@sjcrh/proteinpaint-client 2.219.1 → 2.221.0

package/dist/proteinView-K4K4SP3L.js

@@ -0,0 +1,1346 @@
+import {
+  getLog2Ratio,
+  getTileConfig,
+  launchViolinPlot,
+  makeTileGrid,
+  prepareTileData,
+  renderCoverageLine,
+  renderOverviewVolcanoCard,
+  renderPTMSummaryCard,
+  renderPlaceholderTiles,
+  renderStudyTiles
+} from "./chunk-JNZL7HKB.js";
+import "./chunk-ZX75ZAUG.js";
+import "./chunk-ILEXRHF7.js";
+import {
+  DataPointInteractions,
+  LegendCircleReference,
+  PlotBase,
+  addGeneSearchbox,
+  axisstyle,
+  make_radios,
+  shapeSelector,
+  shapes,
+  table2col,
+  to_svg
+} from "./chunk-WD7FZ5EE.js";
+import {
+  aa2gmcoord
+} from "./chunk-HJ6L54YS.js";
+import "./chunk-WXSMUSU7.js";
+import {
+  Menu
+} from "./chunk-CNFTQSNE.js";
+import "./chunk-RIHO7ZD5.js";
+import "./chunk-TVJOSRCH.js";
+import {
+  icons
+} from "./chunk-3CIL7KH7.js";
+import "./chunk-T4XPCSLP.js";
+import {
+  dofetch3
+} from "./chunk-4TJO2DGU.js";
+import "./chunk-W5J3LTYS.js";
+import "./chunk-MHWYRNGA.js";
+import "./chunk-JHLF2ZC2.js";
+import {
+  TermTypes,
+  axisBottom,
+  axisLeft,
+  getColors,
+  mclass
+} from "./chunk-WJLRU5OF.js";
+import {
+  copyMerge,
+  getCompInit
+} from "./chunk-HBNB5TRH.js";
+import "./chunk-PF4DSFDR.js";
+import {
+  linear
+} from "./chunk-4OLM3KSB.js";
+import "./chunk-PWYMHUXY.js";
+import {
+  roundValue
+} from "./chunk-TLT4YIG3.js";
+import "./chunk-5R63Q5KH.js";
+import {
+  creator_default,
+  select_default
+} from "./chunk-I6Y4O3RR.js";
+import {
+  rgb
+} from "./chunk-Q5RDQNIT.js";
+import "./chunk-HS5PO5ZQ.js";
+
+// plots/proteinView.ts
+var defaultConfig = {
+  chartType: "proteinView"
+};
+var COHORT_VOLCANO_HIT_RADIUS_PADDING_PX = 3;
+var COHORT_VOLCANO_HIT_BUFFER_PX = 2;
+var COHORT_VOLCANO_HOVER_RING_SIZE_SCALE = 1.15;
+var COHORT_VOLCANO_HOVER_RING_STROKE_PX = 1.5;
+var COHORT_VOLCANO_HOVER_MAX_COHORTS = 5;
+var ProteinView = class _ProteinView extends PlotBase {
+  static {
+    this.type = "proteinView";
+  }
+  constructor(opts, api) {
+    super(opts, api);
+    this.type = _ProteinView.type;
+    this.components = {};
+  }
+  async init() {
+    const holder = this.opts.holder.append("div").style("padding", "10px");
+    this.dom = {
+      holder,
+      body: holder.append("div"),
+      tip: new Menu({ padding: "" }),
+      header: this.opts.header
+    };
+    if (this.dom.header) this.dom.header.html("Protein View");
+  }
+  getState(appState) {
+    const config = appState.plots.find((p) => p.id === this.id);
+    if (!config) throw `No plot with id='${this.id}' found`;
+    return { config };
+  }
+  maySetSandboxHeader() {
+    if (!this.dom.header) return;
+    const term = this.state.config?.tw?.term;
+    const header = `Protein View: ${term?.name}`;
+    this.dom.header.text(header);
+  }
+  async main() {
+    const term = this.state.config?.tw?.term;
+    if (!term?.name) throw new Error("proteinView: selected protein term is missing");
+    const body = {
+      genome: this.app.opts.state.vocab.genome,
+      dslabel: this.app.opts.state.vocab.dslabel,
+      term: this.state.config.tw,
+      filter: this.state.config.filter,
+      filter0: this.state.config.filter0
+    };
+    this.maySetSandboxHeader();
+    const data = await dofetch3("termdb/proteome", { body });
+    if (data.error) throw data.error;
+    this.dom.body.selectAll("*").remove();
+    const tileData = prepareTileData(data, this);
+    renderCoverageLine(this.dom.body, tileData);
+    const grid = makeTileGrid(this.dom.body);
+    renderOverviewVolcanoCard(grid, data, this, {
+      onExpandRender: (holder) => {
+        renderCohortVolcano(holder, data, this, tileData.ptmSiteCount);
+      }
+    });
+    const { missing: missingTiles } = renderStudyTiles(grid, tileData, this);
+    const ptmDataByOrganism = /* @__PURE__ */ new Map();
+    for (const cohortData of data.cohorts || []) {
+      if (!cohortData.PTMType) continue;
+      const organism = cohortData.organism;
+      const isoform = cohortData.isoform;
+      const ptmDataByIsoform = ptmDataByOrganism.get(organism) || /* @__PURE__ */ new Map();
+      ptmDataByOrganism.set(organism, ptmDataByIsoform);
+      const existingCohorts = ptmDataByIsoform.get(isoform);
+      if (!existingCohorts) {
+        ptmDataByIsoform.set(isoform, [cohortData]);
+      } else {
+        existingCohorts.push(cohortData);
+      }
+    }
+    const sections = [];
+    for (const [organism, byIso] of ptmDataByOrganism) {
+      for (const [isoform, cohorts] of byIso) {
+        sections.push({ organism, isoform, cohorts, genomeName: cohorts[0].genomeName });
+      }
+    }
+    let allGenomes = null;
+    const baseGenome = this.app.opts.genome;
+    const getGenome = async (genomeName) => {
+      if (genomeName === baseGenome.name) return baseGenome;
+      if (!allGenomes) {
+        const result = await dofetch3("genomes");
+        allGenomes = result.genomes || {};
+        for (const g2 of Object.values(allGenomes)) {
+          if (g2.chrlookup || g2.name == baseGenome.name) continue;
+          g2.chrlookup = {};
+          for (const chr in g2.majorchr) {
+            g2.chrlookup[chr.toUpperCase()] = { name: chr, len: g2.majorchr[chr], major: true };
+          }
+          for (const chr in g2.minorchr || {}) {
+            g2.chrlookup[chr.toUpperCase()] = { name: chr, len: g2.minorchr[chr] };
+          }
+        }
+      }
+      const g = allGenomes[genomeName];
+      if (!g) throw `genome ${genomeName} not supported`;
+      return g;
+    };
+    const renderPTMSectionsInto = async (holder) => {
+      if (sections.length === 1) {
+        const s = sections[0];
+        const genome = await getGenome(s.genomeName);
+        await renderPTMLollipop(holder.append("div"), s.cohorts, this, s.isoform, genome);
+        return;
+      }
+      const keyOf = (s) => `${s.organism}
${s.isoform}`;
+      const selectedKeys = /* @__PURE__ */ new Set([keyOf(sections[0])]);
+      let compareMode = false;
+      const layoutDiv = holder.append("div").style("display", "flex").style("gap", "16px").style("margin-top", "10px").style("margin-left", "70px").style("align-items", "flex-start");
+      const sidebar = layoutDiv.append("div").style("flex", "0 0 220px").style("border", "1px solid #e5e7eb").style("border-radius", "4px").style("padding", "8px").style("font-size", ".85em").style("position", "sticky").style("top", "8px").style("margin-top", "20px").style("max-height", "85vh").style("overflow", "auto");
+      const rightPane = layoutDiv.append("div").style("flex", "1 1 auto").style("min-width", "0");
+      const sidebarHeader = sidebar.append("div").style("display", "flex").style("flex-direction", "column").style("gap", "6px").style("margin-bottom", "8px");
+      sidebarHeader.append("span").style("font-weight", "600").style("font-size", "1.5em").style("text-transform", "uppercase").text("Isoforms");
+      const modeToggle = sidebarHeader.append("div").style("display", "inline-flex").style("align-items", "center").style("gap", "6px");
+      modeToggle.append("span").style("color", "#6b7280").text("Mode:");
+      make_radios({
+        holder: modeToggle.append("div").attr("aria-label", "Isoform view mode"),
+        options: [
+          { label: "Single", value: "single", checked: true },
+          { label: "Compare", value: "compare" }
+        ],
+        styles: { display: "inline-block" },
+        callback: (value) => {
+          const asCompare = value === "compare";
+          if (asCompare === compareMode) return;
+          compareMode = asCompare;
+          if (!compareMode && selectedKeys.size > 1) {
+            const first = selectedKeys.values().next().value;
+            selectedKeys.clear();
+            selectedKeys.add(first);
+          }
+          renderSidebar();
+          void renderRight();
+        }
+      });
+      const sidebarList = sidebar.append("div");
+      const sectionsByOrganism = /* @__PURE__ */ new Map();
+      for (const s of sections) {
+        const arr = sectionsByOrganism.get(s.organism) || [];
+        arr.push(s);
+        sectionsByOrganism.set(s.organism, arr);
+      }
+      const showOrganismHeading = sectionsByOrganism.size > 1;
+      const renderSidebar = () => {
+        sidebarList.selectAll("*").remove();
+        for (const [organism, items] of sectionsByOrganism) {
+          if (showOrganismHeading) {
+            sidebarList.append("div").text(organism).style("font-weight", "600").style("color", "#374151").style("margin", "6px 0 4px 0");
+          }
+          for (const s of items) {
+            const key = keyOf(s);
+            const isSelected = selectedKeys.has(key);
+            const isSoleSelection = isSelected && selectedKeys.size === 1;
+            const toggleSelection = () => {
+              if (compareMode) {
+                if (selectedKeys.has(key)) {
+                  if (selectedKeys.size > 1) selectedKeys.delete(key);
+                  else return;
+                } else selectedKeys.add(key);
+              } else {
+                if (selectedKeys.has(key) && selectedKeys.size === 1) return;
+                selectedKeys.clear();
+                selectedKeys.add(key);
+              }
+              renderSidebar();
+              void renderRight();
+            };
+            const row = sidebarList.append("div").attr("role", compareMode ? "checkbox" : "radio").attr("aria-checked", String(isSelected)).attr("aria-label", `${s.organism} ${s.isoform}`).attr("tabindex", "0").style("display", "flex").style("align-items", "center").style("gap", "6px").style("padding", "3px 4px").style("border-radius", "3px").style("background", isSelected ? "#eff6ff" : "transparent").style("cursor", "pointer").on("click", toggleSelection).on("keydown", (event) => {
+              if (event.key === "Enter" || event.key === " ") {
+                event.preventDefault();
+                toggleSelection();
+              }
+            });
+            if (compareMode) {
+              row.append("input").attr("type", "checkbox").attr("tabindex", "-1").attr("aria-hidden", "true").property("checked", isSelected).property("disabled", isSoleSelection).style("margin", "0").style("cursor", isSoleSelection ? "not-allowed" : "pointer").on("click", (event) => {
+                event.stopPropagation();
+                toggleSelection();
+              });
+            }
+            row.append("span").text(s.isoform);
+            row.append("span").style("color", "#6b7280").style("margin-left", "auto").text(String(s.cohorts.length));
+          }
+        }
+      };
+      const renderRight = async () => {
+        rightPane.selectAll("*").remove();
+        const selected = sections.filter((s) => selectedKeys.has(keyOf(s)));
+        if (!selected.length) return;
+        const cols = rightPane.append("div").style("display", "flex").style("flex-direction", "column").style("gap", "16px");
+        for (const s of selected) {
+          const col = cols.append("div").style("min-width", "0");
+          try {
+            const genome = await getGenome(s.genomeName);
+            await renderPTMLollipop(col, s.cohorts, this, s.isoform, genome);
+          } catch (err) {
+            col.append("div").style("color", "#b91c1c").style("padding", "6px").text(`Failed to render ${s.organism} \xB7 ${s.isoform}: ${err?.message || err}`);
+          }
+        }
+      };
+      renderSidebar();
+      await renderRight();
+    };
+    if (sections.length) {
+      renderPTMSummaryCard(
+        grid,
+        (data.cohorts || []).filter((c) => c.PTMType),
+        this,
+        { onExpandRender: renderPTMSectionsInto }
+      );
+    }
+    const ptmCfg = getTileConfig(this, "ptm");
+    const placeholders = missingTiles.map((t) => ({ title: t.title }));
+    if (!sections.length && ptmCfg && ptmAssaysConfigured(this)) placeholders.push({ title: ptmCfg.title });
+    renderPlaceholderTiles(grid, placeholders);
+  }
+};
+function ptmAssaysConfigured(self) {
+  const organisms = self.app.vocabApi.termdbConfig?.queries?.proteome?.organisms || {};
+  for (const org of Object.values(organisms)) {
+    for (const assay of Object.values(org?.assays || {})) if (assay?.PTMType) return true;
+  }
+  return false;
+}
+function renderCohortVolcano(holder, data, self, ptmSiteCount = 0) {
+  const dots = [];
+  const sampleRegionById = data?.sampleRegions || {};
+  for (const cohortData of data?.cohorts || []) {
+    if (cohortData.PTMType) continue;
+    const log2fc = getLog2Ratio(cohortData.foldChange);
+    const fdr = Number(cohortData.fdr);
+    const testedN = Number(cohortData.testedN);
+    const controlN = Number(cohortData.controlN);
+    if (log2fc === null || !Number.isFinite(fdr) || fdr <= 0) continue;
+    dots.push({
+      organismName: cohortData.organism,
+      disease: cohortData.disease,
+      assayName: cohortData.assayName,
+      cohortName: cohortData.cohortName,
+      proteinAccession: cohortData.proteinAccession,
+      uniqueIdentifier: cohortData.uniqueIdentifier,
+      log2fc,
+      fdr,
+      score: -Math.log10(Math.max(fdr, 1e-300)),
+      testedN: Number.isFinite(testedN) ? testedN : 0,
+      controlN: Number.isFinite(controlN) ? controlN : 0,
+      // per-dot sample identity (case + control); each sample's region comes from the
+      // response-level sampleRegions map and is listed in the dot's tooltip
+      sampleIds: Array.isArray(cohortData.sampleIds) ? cohortData.sampleIds : []
+    });
+  }
+  const panel = holder.append("div").style("margin-bottom", "14px");
+  const header = panel.append("div").style("display", "flex").style("align-items", "center").style("gap", "6px").style("margin-bottom", "6px");
+  const downloadBtn = header.append("div").style("display", "inline-block");
+  if (ptmSiteCount) {
+    header.append("div").style("font-size", ".75em").style("color", "#6b7280").text(
+      `${ptmSiteCount} site-level PTM measurement${ptmSiteCount === 1 ? "" : "s"} excluded \u2014 see the PTM track below.`
+    );
+  }
+  if (!dots.length) {
+    downloadBtn.style("display", "none");
+    panel.append("div").style("font-size", ".85em").style("color", "#666").text("No cohorts with valid fold-change and FDR to plot.");
+    return;
+  }
+  const width = 500;
+  const height = 480;
+  const margin = { top: 20, right: 30, bottom: 60, left: 70 };
+  const innerW = width - margin.left - margin.right;
+  const innerH = height - margin.top - margin.bottom;
+  let minX = Number.POSITIVE_INFINITY;
+  let maxX = Number.NEGATIVE_INFINITY;
+  let maxY = 0;
+  let maxTestedN = 0;
+  let minTestedN = Number.POSITIVE_INFINITY;
+  for (const p of dots) {
+    minX = Math.min(minX, p.log2fc);
+    maxX = Math.max(maxX, p.log2fc);
+    maxY = Math.max(maxY, p.score);
+    maxTestedN = Math.max(maxTestedN, p.testedN);
+    if (p.testedN > 0) minTestedN = Math.min(minTestedN, p.testedN);
+  }
+  if (maxY < 1) maxY = 1;
+  if (!Number.isFinite(minTestedN)) minTestedN = 1;
+  const xSpan = Math.max(0.05, maxX - minX);
+  const xPad = Math.max(0.01, xSpan * 0.1);
+  const xMin = Math.min(0, minX - xPad);
+  const xMax = Math.max(0, maxX + xPad);
+  const yMax = maxY * 1.15;
+  const xScale = linear().domain([xMin, xMax]).range([0, innerW]);
+  const yScale = linear().domain([0, yMax]).range([innerH, 0]);
+  const radiusRange = [4, 12];
+  const radiusScale = linear().domain([minTestedN, Math.max(minTestedN + 1, maxTestedN)]).range(radiusRange);
+  let scaleDotSize = true;
+  const getDotRadius = (d) => scaleDotSize ? radiusScale(Math.max(minTestedN, d.testedN || minTestedN)) : (radiusRange[0] + radiusRange[1]) / 2;
+  const organismNames = [...new Set(dots.map((d) => d.organismName).filter(Boolean))].sort();
+  const assayNames = [...new Set(dots.map((d) => d.assayName))].sort();
+  const cohortNames = [...new Set(dots.map((d) => d.cohortName))].sort();
+  const proteinAccessions = [...new Set(dots.map((d) => d.proteinAccession))].sort();
+  const organismColorScale = getColors(organismNames.length).domain(organismNames);
+  const assayColorScale = getColors(assayNames.length).domain(assayNames);
+  const cohortColorScale = getColors(cohortNames.length).domain(cohortNames);
+  const proteinColorScale = getColors(proteinAccessions.length).domain(proteinAccessions);
+  const organismColors = new Map(
+    organismNames.map((name) => [name, rgb(organismColorScale(name)).formatHex()])
+  );
+  const assayColors = new Map(assayNames.map((name) => [name, rgb(assayColorScale(name)).formatHex()]));
+  const cohortColors = new Map(cohortNames.map((name) => [name, rgb(cohortColorScale(name)).formatHex()]));
+  const proteinColors = new Map(
+    proteinAccessions.map((acc) => [acc, rgb(proteinColorScale(acc)).formatHex()])
+  );
+  const prioritizedShapesArray = (() => {
+    const entries = Object.entries(shapes);
+    const sorted = [
+      ...entries.filter(([, s]) => s.isFilled === true),
+      ...entries.filter(([, s]) => s.isFilled === false),
+      ...entries.filter(([, s]) => !("isFilled" in s))
+    ];
+    return sorted.map(([, s]) => s.path);
+  })();
+  const makeShapeMap = (items) => new Map(items.map((item, i) => [item, i % prioritizedShapesArray.length]));
+  const organismShapes = makeShapeMap(organismNames);
+  const assayShapes = makeShapeMap(assayNames);
+  const cohortShapes = makeShapeMap(cohortNames);
+  const proteinShapes = makeShapeMap(proteinAccessions);
+  let colorMode = "assayType";
+  let shapeMode = "organism";
+  const customGroupPrefix = "__custom_group__:";
+  const makeCustomGroupKey = (name) => `${customGroupPrefix}${name}`;
+  const isCustomGroupKey = (value) => value.startsWith(customGroupPrefix);
+  const getCustomGroupNameFromKey = (value) => value.slice(customGroupPrefix.length);
+  const customShapeGroupPrefix = "__custom_shape_group__:";
+  const makeCustomShapeGroupKey = (name) => `${customShapeGroupPrefix}${name}`;
+  const isCustomShapeGroupKey = (value) => value.startsWith(customShapeGroupPrefix);
+  const getCustomShapeGroupNameFromKey = (value) => value.slice(customShapeGroupPrefix.length);
+  const customColorDomain = Array.from({ length: 64 }, (_, i) => `custom-${i}`);
+  const customColorScale = getColors(customColorDomain.length).domain(customColorDomain);
+  const colorModesWithGroups = ["organism", "assayType", "cohort", "proteinAccession"];
+  const shapeModesWithGroups = ["organism", "assayType", "cohort", "proteinAccession"];
+  const createModeMap = (factory) => ({
+    organism: factory(),
+    assayType: factory(),
+    cohort: factory(),
+    proteinAccession: factory()
+  });
+  const customGroupsByMode = createModeMap(() => /* @__PURE__ */ new Map());
+  const customGroupColorsByMode = createModeMap(() => /* @__PURE__ */ new Map());
+  const customShapeGroupsByMode = createModeMap(() => /* @__PURE__ */ new Map());
+  const customShapeIndicesByMode = createModeMap(() => /* @__PURE__ */ new Map());
+  const checkedItemsByMode = createModeMap(() => /* @__PURE__ */ new Set());
+  const checkedShapeItemsByMode = createModeMap(() => /* @__PURE__ */ new Set());
+  const groupingModeActive = /* @__PURE__ */ new Set();
+  const shapeGroupingModeActive = /* @__PURE__ */ new Set();
+  let customColorSeed = 0;
+  const getBaseColorValue = (d, mode) => {
+    switch (mode) {
+      case "organism":
+        return d.organismName;
+      case "assayType":
+        return d.assayName;
+      case "cohort":
+        return d.cohortName;
+      case "proteinAccession":
+        return d.proteinAccession;
+      default:
+        return "";
+    }
+  };
+  const getCustomGroupOfValue = (mode, value) => {
+    for (const [group, members] of customGroupsByMode[mode]) {
+      if (members.has(value)) return group;
+    }
+    return null;
+  };
+  const getCustomGroupOfDot = (d, mode) => {
+    return getCustomGroupOfValue(mode, getBaseColorValue(d, mode));
+  };
+  const getCustomShapeGroupOfValue = (mode, value) => {
+    for (const [group, members] of customShapeGroupsByMode[mode]) {
+      if (members.has(value)) return group;
+    }
+    return null;
+  };
+  const getCustomShapeGroupOfDot = (d, mode) => {
+    return getCustomShapeGroupOfValue(mode, getBaseColorValue(d, mode));
+  };
+  const getNextCustomColor = () => {
+    const color = rgb(customColorScale(customColorDomain[customColorSeed % customColorDomain.length])).formatHex();
+    customColorSeed++;
+    return color;
+  };
+  const addOrUpdateCustomGroup = (mode, name, baseValues) => {
+    if (!name || !baseValues.length) return;
+    for (const members of customGroupsByMode[mode].values()) {
+      for (const val of baseValues) members.delete(val);
+    }
+    const existing = customGroupsByMode[mode].get(name) || /* @__PURE__ */ new Set();
+    for (const val of baseValues) existing.add(val);
+    customGroupsByMode[mode].set(name, existing);
+    if (!customGroupColorsByMode[mode].has(name)) customGroupColorsByMode[mode].set(name, getNextCustomColor());
+  };
+  const removeCustomGroup = (mode, name) => {
+    customGroupsByMode[mode].delete(name);
+    customGroupColorsByMode[mode].delete(name);
+    hiddenColor[mode].delete(makeCustomGroupKey(name));
+  };
+  const addOrUpdateCustomShapeGroup = (mode, name, baseValues) => {
+    if (!name || !baseValues.length) return;
+    for (const members of customShapeGroupsByMode[mode].values()) {
+      for (const val of baseValues) members.delete(val);
+    }
+    const existing = customShapeGroupsByMode[mode].get(name) || /* @__PURE__ */ new Set();
+    for (const val of baseValues) existing.add(val);
+    customShapeGroupsByMode[mode].set(name, existing);
+    if (!customShapeIndicesByMode[mode].has(name)) {
+      const idx = customShapeIndicesByMode[mode].size % prioritizedShapesArray.length;
+      customShapeIndicesByMode[mode].set(name, idx);
+    }
+  };
+  const removeCustomShapeGroup = (mode, name) => {
+    customShapeGroupsByMode[mode].delete(name);
+    customShapeIndicesByMode[mode].delete(name);
+    hiddenShape[mode].delete(makeCustomShapeGroupKey(name));
+  };
+  const getCustomGroupItems = (mode) => {
+    return [...customGroupsByMode[mode].keys()].sort().map((name) => makeCustomGroupKey(name));
+  };
+  const getCustomShapeGroupItems = (mode) => {
+    return [...customShapeGroupsByMode[mode].keys()].sort().map((name) => makeCustomShapeGroupKey(name));
+  };
+  const getLegendItemSampleCount = (mode, item, dotsToCount = dots) => {
+    let matched;
+    if (isCustomGroupKey(item)) {
+      const groupName = getCustomGroupNameFromKey(item);
+      matched = dotsToCount.filter(
+        (d) => getCustomGroupOfValue(mode, getBaseColorValue(d, mode)) === groupName
+      );
+    } else if (isCustomShapeGroupKey(item)) {
+      const groupName = getCustomShapeGroupNameFromKey(item);
+      matched = dotsToCount.filter(
+        (d) => getCustomShapeGroupOfValue(mode, getBaseColorValue(d, mode)) === groupName
+      );
+    } else {
+      matched = dotsToCount.filter((d) => getBaseColorValue(d, mode) === item);
+    }
+    return new Set(matched.map((d) => `${d.organismName}|${d.assayName}|${d.cohortName}`)).size;
+  };
+  const getColor = (d) => {
+    const customGroup = getCustomGroupOfDot(d, colorMode);
+    switch (colorMode) {
+      case "organism":
+        if (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? "#888";
+        return organismColors.get(d.organismName) ?? "#888";
+      case "assayType":
+        if (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? "#888";
+        return assayColors.get(d.assayName) ?? "#888";
+      case "cohort":
+        if (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? "#888";
+        return cohortColors.get(d.cohortName) ?? "#888";
+      case "proteinAccession":
+        if (customGroup) return customGroupColorsByMode[colorMode].get(customGroup) ?? "#888";
+        return proteinColors.get(d.proteinAccession) ?? "#888";
+      default:
+        return "#888";
+    }
+  };
+  const getShapeIndex = (d) => {
+    const customShapeGroup = getCustomShapeGroupOfDot(d, shapeMode);
+    if (customShapeGroup) {
+      return customShapeIndicesByMode[shapeMode].get(customShapeGroup) ?? 0;
+    }
+    switch (shapeMode) {
+      case "organism":
+        return organismShapes.get(d.organismName) ?? 0;
+      case "assayType":
+        return assayShapes.get(d.assayName) ?? 0;
+      case "cohort":
+        return cohortShapes.get(d.cohortName) ?? 0;
+      case "proteinAccession":
+        return proteinShapes.get(d.proteinAccession) ?? 0;
+      default:
+        return 0;
+    }
+  };
+  const getShapePath = (d) => {
+    const index = getShapeIndex(d) % prioritizedShapesArray.length;
+    return prioritizedShapesArray[index];
+  };
+  const getShapeTransform = (d, sizeScale = 1) => {
+    const r = getDotRadius(d) * sizeScale;
+    const scale = r / 8;
+    const x = xScale(d.log2fc) - 8 * scale;
+    const y = yScale(d.score) - 8 * scale;
+    return `translate(${x},${y}) scale(${scale})`;
+  };
+  const colorGroupingModes = [
+    { key: "organism", label: "Organism" },
+    { key: "assayType", label: "Assay" },
+    { key: "cohort", label: "Sample Set" },
+    { key: "proteinAccession", label: "Isoform" }
+  ];
+  const shapeGroupingModes = [
+    { key: "organism", label: "Organism" },
+    { key: "assayType", label: "Assay" },
+    { key: "cohort", label: "Sample Set" },
+    { key: "proteinAccession", label: "Isoform" }
+  ];
+  const makeHiddenState = () => ({
+    organism: /* @__PURE__ */ new Set(),
+    assayType: /* @__PURE__ */ new Set(),
+    cohort: /* @__PURE__ */ new Set(),
+    proteinAccession: /* @__PURE__ */ new Set()
+  });
+  const hiddenColor = makeHiddenState();
+  const hiddenShape = makeHiddenState();
+  const getColorValueByMode = (d, mode) => {
+    switch (mode) {
+      case "organism":
+        return getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode)) : d.organismName;
+      case "assayType":
+        return getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode)) : d.assayName;
+      case "cohort":
+        return getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode)) : d.cohortName;
+      case "proteinAccession":
+        return getCustomGroupOfDot(d, mode) ? makeCustomGroupKey(getCustomGroupOfDot(d, mode)) : d.proteinAccession;
+      default:
+        return "";
+    }
+  };
+  const getShapeValueByMode = (d, mode) => {
+    switch (mode) {
+      case "organism":
+        return getCustomShapeGroupOfDot(d, mode) ? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode)) : d.organismName;
+      case "assayType":
+        return getCustomShapeGroupOfDot(d, mode) ? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode)) : d.assayName;
+      case "cohort":
+        return getCustomShapeGroupOfDot(d, mode) ? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode)) : d.cohortName;
+      case "proteinAccession":
+        return getCustomShapeGroupOfDot(d, mode) ? makeCustomShapeGroupKey(getCustomShapeGroupOfDot(d, mode)) : d.proteinAccession;
+      default:
+        return "";
+    }
+  };
+  const isDotHidden = (d) => {
+    const colorValue = getColorValueByMode(d, colorMode);
+    const shapeValue = getShapeValueByMode(d, shapeMode);
+    return hiddenColor[colorMode].has(colorValue) || hiddenShape[shapeMode].has(shapeValue);
+  };
+  const getDotDistancePx = (d1, d2) => {
+    const x = xScale(d1.log2fc) - xScale(d2.log2fc);
+    const y = yScale(d1.score) - yScale(d2.score);
+    return Math.sqrt(x * x + y * y);
+  };
+  const getVisibleDots = () => dots.filter((d) => !isDotHidden(d));
+  const getVisibleTestedNStats = () => {
+    const visibleDots = getVisibleDots();
+    if (!visibleDots.length) {
+      return { domainMin: 1, domainMax: 2, minLabel: 0, maxLabel: 0 };
+    }
+    let visibleMax = 0;
+    let visibleMin = Number.POSITIVE_INFINITY;
+    for (const d of visibleDots) {
+      visibleMax = Math.max(visibleMax, d.testedN);
+      if (d.testedN > 0) visibleMin = Math.min(visibleMin, d.testedN);
+    }
+    if (!Number.isFinite(visibleMin)) visibleMin = 1;
+    const domainMax = Math.max(visibleMin + 1, visibleMax);
+    return { domainMin: visibleMin, domainMax, minLabel: visibleMin, maxLabel: visibleMax || visibleMin };
+  };
+  const updateRadiusScaleForVisibleDots = () => {
+    const stats = getVisibleTestedNStats();
+    radiusScale.domain([stats.domainMin, stats.domainMax]).range(radiusRange);
+    return stats;
+  };
+  const getClusterDots = (seed) => {
+    const thresholdPx = 5;
+    return dots.filter((d) => !isDotHidden(d) && getDotDistancePx(d, seed) < thresholdPx).sort((a, b) => getDotDistancePx(a, seed) - getDotDistancePx(b, seed));
+  };
+  const buildClusterTableData = (clusterDots) => {
+    const columns = [
+      { label: "Organism" },
+      { label: "Assay" },
+      { label: "Sample Set" },
+      { label: "Isoform" },
+      { label: "log\u2082(FC)", sortable: true },
+      { label: "FDR", sortable: true }
+    ];
+    const rows = clusterDots.map((d) => [
+      { value: d.organismName || "" },
+      { value: d.assayName || "" },
+      { value: d.cohortName || "" },
+      { value: d.uniqueIdentifier || "" },
+      { value: roundValue(d.log2fc, 3) },
+      { value: d.fdr.toExponential(2) }
+    ]);
+    return { columns, rows };
+  };
+  const updateDots = () => {
+    cohortDots.attr("fill", (d) => getColor(d)).attr("stroke", (d) => getColor(d)).attr("stroke-width", 1).attr("d", (d) => getShapePath(d)).attr("transform", (d) => getShapeTransform(d)).style("opacity", (d) => isDotHidden(d) ? 0 : 1).style("pointer-events", (d) => isDotHidden(d) ? "none" : "auto");
+  };
+  const getShapeMapInUse = () => {
+    switch (shapeMode) {
+      case "organism":
+        return organismShapes;
+      case "assayType":
+        return assayShapes;
+      case "cohort":
+        return cohortShapes;
+      case "proteinAccession":
+        return proteinShapes;
+      default:
+        return assayShapes;
+    }
+  };
+  const plotAndLegend = panel.append("div").style("display", "flex").style("align-items", "flex-start").style("gap", "4px").style("flex-wrap", "wrap");
+  const svg = plotAndLegend.append("svg").attr("width", width).attr("height", height).style("display", "block").style("max-width", "100%").style("height", "auto");
+  const g = svg.append("g").attr("transform", `translate(${margin.left},${margin.top})`);
+  const xAxis = g.append("g").attr("transform", `translate(0,${innerH})`).call(axisBottom(xScale));
+  axisstyle({ axis: xAxis, color: "black", showline: true });
+  const yAxis = g.append("g").call(axisLeft(yScale));
+  axisstyle({ axis: yAxis, color: "black", showline: true });
+  const x0 = xScale(0);
+  const pThreshold = -Math.log10(0.05);
+  const thresholdY = yScale(Math.min(yMax, pThreshold));
+  g.append("line").attr("x1", x0).attr("x2", x0).attr("y1", 0).attr("y2", innerH).attr("stroke", "black").attr("stroke-dasharray", "5 4").attr("stroke-opacity", 0.4);
+  g.append("line").attr("x1", 0).attr("x2", innerW).attr("y1", thresholdY).attr("y2", thresholdY).attr("stroke", "black").attr("stroke-dasharray", "5 4").attr("stroke-opacity", 0.4);
+  g.append("text").attr("x", innerW / 2).attr("y", innerH + 44).attr("text-anchor", "middle").style("font-weight", 600).text("log2 fold change");
+  g.append("text").attr("transform", `translate(${-50},${innerH / 2}) rotate(-90)`).attr("text-anchor", "middle").style("font-weight", 600).text("-log10(FDR)");
+  const cohortDots = g.selectAll("path.cohort-dot").data(dots).enter().append("path").attr("class", "cohort-dot").attr("transform", (d) => getShapeTransform(d, 0.9)).attr("d", (d) => getShapePath(d)).attr("fill", (d) => getColor(d)).attr("fill-opacity", 0.5).attr("stroke", (d) => getColor(d)).attr("stroke-width", 1).attr("vector-effect", "non-scaling-stroke");
+  cohortDots.transition().duration(350).attr("d", (d) => getShapePath(d)).attr("transform", (d) => getShapeTransform(d, 1));
+  const hoverLayer = g.append("g").attr("class", "cohort-volcano-hover").style("pointer-events", "none");
+  const cover = g.append("rect").attr("class", "cohort-volcano-cover").attr("x", 0).attr("y", 0).attr("width", innerW).attr("height", innerH).attr("fill", "transparent").style("pointer-events", "all").style("cursor", "default");
+  updateDots();
+  const renderDotInfoTable = (d, container) => {
+    const tbl = table2col({ holder: container.append("table") });
+    tbl.addRow("Organism", d.organismName);
+    tbl.addRow("Disease", d.disease);
+    tbl.addRow("Assay", d.assayName);
+    tbl.addRow("Sample Set", d.cohortName);
+    const dotRegions = [
+      ...new Set((d.sampleIds || []).map((sid) => sampleRegionById[sid]).filter(Boolean))
+    ];
+    if (dotRegions.length) {
+      const regionNames = self.app.vocabApi.termdbConfig?.queries?.proteome?.brainRegions?.regions || {};
+      tbl.addRow(
+        "Brain Region",
+        dotRegions.sort().map((c) => regionNames[c] ? `${regionNames[c]} (${c})` : c).join(", ")
+      );
+    }
+    tbl.addRow("Protein Accession", d.proteinAccession);
+    tbl.addRow("Isoform", d.uniqueIdentifier);
+    tbl.addRow("log2 fold change", roundValue(d.log2fc, 3));
+    tbl.addRow("FDR", d.fdr.toExponential(2));
+    tbl.addRow("-log10(FDR)", roundValue(d.score, 3));
+    tbl.addRow("Case samples", d.testedN);
+    tbl.addRow("Control samples", d.controlN);
+  };
+  const interactions = new DataPointInteractions({
+    cover,
+    hoverLayer,
+    hoverTip: self.dom.tip,
+    points: dots,
+    getX: (d) => xScale(d.log2fc),
+    getY: (d) => yScale(d.score),
+    // Function form because the size-legend menu mutates radiusRange at runtime;
+    // caching this once would leave the broad-query stale after dots are enlarged.
+    hitRadius: () => radiusRange[1] + COHORT_VOLCANO_HIT_RADIUS_PADDING_PX,
+    perDotRadius: (d) => getDotRadius(d),
+    perDotBuffer: COHORT_VOLCANO_HIT_BUFFER_PX,
+    isHidden: isDotHidden,
+    getCluster: (seed) => getClusterDots(seed),
+    toHoverSpec: (d) => ({
+      path: getShapePath(d),
+      transform: getShapeTransform(d, COHORT_VOLCANO_HOVER_RING_SIZE_SCALE),
+      stroke: "black",
+      strokeWidth: COHORT_VOLCANO_HOVER_RING_STROKE_PX
+    }),
+    maxTooltipRows: COHORT_VOLCANO_HOVER_MAX_COHORTS,
+    itemNoun: "cohort",
+    renderSingleHoverTooltip: renderDotInfoTable,
+    buildMultiHitTableData: buildClusterTableData,
+    getActions: (d) => [
+      {
+        label: "Violin plot",
+        onClick: () => {
+          launchViolinPlot(self, d.organismName, d.assayName, d.cohortName, d.uniqueIdentifier);
+        }
+      }
+    ],
+    renderSingleHitInfo: renderDotInfoTable,
+    getRowKey: (d) => d.uniqueIdentifier
+  });
+  interactions.attach();
+  const legend = plotAndLegend.append("div").style("margin", "0").style("min-width", "220px").style("font-size", ".75em").style("color", "#374151");
+  function renderSizeLegend() {
+    legendSvg.selectAll("*").remove();
+    const stats = updateRadiusScaleForVisibleDots();
+    new LegendCircleReference({
+      g: legendSvg.append("g").attr("transform", "translate(12, 8)"),
+      inputMax: radiusRange[1],
+      inputMin: radiusRange[0],
+      maxLabel: stats.maxLabel,
+      maxRadius: radiusScale(stats.domainMax),
+      minLabel: stats.minLabel,
+      minRadius: radiusScale(stats.domainMin),
+      title: "",
+      menu: {
+        minMaxLabel: "pixels",
+        callback: async (obj) => {
+          radiusRange[0] = obj.min;
+          radiusRange[1] = obj.max;
+          radiusScale.range([obj.min, obj.max]);
+          updateDots();
+          renderSizeLegend();
+        }
+      }
+    });
+  }
+  const refreshAfterVisibilityChange = () => {
+    updateRadiusScaleForVisibleDots();
+    updateDots();
+    renderColorLegend();
+    renderSizeLegend();
+  };
+  const termName = self.state.config?.tw?.term?.name || "";
+  const svgName = `${termName}.cohort-volcano`;
+  const downloadVolcanoSvg = () => {
+    const plotNode = svg.node();
+    const legendNode = legend.node();
+    if (!plotNode) return;
+    const plotWidth = width;
+    const plotHeight = height;
+    const legendRect = legendNode?.getBoundingClientRect();
+    const legendWidth = Math.max(220, Math.ceil(legendRect?.width || 220));
+    const legendHeight = Math.max(plotHeight, Math.ceil(legendRect?.height || 0));
+    const gap = 14;
+    const combinedSvg = select_default(creator_default("svg").call(document.documentElement)).attr("width", plotWidth + gap + legendWidth).attr("height", legendHeight);
+    combinedSvg.append(() => plotNode.cloneNode(true));
+    combinedSvg.append("foreignObject").attr("x", plotWidth + gap).attr("y", 0).attr("width", legendWidth).attr("height", legendHeight).append(() => {
+      const clone = legendNode.cloneNode(true);
+      clone.style.margin = "0px";
+      clone.style.minWidth = "0px";
+      return clone;
+    });
+    to_svg(combinedSvg.node(), svgName, { apply_dom_styles: true });
+  };
+  icons.download(downloadBtn, { handler: downloadVolcanoSvg, title: "Download" });
+  const colorLegendDiv = legend.append("div").style("margin-bottom", "12px");
+  const shapeLegendDiv = legend.append("div").style("margin-bottom", "12px");
+  const sizeLegendRow = legend.append("div").style("display", "flex").style("flex-direction", "column").style("gap", "6px").style("margin-top", "8px");
+  sizeLegendRow.append("div").style("border-top", "1px solid #e5e7eb").style("margin", "8px 0 8px 0");
+  const sizeModeRow = sizeLegendRow.append("div").style("display", "flex").style("align-items", "center").style("gap", "4px").style("flex-wrap", "wrap");
+  const sizeToggleCheckbox = sizeModeRow.append("input").attr("type", "checkbox").attr("aria-label", "Scale dot size by case sample size").property("checked", scaleDotSize).style("cursor", "pointer").style("margin", "0").on("change", function() {
+    scaleDotSize = this.checked;
+    sizeModeText.style("opacity", scaleDotSize ? 1 : 0.4);
+    legendSvg.style("opacity", scaleDotSize ? 1 : 0.4);
+    updateDots();
+    renderSizeLegend();
+  });
+  void sizeToggleCheckbox;
+  const sizeModeText = sizeModeRow.append("span").style("display", "inline-flex").style("gap", "6px");
+  sizeModeText.append("span").text("Scale by");
+  sizeModeText.append("span").text("Case sample size").style("font-weight", "600").style("text-decoration", "underline").style("color", "#111");
+  sizeModeText.style("opacity", scaleDotSize ? 1 : 0.4);
+  const legendSvg = sizeLegendRow.append("svg").attr("width", 190).attr("height", 110).style("display", "block");
+  legendSvg.style("opacity", scaleDotSize ? 1 : 0.4);
+  function renderColorLegend() {
+    colorLegendDiv.selectAll("*").remove();
+    shapeLegendDiv.selectAll("*").remove();
+    const setCreateButtonState = (container, isActive, inputSelector, buttonSelector, hasCheckedItems) => {
+      if (!isActive) return;
+      const inputNode = container.select(inputSelector).node();
+      const createBtn = container.select(buttonSelector);
+      if (!inputNode || createBtn.empty()) return;
+      const shouldDisable = !inputNode.value.trim() || !hasCheckedItems;
+      createBtn.property("disabled", shouldDisable).style("opacity", shouldDisable ? "0.5" : "1").style("cursor", shouldDisable ? "not-allowed" : "pointer");
+    };
+    const updateColorCreateButtonState = () => {
+      setCreateButtonState(
+        colorLegendDiv,
+        groupingModeActive.has(colorMode),
+        'input[data-role="custom-group-name"]',
+        'button[data-role="create-custom-group-submit"]',
+        checkedItemsByMode[colorMode].size > 0
+      );
+    };
+    const updateShapeCreateButtonState = () => {
+      setCreateButtonState(
+        shapeLegendDiv,
+        shapeGroupingModeActive.has(shapeMode),
+        'input[data-role="custom-shape-group-name"]',
+        'button[data-role="create-custom-shape-group-submit"]',
+        checkedShapeItemsByMode[shapeMode].size > 0
+      );
+    };
+    const modeRow = colorLegendDiv.append("div").style("display", "flex").style("gap", "10px").style("margin-bottom", "6px").style("flex-wrap", "wrap");
+    modeRow.append("span").text("Color by");
+    for (const { key, label } of colorGroupingModes) {
+      modeRow.append("span").text(label).style("cursor", "pointer").style("font-weight", key === colorMode ? "600" : "400").style("text-decoration", key === colorMode ? "underline" : "none").style("color", key === colorMode ? "#111" : "#6b7280").on("click", () => {
+        groupingModeActive.delete(colorMode);
+        checkedItemsByMode[colorMode].clear();
+        colorMode = key;
+        refreshAfterVisibilityChange();
+      });
+    }
+    const makeLegendItems = (items, colorMap) => {
+      const dotsVisibleByShape = dots.filter((d) => !hiddenShape[shapeMode].has(getShapeValueByMode(d, shapeMode)));
+      const openColorMenu = (event, name, swatch) => {
+        const menu = new Menu({ padding: "0px" });
+        const div = menu.d.append("div");
+        const hidden = hiddenColor[colorMode].has(name);
+        const hiddenCount = hiddenColor[colorMode].size;
+        div.append("div").attr("class", "sja_menuoption sja_sharp_border").text(hidden ? "Show" : "Hide").on("click", () => {
+          if (hidden) hiddenColor[colorMode].delete(name);
+          else hiddenColor[colorMode].add(name);
+          refreshAfterVisibilityChange();
+          menu.hide();
+        });
+        div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Show only").on("click", () => {
+          hiddenColor[colorMode].clear();
+          for (const item of items) {
+            if (item != name) hiddenColor[colorMode].add(item);
+          }
+          refreshAfterVisibilityChange();
+          menu.hide();
+        });
+        if (hiddenCount > 1)
+          div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Show all").on("click", () => {
+            hiddenColor[colorMode].clear();
+            refreshAfterVisibilityChange();
+            menu.hide();
+          });
+        const input = div.append("div").attr("class", "sja_sharp_border").style("padding", "0px 10px").text("Color:").append("input").attr("type", "color").attr("value", colorMap.get(name) ?? "#888").on("change", () => {
+          const newColor = input.node().value;
+          if (isCustomGroupKey(name)) {
+            customGroupColorsByMode[colorMode].set(getCustomGroupNameFromKey(name), newColor);
+          } else if (!isCustomGroupKey(name)) {
+            if (colorMode == "organism") organismColors.set(name, newColor);
+            else if (colorMode == "assayType") assayColors.set(name, newColor);
+            else if (colorMode == "cohort") cohortColors.set(name, newColor);
+            else if (colorMode == "proteinAccession") proteinColors.set(name, newColor);
+          }
+          colorMap.set(name, newColor);
+          swatch.style("background", newColor);
+          updateDots();
+          menu.hide();
+        });
+        if (isCustomGroupKey(name))
+          div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Remove group").on("click", () => {
+            removeCustomGroup(colorMode, getCustomGroupNameFromKey(name));
+            refreshAfterVisibilityChange();
+            menu.hide();
+          });
+        menu.showunder(event.target);
+      };
+      for (const name of items) {
+        const hidden = hiddenColor[colorMode].has(name);
+        const isGroup = isCustomGroupKey(name);
+        const displayName = isGroup ? getCustomGroupNameFromKey(name) : name;
+        const inGroup = !isGroup ? getCustomGroupOfValue(colorMode, name) : null;
+        const sampleCount = getLegendItemSampleCount(colorMode, name, dotsVisibleByShape);
+        if (sampleCount === 0) continue;
+        const row = colorLegendDiv.append("div").style("display", "flex").style("align-items", "center").style("gap", "6px").style("margin-bottom", "3px");
+        if (!isGroup && groupingModeActive.has(colorMode)) {
+          const cb = row.append("input").attr("type", "checkbox").style("cursor", "pointer").style("flex-shrink", "0");
+          const cbNode = cb.node();
+          cbNode.checked = checkedItemsByMode[colorMode].has(name);
+          cb.on("change", () => {
+            if (cbNode.checked) checkedItemsByMode[colorMode].add(name);
+            else checkedItemsByMode[colorMode].delete(name);
+            updateColorCreateButtonState();
+          });
+        }
+        const swatch = row.append("span").style("display", "inline-block").style("width", "10px").style("height", "10px").style("border-radius", "50%").style("background", colorMap.get(name) ?? "#888").style("opacity", hidden ? 0.35 : 0.8).style("flex-shrink", "0").style("cursor", "pointer");
+        swatch.on("click", (event) => openColorMenu(event, name, swatch));
+        row.append("span").text(`${displayName}, ${sampleCount} sample set${sampleCount === 1 ? "" : "s"}`).style("text-decoration", hidden ? "line-through" : "none").style("cursor", "pointer").on("click", (event) => openColorMenu(event, name, swatch));
+        if (isGroup) {
+          const count = customGroupsByMode[colorMode].get(getCustomGroupNameFromKey(name))?.size || 0;
+          const itemLabel = colorMode === "organism" ? "organisms" : colorMode === "assayType" ? "assays" : colorMode === "cohort" ? "sample sets" : colorMode === "proteinAccession" ? "isoforms" : "items";
+          row.append("span").style("color", "#6b7280").text(`(${count} ${itemLabel})`);
+        } else if (inGroup) {
+          row.append("span").style("color", "#6b7280").style("font-style", "italic").text(`\u2192 ${inGroup}`);
+        }
+      }
+    };
+    const buildModeLegendItems = (baseItems, baseColorMap) => {
+      const visibleBaseItems = baseItems.filter((name) => !getCustomGroupOfValue(colorMode, name));
+      const mergedColorMap = /* @__PURE__ */ new Map();
+      for (const name of visibleBaseItems) mergedColorMap.set(name, baseColorMap.get(name) ?? "#888");
+      for (const name of getCustomGroupItems(colorMode)) {
+        const rawName = getCustomGroupNameFromKey(name);
+        mergedColorMap.set(name, customGroupColorsByMode[colorMode].get(rawName) ?? "#888");
+      }
+      return { items: [...visibleBaseItems, ...getCustomGroupItems(colorMode)], colorMap: mergedColorMap };
+    };
+    const renderCustomGroupControls = () => {
+      if (!colorModesWithGroups.includes(colorMode)) return;
+      if (!groupingModeActive.has(colorMode)) {
+        const createBtn = colorLegendDiv.append("button").attr("type", "button").style("font-size", "1em").style("font-weight", "400").style("margin-top", "6px").style("padding", "0").style("border", "none").style("border-radius", "0").style("background", "transparent").style("color", "#6b7280").style("box-shadow", "none").style("cursor", "pointer").style("transition", "color 120ms ease").text("+ Create custom group").on("click", () => {
+          groupingModeActive.add(colorMode);
+          renderColorLegend();
+        });
+        createBtn.on("mouseover", function() {
+          select_default(this).style("color", "#111827");
+        }).on("mouseout", function() {
+          select_default(this).style("color", "#6b7280");
+        });
+        return;
+      }
+      colorLegendDiv.append("div").style("font-size", "11px").style("color", "#6b7280").style("margin-bottom", "4px").text("Check items to include in the new group:");
+      const controls = colorLegendDiv.append("div").style("display", "flex").style("gap", "6px").style("align-items", "center").style("flex-wrap", "wrap").style("margin-top", "4px");
+      const nameInput = controls.append("input").attr("data-role", "custom-group-name").attr("type", "text").attr("placeholder", "Group name").style("font-size", "12px").style("padding", "2px 4px").style("min-width", "100px").on("input", () => updateColorCreateButtonState());
+      controls.append("button").attr("data-role", "create-custom-group-submit").attr("type", "button").style("font-size", "12px").style("padding", "2px 6px").text("Create").on("click", () => {
+        const groupName = (nameInput.node()?.value || "").trim();
+        if (!groupName || checkedItemsByMode[colorMode].size < 1) return;
+        addOrUpdateCustomGroup(colorMode, groupName, [...checkedItemsByMode[colorMode]]);
+        checkedItemsByMode[colorMode].clear();
+        groupingModeActive.delete(colorMode);
+        refreshAfterVisibilityChange();
+      });
+      updateColorCreateButtonState();
+      controls.append("button").attr("type", "button").style("font-size", "12px").style("padding", "2px 6px").text("Cancel").on("click", () => {
+        checkedItemsByMode[colorMode].clear();
+        groupingModeActive.delete(colorMode);
+        renderColorLegend();
+      });
+    };
+    if (colorMode === "organism") {
+      const { items, colorMap } = buildModeLegendItems(organismNames, organismColors);
+      makeLegendItems(items, colorMap);
+      renderCustomGroupControls();
+    } else if (colorMode === "assayType") {
+      const { items, colorMap } = buildModeLegendItems(assayNames, assayColors);
+      makeLegendItems(items, colorMap);
+      renderCustomGroupControls();
+    } else if (colorMode === "cohort") {
+      const { items, colorMap } = buildModeLegendItems(cohortNames, cohortColors);
+      makeLegendItems(items, colorMap);
+      renderCustomGroupControls();
+    } else if (colorMode === "proteinAccession") {
+      const { items, colorMap } = buildModeLegendItems(proteinAccessions, proteinColors);
+      makeLegendItems(items, colorMap);
+      renderCustomGroupControls();
+    }
+    shapeLegendDiv.append("div").style("border-top", "1px solid #e5e7eb").style("margin", "8px 0 8px 0");
+    const shapeModeRow = shapeLegendDiv.append("div").style("display", "flex").style("gap", "10px").style("margin-bottom", "6px").style("flex-wrap", "wrap");
+    shapeModeRow.append("span").text("Shape by");
+    for (const { key, label } of shapeGroupingModes) {
+      shapeModeRow.append("span").text(label).style("cursor", "pointer").style("font-weight", key === shapeMode ? "600" : "400").style("text-decoration", key === shapeMode ? "underline" : "none").style("color", key === shapeMode ? "#111" : "#6b7280").on("click", () => {
+        shapeGroupingModeActive.delete(shapeMode);
+        checkedShapeItemsByMode[shapeMode].clear();
+        shapeMode = key;
+        refreshAfterVisibilityChange();
+      });
+    }
+    const buildShapeLegendItems = (baseItems) => {
+      const visibleBaseItems = baseItems.filter((name) => !getCustomShapeGroupOfValue(shapeMode, name));
+      return { items: [...visibleBaseItems, ...getCustomShapeGroupItems(shapeMode)] };
+    };
+    const drawShapeLegend = (items, shapeMap) => {
+      const dotsVisibleByColor = dots.filter((d) => !hiddenColor[colorMode].has(getColorValueByMode(d, colorMode)));
+      const openShapeMenu = (event, name) => {
+        const menu = new Menu({ padding: "0px" });
+        const activeShapeMap = isCustomShapeGroupKey(name) ? customShapeIndicesByMode[shapeMode] : getShapeMapInUse();
+        const div = menu.d.append("div");
+        const hidden = hiddenShape[shapeMode].has(name);
+        const hiddenCount = hiddenShape[shapeMode].size;
+        div.append("div").attr("class", "sja_menuoption sja_sharp_border").text(hidden ? "Show" : "Hide").on("click", () => {
+          if (hidden) hiddenShape[shapeMode].delete(name);
+          else hiddenShape[shapeMode].add(name);
+          refreshAfterVisibilityChange();
+          menu.hide();
+        });
+        div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Show only").on("click", () => {
+          hiddenShape[shapeMode].clear();
+          for (const item of items) {
+            if (item != name) hiddenShape[shapeMode].add(item);
+          }
+          refreshAfterVisibilityChange();
+          menu.hide();
+        });
+        if (hiddenCount > 1)
+          div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Show all").on("click", () => {
+            hiddenShape[shapeMode].clear();
+            refreshAfterVisibilityChange();
+            menu.hide();
+          });
+        div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Change shape").on("click", () => {
+          div.selectAll("*").remove();
+          shapeSelector(
+            div,
+            (index) => {
+              const shapeKey = isCustomShapeGroupKey(name) ? getCustomShapeGroupNameFromKey(name) : name;
+              activeShapeMap.set(shapeKey, index);
+              updateDots();
+              renderColorLegend();
+              menu.hide();
+            },
+            prioritizedShapesArray
+          );
+        });
+        if (isCustomShapeGroupKey(name))
+          div.append("div").attr("class", "sja_menuoption sja_sharp_border").text("Remove group").on("click", () => {
+            removeCustomShapeGroup(shapeMode, getCustomShapeGroupNameFromKey(name));
+            refreshAfterVisibilityChange();
+            menu.hide();
+          });
+        menu.showunder(event.target);
+      };
+      for (const name of items) {
+        const hidden = hiddenShape[shapeMode].has(name);
+        const isGroup = isCustomShapeGroupKey(name);
+        const displayName = isGroup ? getCustomShapeGroupNameFromKey(name) : name;
+        const inGroup = !isGroup ? getCustomShapeGroupOfValue(shapeMode, name) : null;
+        const sampleCount = getLegendItemSampleCount(shapeMode, name, dotsVisibleByColor);
+        if (sampleCount === 0) continue;
+        const row = shapeLegendDiv.append("div").style("display", "flex").style("align-items", "center").style("gap", "6px").style("margin-bottom", "3px");
+        if (!isGroup && shapeGroupingModeActive.has(shapeMode)) {
+          const cb = row.append("input").attr("type", "checkbox").style("cursor", "pointer").style("flex-shrink", "0");
+          const cbNode = cb.node();
+          cbNode.checked = checkedShapeItemsByMode[shapeMode].has(name);
+          cb.on("change", () => {
+            if (cbNode.checked) checkedShapeItemsByMode[shapeMode].add(name);
+            else checkedShapeItemsByMode[shapeMode].delete(name);
+            updateShapeCreateButtonState();
+          });
+        }
+        const icon = row.append("svg").attr("width", 16).attr("height", 16).style("display", "inline-block").style("cursor", "pointer");
+        icon.append("path").attr("transform", "scale(0.8)").attr(
+          "d",
+          prioritizedShapesArray[((isGroup ? customShapeIndicesByMode[shapeMode].get(getCustomShapeGroupNameFromKey(name)) : shapeMap.get(name)) || 0) % prioritizedShapesArray.length]
+        ).attr("fill", "#4b5563").attr("fill-opacity", hidden ? 0.35 : 0.9);
+        icon.on("click", (event) => openShapeMenu(event, name));
+        row.append("span").text(`${displayName}, ${sampleCount} sample set${sampleCount === 1 ? "" : "s"}`).style("text-decoration", hidden ? "line-through" : "none").style("cursor", "pointer").on("click", (event) => openShapeMenu(event, name));
+        if (isGroup) {
+          const count = customShapeGroupsByMode[shapeMode].get(getCustomShapeGroupNameFromKey(name))?.size || 0;
+          const itemLabel = shapeMode === "organism" ? "organisms" : shapeMode === "assayType" ? "assays" : shapeMode === "cohort" ? "sample sets" : shapeMode === "proteinAccession" ? "isoforms" : "items";
+          row.append("span").style("color", "#6b7280").text(`(${count} ${itemLabel})`);
+        } else if (inGroup) {
+          row.append("span").style("color", "#6b7280").style("font-style", "italic").text(`\u2192 ${inGroup}`);
+        }
+      }
+    };
+    const renderShapeCustomGroupControls = () => {
+      if (!shapeModesWithGroups.includes(shapeMode)) return;
+      if (!shapeGroupingModeActive.has(shapeMode)) {
+        const createBtn = shapeLegendDiv.append("button").attr("type", "button").style("font-size", "1em").style("font-weight", "400").style("margin-top", "6px").style("padding", "0").style("border", "none").style("border-radius", "0").style("background", "transparent").style("color", "#6b7280").style("box-shadow", "none").style("cursor", "pointer").style("transition", "color 120ms ease").text("+ Create custom group").on("click", () => {
+          shapeGroupingModeActive.add(shapeMode);
+          renderColorLegend();
+        });
+        createBtn.on("mouseover", function() {
+          select_default(this).style("color", "#111827");
+        }).on("mouseout", function() {
+          select_default(this).style("color", "#6b7280");
+        });
+        return;
+      }
+      shapeLegendDiv.append("div").style("font-size", "11px").style("color", "#6b7280").style("margin-bottom", "4px").text("Check items to include in the new group:");
+      const controls = shapeLegendDiv.append("div").style("display", "flex").style("gap", "6px").style("align-items", "center").style("flex-wrap", "wrap").style("margin-top", "4px");
+      const nameInput = controls.append("input").attr("data-role", "custom-shape-group-name").attr("type", "text").attr("placeholder", "Group name").style("font-size", "12px").style("padding", "2px 4px").style("min-width", "100px").on("input", () => updateShapeCreateButtonState());
+      controls.append("button").attr("data-role", "create-custom-shape-group-submit").attr("type", "button").style("font-size", "12px").style("padding", "2px 6px").text("Create").on("click", () => {
+        const groupName = (nameInput.node()?.value || "").trim();
+        if (!groupName || checkedShapeItemsByMode[shapeMode].size < 1) return;
+        addOrUpdateCustomShapeGroup(shapeMode, groupName, [...checkedShapeItemsByMode[shapeMode]]);
+        checkedShapeItemsByMode[shapeMode].clear();
+        shapeGroupingModeActive.delete(shapeMode);
+        refreshAfterVisibilityChange();
+      });
+      updateShapeCreateButtonState();
+      controls.append("button").attr("type", "button").style("font-size", "12px").style("padding", "2px 6px").text("Cancel").on("click", () => {
+        checkedShapeItemsByMode[shapeMode].clear();
+        shapeGroupingModeActive.delete(shapeMode);
+        renderColorLegend();
+      });
+    };
+    if (shapeMode === "organism") {
+      const { items } = buildShapeLegendItems(organismNames);
+      drawShapeLegend(items, organismShapes);
+      renderShapeCustomGroupControls();
+    } else if (shapeMode === "assayType") {
+      const { items } = buildShapeLegendItems(assayNames);
+      drawShapeLegend(items, assayShapes);
+      renderShapeCustomGroupControls();
+    } else if (shapeMode === "cohort") {
+      const { items } = buildShapeLegendItems(cohortNames);
+      drawShapeLegend(items, cohortShapes);
+      renderShapeCustomGroupControls();
+    } else if (shapeMode === "proteinAccession") {
+      const { items } = buildShapeLegendItems(proteinAccessions);
+      drawShapeLegend(items, proteinShapes);
+      renderShapeCustomGroupControls();
+    }
+  }
+  updateRadiusScaleForVisibleDots();
+  renderColorLegend();
+  renderSizeLegend();
+}
+async function renderPTMLollipop(holder, ptmCohorts, self, isoform, genome) {
+  if (!ptmCohorts?.length) return;
+  const custom_variants = [];
+  const mergedMclassOverride = {};
+  const gm = await getGmForPTM(ptmCohorts[0].geneName, genome.name, isoform);
+  for (const ptm of ptmCohorts) {
+    if (!gm) continue;
+    const logValue = getLog2Ratio(ptm.foldChange);
+    const wholeProteomeLog2 = getLog2Ratio(ptm.proteinFoldChange);
+    const normalizedLog2 = logValue != null && wholeProteomeLog2 != null ? logValue - wholeProteomeLog2 : null;
+    const fdr = Number(ptm.fdr);
+    const testedN = Number(ptm.testedN);
+    const controlN = Number(ptm.controlN);
+    if (ptm.mclassOverride && typeof ptm.mclassOverride == "object") {
+      Object.assign(mergedMclassOverride, ptm.mclassOverride);
+    }
+    const site = parsePTMModSites(ptm.modSites);
+    if (!site) continue;
+    const pos = aa2gmcoord(site, gm);
+    if (!Number.isInteger(pos)) continue;
+    const ptmClass = Object.keys(ptm.mclassOverride || {})[0];
+    custom_variants.push({
+      chr: gm.chr,
+      pos,
+      mname: ptm.modSites,
+      class: ptmClass,
+      dt: 1,
+      logValue,
+      wholeProteomeLog2,
+      normalizedLog2,
+      fdr,
+      testedN: Number.isFinite(testedN) ? testedN : null,
+      controlN: Number.isFinite(controlN) ? controlN : null,
+      organism: ptm.organism || null,
+      assayName: ptm.assayName || null,
+      cohortName: ptm.cohortName || null,
+      proteinAccession: ptm.proteinAccession || null,
+      PTMStr: ptm.uniqueIdentifier || null,
+      htmlSections: [
+        {
+          key: "Action",
+          label: "Launch Violin Plot",
+          callback: () => launchViolinPlot(self, ptm.organism, ptm.assayName, ptm.cohortName, ptm.uniqueIdentifier)
+        }
+      ]
+    });
+  }
+  if (!custom_variants.length) return;
+  const mclassOverride = {
+    className: "PTM",
+    classes: mergedMclassOverride
+  };
+  for (const key in mclassOverride.classes) {
+    if (mclass[key]) Object.assign(mclass[key], mclassOverride.classes[key]);
+  }
+  const tk = {
+    type: "mds3",
+    name: "PTMs",
+    custom_variants,
+    skewerModes: [
+      {
+        type: "numeric",
+        byAttribute: "logValue",
+        label: "Log2FC",
+        tooltipPrintValue: (m) => {
+          const p = Number(m.fdr);
+          return [
+            { k: "Organism", v: m.organism ?? "NA" },
+            { k: "Assay", v: m.assayName ?? "NA" },
+            { k: "Sample set", v: m.cohortName ?? "NA" },
+            { k: "PTM", v: m.PTMStr ?? "NA" },
+            { k: "Log2 fold change", v: Number.isFinite(m.logValue) ? roundValue(m.logValue, 3) : "NA" },
+            {
+              k: "Whole proteome Log2 FC",
+              v: Number.isFinite(m.wholeProteomeLog2) ? roundValue(m.wholeProteomeLog2, 3) : "NA"
+            },
+            {
+              k: "Normalized Log2 FC",
+              v: Number.isFinite(m.normalizedLog2) ? roundValue(m.normalizedLog2, 3) : "NA"
+            },
+            { k: "FDR", v: Number.isFinite(p) && p > 0 ? p.toExponential(2) : "NA" },
+            { k: "Case samples", v: Number.isFinite(m.testedN) ? m.testedN : "NA" },
+            { k: "Control samples", v: Number.isFinite(m.controlN) ? m.controlN : "NA" },
+            { k: "Protein accession", v: m.proteinAccession ?? "NA" }
+          ];
+        },
+        inuse: true,
+        axisheight: 100
+      }
+    ],
+    mclassOverride
+  };
+  const arg = {
+    holder: holder.append("div"),
+    genome,
+    nobox: true,
+    tklst: [tk],
+    mclassOverride,
+    debugmode: self.app.opts.debug,
+    query: gm.isoform,
+    hide_dsHandles: true
+  };
+  const _ = await import("./block.init-YJQTJIDO.js");
+  await _.default(arg);
+}
+function parsePTMModSites(modSites) {
+  if (!modSites) return null;
+  const regex = /([A-Za-z])(\d+)/g;
+  let m;
+  while ((m = regex.exec(modSites)) !== null) {
+    const position = Number(m[2]);
+    if (!Number.isInteger(position) || position < 1) continue;
+    return position;
+  }
+  return null;
+}
+async function getGmForPTM(geneName, genomeName, isoform) {
+  if (!geneName) return null;
+  const d = await dofetch3("genelookup", {
+    body: {
+      deep: 1,
+      genome: genomeName,
+      input: geneName
+    }
+  });
+  if (d.error || !Array.isArray(d.gmlst) || !d.gmlst.length) return null;
+  const normalizedIsoform = isoform?.trim().toUpperCase();
+  const gm = d.gmlst.find((i) => i.isoform && normalizedIsoform && i.isoform.toUpperCase() == normalizedIsoform) || d.gmlst.find((i) => i.isdefault) || d.gmlst[0];
+  return gm;
+}
+async function getPlotConfig(opts) {
+  const config = structuredClone(defaultConfig);
+  if (!opts.tw) throw new Error("proteinView requires opts.tw");
+  return copyMerge(config, opts);
+}
+function makeChartBtnMenu(holder, chartsInstance) {
+  const row = holder.append("div").style("padding", "5px");
+  row.append("span").style("font-weight", "bold").text("Enter a gene name:");
+  const geneSearch = addGeneSearchbox({
+    row,
+    genome: chartsInstance.app.opts.genome,
+    tip: new Menu({ padding: "0px" }),
+    searchOnly: "gene",
+    callback: async () => {
+      if (!geneSearch.geneSymbol) throw new Error("A valid gene selection is required");
+      chartsInstance.dom.tip.hide();
+      chartsInstance.app.dispatch({
+        type: "plot_create",
+        config: {
+          chartType: "proteinView",
+          tw: {
+            term: {
+              gene: geneSearch.geneSymbol,
+              name: geneSearch.geneSymbol,
+              type: TermTypes.PROTEOME_ABUNDANCE
+            }
+          }
+        }
+      });
+    }
+  });
+}
+var proteinViewInit = getCompInit(ProteinView);
+var componentInit = proteinViewInit;
+export {
+  componentInit,
+  getPlotConfig,
+  makeChartBtnMenu,
+  proteinViewInit
+};
+//# sourceMappingURL=proteinView-K4K4SP3L.js.map