciLower, ciUpper, color] of [\n\t\t\t\t[loess.group1_fitted, loess.group1_ci_lower, loess.group1_ci_upper, colors.group1],\n\t\t\t\t[loess.group2_fitted, loess.group2_ci_lower, loess.group2_ci_upper, colors.group2]\n\t\t\t] as [number[], number[], number[], string][]) {\n\t\t\t\tif (!fitted.length) continue\n\t\t\t\tconst lPos = loess.positions\n\n\t\t\t\t// Find LOESS indices within the range of actual probe positions\n\t\t\t\tlet iStart = 0\n\t\t\t\tlet iEnd = lPos.length - 1\n\t\t\t\twhile (iStart < lPos.length && lPos[iStart] < firstProbePos) iStart++\n\t\t\t\twhile (iEnd >= 0 && lPos[iEnd] > lastProbePos) iEnd--\n\t\t\t\tif (iStart > iEnd) continue\n\n\t\t\t\tif (showCi) {\n\t\t\t\t\t// Draw CI as shaded region\n\t\t\t\t\tctx.globalAlpha = 0.12\n\t\t\t\t\tctx.fillStyle = color\n\t\t\t\t\tctx.beginPath()\n\t\t\t\t\tfor (let i = iStart; i <= iEnd; i++) {\n\t\t\t\t\t\tctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, ciUpper[i]))))\n\t\t\t\t\t}\n\t\t\t\t\tfor (let i = iEnd; i >= iStart; i--) {\n\t\t\t\t\t\tctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, ciLower[i]))))\n\t\t\t\t\t}\n\t\t\t\t\tctx.closePath()\n\t\t\t\t\tctx.fill()\n\t\t\t\t}\n\n\t\t\t\t// Draw LOESS fitted curve (dashed when no CI, solid otherwise)\n\t\t\t\tctx.globalAlpha = 0.8\n\t\t\t\tctx.strokeStyle = color\n\t\t\t\tctx.lineWidth = 2\n\t\t\t\tctx.setLineDash(showCi ? [] : [6, 4])\n\t\t\t\tctx.beginPath()\n\t\t\t\tfor (let i = iStart; i <= iEnd; i++) {\n\t\t\t\t\tctx.lineTo(scaleX(lPos[i]), scaleY(Math.max(0, Math.min(1, fitted[i]))))\n\t\t\t\t}\n\t\t\t\tctx.stroke()\n\t\t\t\tctx.setLineDash([])\n\t\t\t}\n\t\t}\n\n\t\t// Draw dots (hidden for large regions where only LOESS is shown)\n\t\tif (!showDots) {\n\t\t\tctx.globalAlpha = 1\n\t\t\treturn { img: { minv: 0, maxv: 1, src: canvas.toDataURL('image/png') }, showCi }\n\t\t}\n\t\tfor (let i = 0; i < probes.positions.length; i++) {\n\t\t\tconst x = scaleX(probes.positions[i])\n\t\t\tconst isSig = probes.sig[i]\n\t\t\tconst alpha = isSig ? 0.85 : 0.3\n\n\t\t\t// Group 1 (control)\n\t\t\tctx.globalAlpha = alpha\n\t\t\tctx.fillStyle = colors.group1\n\t\t\tconst m1 = probes.mean_group1[i]\n\t\t\tif (m1 != null) {\n\t\t\t\tctx.beginPath()\n\t\t\t\tctx.arc(x, scaleY(m1), 4, 0, Math.PI * 2)\n\t\t\t\tctx.fill()\n\t\t\t}\n\n\t\t\t// Group 2 (case)\n\t\t\tctx.fillStyle = colors.group2\n\t\t\tconst m2 = probes.mean_group2[i]\n\t\t\tif (m2 != null) {\n\t\t\t\tctx.beginPath()\n\t\t\t\tctx.arc(x, scaleY(m2), 4, 0, Math.PI * 2)\n\t\t\t\tctx.fill()\n\t\t\t}\n\t\t}\n\t\tctx.globalAlpha = 1\n\n\t\treturn { img: { minv: 0, maxv: 1, src: canvas.toDataURL('image/png') }, showCi }\n\t}\n\n\tprivate makeDmrBedItems(dmrResult: TermdbDmrSuccessResponse, settings: DmrConfig['settings']): BedItem[] {\n\t\tconst floor = settings.dmr.minDeltaBeta || 0\n\t\tconst items = dmrResult.dmrs.map(dmr => {\n\t\t\t// under the scan's Min \u0394\u03B2: called, but not counted by the scan\n\t\t\tif (!clearsMinDeltaBeta(dmr.delta_beta_mean, floor))\n\t\t\t\treturn {\n\t\t\t\t\tchr: dmr.chr,\n\t\t\t\t\tstart: dmr.start,\n\t\t\t\t\tstop: dmr.stop,\n\t\t\t\t\tcolor: BELOW_FLOOR_COLOR,\n\t\t\t\t\tname: `\u0394\u03B2 ${signed(dmr.delta_beta_mean)}, under ${floor}: not counted`\n\t\t\t\t}\n\t\t\t// Map -log10(min_smoothed_fdr) to alpha: more significant = more opaque\n\t\t\tconst negLog = -Math.log10(Math.max(dmr.min_smoothed_fdr, 1e-300))\n\t\t\tconst alpha = Math.round(Math.min(255, Math.max(50, (negLog / 10) * 255)))\n\t\t\tconst hex = alpha.toString(16).padStart(2, '0')\n\t\t\tconst base = dmr.direction === 'hyper' ? settings.dmr.colors.hyper : settings.dmr.colors.hypo\n\t\t\treturn {\n\t\t\t\tchr: dmr.chr,\n\t\t\t\tstart: dmr.start,\n\t\t\t\tstop: dmr.stop,\n\t\t\t\tcolor: base + hex,\n\t\t\t\tname: `\u0394\u03B2 ${signed(dmr.delta_beta_mean)}, ${dmr.no_cpgs} CpGs`\n\t\t\t}\n\t\t})\n\t\t/* DMRs the artifact mask dropped, in gray: called by DMRcate, so its significant CpGs show on\n\t\tthe Sig. CpGs track, but in a region where reads from duplicated copies can pool and beta can be\n\t\twrong, so the scan neither counts nor plots them. */\n\t\tfor (const d of dmrResult.maskedDmrs || [])\n\t\t\titems.push({\n\t\t\t\tchr: d.chr,\n\t\t\t\tstart: d.start,\n\t\t\t\tstop: d.stop,\n\t\t\t\tcolor: MASKED_COLOR,\n\t\t\t\tname: `masked: ${d.maskedBy.join(', ').toLowerCase() || 'artifact-prone region'}`\n\t\t\t})\n\t\treturn items\n\t}\n\n\tprivate makeSigCpgBedItems(\n\t\tdmrResult: TermdbDmrSuccessResponse,\n\t\tsettings: DmrConfig['settings'],\n\t\tchr: string,\n\t\tqueryStart?: number,\n\t\tqueryStop?: number\n\t): BedItem[] {\n\t\tconst diag = dmrResult.diagnostic\n\t\tif (!diag) return []\n\t\tconst { probes } = diag\n\t\tconst items: BedItem[] = []\n\t\tconst minDeltaBeta = 0.05\n\t\tfor (let i = 0; i < probes.positions.length; i++) {\n\t\t\tif (!probes.sig[i]) continue\n\t\t\tconst pos = probes.positions[i]\n\t\t\tif (queryStart != null && queryStop != null && (pos < queryStart || pos > queryStop)) continue\n\t\t\tconst mg1 = probes.mean_group1[i]\n\t\t\tconst mg2 = probes.mean_group2[i]\n\t\t\tif (mg1 == null || mg2 == null) continue\n\t\t\tconst deltaBeta = mg2 - mg1\n\t\t\tif (Math.abs(deltaBeta) < minDeltaBeta) continue\n\t\t\tconst color = deltaBeta >= 0 ? settings.dmr.colors.hyper : settings.dmr.colors.hypo\n\t\t\titems.push({ chr, start: pos, stop: pos + 1, color })\n\t\t}\n\t\treturn items\n\t}\n}\n"],
+  "mappings": 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