@sjcrh/proteinpaint-client 2.224.2 → 2.226.0

This diff represents the content of publicly available package versions that have been released to one of the supported registries. The information contained in this diff is provided for informational purposes only and reflects changes between package versions as they appear in their respective public registries.
Files changed (976) hide show
  1. package/dist/2dmaf-CSBPMYHO.js +1362 -0
  2. package/dist/AggMatrixInput-2HST4LLJ.js +402 -0
  3. package/dist/AggregateMatrix-UPOAX44L.js +37 -0
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  5. package/dist/BoxPlot-JTBQA6PL.js +1247 -0
  6. package/dist/CorrelationVolcano-AWBPVDMT.js +613 -0
  7. package/dist/Cuminc-3BXJVWIH.js +1217 -0
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  181. package/dist/dnaMethylation-FEB5GGXK.js +29 -0
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  850. /package/dist/{hierCluster-QA7HXKRD.js.map → hierCluster-XCJF5IQ6.js.map} +0 -0
  851. /package/dist/{hierCluster.config-HQ3SVKCE.js.map → hierCluster.config-E2EYOXX6.js.map} +0 -0
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  867. /package/dist/{matrix-TLMWPG7C.js.map → matrix-YBL4FZYJ.js.map} +0 -0
  868. /package/dist/{matrix.cells-IELMNYC6.js.map → matrix.cells-45ZFADK5.js.map} +0 -0
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  871. /package/dist/{matrix.groups-2REICNZK.js.map → matrix.groups-RXFXZABD.js.map} +0 -0
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  876. /package/dist/{matrix.renderers-YUSROXKN.js.map → matrix.renderers-JQTUODDS.js.map} +0 -0
  877. /package/dist/{matrix.serieses-UMAZNCMR.js.map → matrix.serieses-3IDRKSGO.js.map} +0 -0
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  879. /package/dist/{matrix.sort.unit.spec-SNB643Y6.js.map → matrix.sort.unit.spec-FOWLULHA.js.map} +0 -0
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  899. /package/dist/{profilePlot-SQ77M6LI.js.map → profilePlot-UCC4ZVHQ.js.map} +0 -0
  900. /package/dist/{proteinView-KSIZRDNP.js.map → proteinView-FBY6TK3S.js.map} +0 -0
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  902. /package/dist/{pseudobulk-H3USXM5U.js.map → pseudobulk-RUXGZ7OY.js.map} +0 -0
  903. /package/dist/{qualitative-ABXENRAF.js.map → qualitative-3AVR4GRX.js.map} +0 -0
  904. /package/dist/{qualitative-OSEJTJ4D.js.map → qualitative-5QNBKDOZ.js.map} +0 -0
  905. /package/dist/{radar2-VTDQGHWN.js.map → radar2-AOYMS54Y.js.map} +0 -0
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  908. /package/dist/{render-C3XJQ2QY.js.map → render-ASLVKYEX.js.map} +0 -0
  909. /package/dist/{report-7ZZ44X4R.js.map → report-UVYKDMQC.js.map} +0 -0
  910. /package/dist/{sampleView-CUCNI65Q.js.map → sampleView-6UHR7FSR.js.map} +0 -0
  911. /package/dist/{samplelst-S7AJQ36J.js.map → samplelst-ABC2CCNN.js.map} +0 -0
  912. /package/dist/{samplematrix-U7WM6GNB.js.map → samplematrix-36UCHZLC.js.map} +0 -0
  913. /package/dist/{sc-FMJHN2SW.js.map → sc-XLSAM725.js.map} +0 -0
  914. /package/dist/{scatter-KMAZ3ZNR.js.map → scatter-ADOBAOW2.js.map} +0 -0
  915. /package/dist/{scatter-4UMCJNEH.js.map → scatter-ZNVLI627.js.map} +0 -0
  916. /package/dist/{selectGenomeWithTklst-5SRM45BI.js.map → selectGenomeWithTklst-DPDBDYTR.js.map} +0 -0
  917. /package/dist/{singleCellCellType-GIIICJK5.js.map → singleCellCellType-STVPYZD4.js.map} +0 -0
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  919. /package/dist/{singleCellGeneExpression-2QFQHJJH.js.map → singleCellGeneExpression-PCGLU35S.js.map} +0 -0
  920. /package/dist/{singleCellGeneExpression.unit.spec-SAIETYHV.js.map → singleCellGeneExpression.unit.spec-PSLKK362.js.map} +0 -0
  921. /package/dist/{singleCellNumericValue-45H5EPIB.js.map → singleCellNumericValue-SR3SJEOB.js.map} +0 -0
  922. /package/dist/{singleCellNumericValue.unit.spec-FNKEJ2WC.js.map → singleCellNumericValue.unit.spec-PXVXJ4HJ.js.map} +0 -0
  923. /package/dist/{singleCellPlot-SP7OEGYQ.js.map → singleCellPlot-JXB7M6OH.js.map} +0 -0
  924. /package/dist/{singlecell-AVZQX4AH.js.map → singlecell-EDSX56QO.js.map} +0 -0
  925. /package/dist/{singlecell-JQKUHGIH.js.map → singlecell-PH55NFRX.js.map} +0 -0
  926. /package/dist/{snp-4SA7VABN.js.map → snp-3VEYBTAQ.js.map} +0 -0
  927. /package/dist/{snp.unit.spec-YIYGR6GW.js.map → snp.unit.spec-V7OB44US.js.map} +0 -0
  928. /package/dist/{snplocus-TDGQ57ZJ.js.map → snplocus-HX67RBT5.js.map} +0 -0
  929. /package/dist/{snplst-SWBGRYPA.js.map → snplst-H5YXCY33.js.map} +0 -0
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  931. /package/dist/{spliceevent.exonskip.diagram-PMZIQ5UG.js.map → spliceevent.exonskip.diagram-EYEL6BY6.js.map} +0 -0
  932. /package/dist/{spliceevent.noeventdiagram-A4T2PNUX.js.map → spliceevent.noeventdiagram-64OEXK7U.js.map} +0 -0
  933. /package/dist/{ssGSEA-U7D6HOIV.js.map → ssGSEA-3YWQH6KM.js.map} +0 -0
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  935. /package/dist/{stattable-DBYMPJU6.js.map → stattable-GPSBCNYC.js.map} +0 -0
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  937. /package/dist/{summarizeCnvGeneexp-YVRW7LWY.js.map → summarizeCnvGeneexp-YGI23QH5.js.map} +0 -0
  938. /package/dist/{summarizeGeneexpSurvival-ZB7IWGPS.js.map → summarizeGeneexpSurvival-KQ6OLWYR.js.map} +0 -0
  939. /package/dist/{summarizeMutationCnv-CUSYURDK.js.map → summarizeMutationCnv-XDHBNEPU.js.map} +0 -0
  940. /package/dist/{summarizeMutationDiagnosis-NSPCT5WI.js.map → summarizeMutationDiagnosis-VKIJRJ2Q.js.map} +0 -0
  941. /package/dist/{summarizeMutationSurvival-2PZZCC4G.js.map → summarizeMutationSurvival-57YKJGLE.js.map} +0 -0
  942. /package/dist/{summary-CYDZSICI.js.map → summary-4WQOVIUF.js.map} +0 -0
  943. /package/dist/{summary.integration.spec-2TLKJS3X.js.map → summary.integration.spec-FRNWBU7F.js.map} +0 -0
  944. /package/dist/{summaryInput-BRQ5JRGV.js.map → summaryInput-X7DS2YA7.js.map} +0 -0
  945. /package/dist/{sunburst-435LKL2S.js.map → sunburst-3OEAQA3O.js.map} +0 -0
  946. /package/dist/{sunburst-D5WAGHX6.js.map → sunburst-MSGTXYMM.js.map} +0 -0
  947. /package/dist/{survival-M63B6DY5.js.map → survival-5KC5CNZU.js.map} +0 -0
  948. /package/dist/{survival-MHESSYWF.js.map → survival-QXDS6N46.js.map} +0 -0
  949. /package/dist/{survival.integration.spec-WMS3FTNR.js.map → survival.integration.spec-PKENHLTZ.js.map} +0 -0
  950. /package/dist/{svgraph-LYFGVTHI.js.map → svgraph-VJLB7BBN.js.map} +0 -0
  951. /package/dist/{svmr-UR67QZIP.js.map → svmr-6BDEZAS6.js.map} +0 -0
  952. /package/dist/{swimmer-RP4SUEZS.js.map → swimmer-R3DN7N36.js.map} +0 -0
  953. /package/dist/{table-V4OOMF3B.js.map → table-YF5VORU6.js.map} +0 -0
  954. /package/dist/{termCollection-VHGVBSWW.js.map → termCollection-3KGLZFDW.js.map} +0 -0
  955. /package/dist/{termCollection-WSNM3YFK.js.map → termCollection-KSHVOPS5.js.map} +0 -0
  956. /package/dist/{termCollection.unit.spec-NCZUZL6P.js.map → termCollection.unit.spec-HTBDG5PL.js.map} +0 -0
  957. /package/dist/{termCollectionFractionSelection-XM3FJWBQ.js.map → termCollectionFractionSelection-MK4NKWUX.js.map} +0 -0
  958. /package/dist/{termCollectionFractionSelection.unit.spec-VO4SAV72.js.map → termCollectionFractionSelection.unit.spec-AMF32FDN.js.map} +0 -0
  959. /package/dist/{tk-KIELQHVI.js.map → tk-Z54DOECH.js.map} +0 -0
  960. /package/dist/{tp.ui-HAKSWLFB.js.map → tp.ui-M4TZVT53.js.map} +0 -0
  961. /package/dist/{tvs.categorical-G4DM4JY5.js.map → tvs.categorical-HY3BWCZR.js.map} +0 -0
  962. /package/dist/{tvs.condition-E5NUQONB.js.map → tvs.condition-Y36TRIX4.js.map} +0 -0
  963. /package/dist/{tvs.dt-T4BK24VZ.js.map → tvs.dt-XKVJZP7Y.js.map} +0 -0
  964. /package/dist/{tvs.dtcnv.categorical-V57TZFRA.js.map → tvs.dtcnv.categorical-OMRZR4Y7.js.map} +0 -0
  965. /package/dist/{tvs.dtcnv.continuous-D4YIB4PN.js.map → tvs.dtcnv.continuous-AGYOBI5K.js.map} +0 -0
  966. /package/dist/{tvs.dtfusion-6DUFLUNH.js.map → tvs.dtfusion-2JX5Y2IH.js.map} +0 -0
  967. /package/dist/{tvs.dtitd-GOEPAQGR.js.map → tvs.dtitd-SDSLBBWC.js.map} +0 -0
  968. /package/dist/{tvs.dtsnvindel-ASTXGC4O.js.map → tvs.dtsnvindel-LI7K464K.js.map} +0 -0
  969. /package/dist/{tvs.dtsv-7TGDEWXK.js.map → tvs.dtsv-VRCLX7QY.js.map} +0 -0
  970. /package/dist/{tvs.multivalue-SEIGL2W6.js.map → tvs.multivalue-4OTY6J2S.js.map} +0 -0
  971. /package/dist/{tvs.numeric-MLLX5L7Z.js.map → tvs.numeric-CDATYOR2.js.map} +0 -0
  972. /package/dist/{tvs.samplelst-HAV7C2EA.js.map → tvs.samplelst-76JOJG2M.js.map} +0 -0
  973. /package/dist/{tvs.survival-3B522MT2.js.map → tvs.survival-WTFJOKIZ.js.map} +0 -0
  974. /package/dist/{tvs.termCollection-R5NG4VXP.js.map → tvs.termCollection-QQXAS7PE.js.map} +0 -0
  975. /package/dist/{vocabulary-LBNHNSEN.js.map → vocabulary-6ACAEFTL.js.map} +0 -0
  976. /package/dist/{wsi.direct-ZEZO4NLR.js.map → wsi.direct-OS32TQRM.js.map} +0 -0
@@ -0,0 +1,2748 @@
1
+ import {
2
+ downloadManhattanSvg,
3
+ manhattanLayoutDefaults,
4
+ plotManhattan
5
+ } from "./chunk-RI3GAHQE.js";
6
+ import {
7
+ VolcanoModel,
8
+ getGroupColors
9
+ } from "./chunk-37ZEGLVY.js";
10
+ import {
11
+ CCRE_TRACK_NAME
12
+ } from "./chunk-XKWLP433.js";
13
+ import {
14
+ BACKGROUND_CORRECTION_TITLE,
15
+ DATermTypes,
16
+ DataPointInteractions,
17
+ GeneSetEditUI,
18
+ MultiTermWrapperEditUI,
19
+ PlotBase,
20
+ SCAN_Y_AXIS_OPTIONS,
21
+ axisstyle,
22
+ controlsInit,
23
+ downloadTable,
24
+ drawHoverShapes,
25
+ enabledTermTypes,
26
+ fileDateStamp,
27
+ fillTermWrapper,
28
+ getCombinedTermFilter,
29
+ getDNAMethTermName,
30
+ getDNAMethUnit,
31
+ getDefaultVolcanoSettings,
32
+ getGEunit,
33
+ getGroupForRegion,
34
+ getSampleNum,
35
+ onDeltaBetaAxis,
36
+ renderTable,
37
+ sayerror,
38
+ startElapsedTimer,
39
+ table2col,
40
+ to_svg,
41
+ validateVolcanoSettings,
42
+ withOthersGroup
43
+ } from "./chunk-DPWSIN62.js";
44
+ import "./chunk-HJ6L54YS.js";
45
+ import "./chunk-KZ54E2FU.js";
46
+ import {
47
+ Menu
48
+ } from "./chunk-CNFTQSNE.js";
49
+ import "./chunk-DOC3HBOV.js";
50
+ import "./chunk-TVJOSRCH.js";
51
+ import "./chunk-3CIL7KH7.js";
52
+ import "./chunk-T4XPCSLP.js";
53
+ import {
54
+ HYPER_COLOR,
55
+ HYPO_COLOR,
56
+ dofetch3
57
+ } from "./chunk-6V7ITU5F.js";
58
+ import {
59
+ uiLabel
60
+ } from "./chunk-W5J3LTYS.js";
61
+ import "./chunk-KUOXZIH4.js";
62
+ import "./chunk-T2W4JHWJ.js";
63
+ import {
64
+ DMR_SCAN_ELEMENT_TYPE,
65
+ DNA_METHYLATION,
66
+ GENE_EXPRESSION,
67
+ JUNCTION,
68
+ PROTEOME_DAP,
69
+ SINGLECELL_CELLTYPE,
70
+ axisBottom,
71
+ axisLeft,
72
+ bplen
73
+ } from "./chunk-2N345NXD.js";
74
+ import {
75
+ copyMerge,
76
+ getCompInit
77
+ } from "./chunk-HBNB5TRH.js";
78
+ import "./chunk-PF4DSFDR.js";
79
+ import {
80
+ linear
81
+ } from "./chunk-4OLM3KSB.js";
82
+ import "./chunk-PWYMHUXY.js";
83
+ import {
84
+ roundValueAuto
85
+ } from "./chunk-TLT4YIG3.js";
86
+ import "./chunk-5R63Q5KH.js";
87
+ import {
88
+ selectAll_default,
89
+ select_default
90
+ } from "./chunk-I6Y4O3RR.js";
91
+ import {
92
+ rgb
93
+ } from "./chunk-Q5RDQNIT.js";
94
+ import "./chunk-HS5PO5ZQ.js";
95
+
96
+ // plots/volcano/promoterLabel.ts
97
+ function elementNoun(elementType) {
98
+ switch (elementType) {
99
+ case void 0:
100
+ case "":
101
+ case "promoter":
102
+ return { one: "Promoter", many: "promoters" };
103
+ /* Two different promoter DEFINITIONS, deliberately given distinct nouns. 'promoter' is
104
+ the TSS -1500/+500 window (Bibikova 2011 / Sandoval 2011 -- the 450K array's
105
+ TSS1500+TSS200 categories); 'promoter_pls' is the ENCODE cCRE promoter-like element,
106
+ ~349 bp, i.e. the CpG-island core with the shores removed. They cover different numbers
107
+ of genes and their hit counts are NOT comparable, so the UI must never call both
108
+ "promoters". */
109
+ case "promoter_pls":
110
+ return { one: "cCRE promoter", many: "cCRE promoters" };
111
+ case "eqtm_block":
112
+ return { one: "eQTM block", many: "eQTM blocks" };
113
+ case "enhancer":
114
+ return { one: "Enhancer", many: "enhancers" };
115
+ /* Distal and proximal are separate ENCODE classes and separate hypotheses -- dELS are
116
+ the intronic/intergenic enhancers where myeloma hypermethylation concentrates, pELS sit
117
+ within 2 kb of a TSS and behave more promoter-like. There are 4.5x as many dELS, so their
118
+ hit counts are not comparable to each other either. Naming them apart keeps a reader from
119
+ reading two runs as the same analysis. */
120
+ case "enhancer_distal":
121
+ return { one: "Distal enhancer", many: "distal enhancers" };
122
+ case "enhancer_proximal":
123
+ return { one: "Proximal enhancer", many: "proximal enhancers" };
124
+ // de novo regions called by the genome scan, not an annotated class at all
125
+ case DMR_SCAN_ELEMENT_TYPE:
126
+ return { one: "DMR", many: "DMRs" };
127
+ default:
128
+ return { one: "Element", many: "elements" };
129
+ }
130
+ }
131
+ function formatPromoterLabel(d) {
132
+ if (!d) return "";
133
+ const id = d.promoter_id || "";
134
+ const { chr, start, stop } = d;
135
+ if (!chr || !Number.isFinite(start) || !Number.isFinite(stop)) return id;
136
+ const region = `${chr}:${start}-${stop}`;
137
+ const idx = id.match(/\.(p\d+)_[^_]*:\d+-\d+$/);
138
+ return idx ? `${idx[1]} \xB7 ${region}` : region;
139
+ }
140
+
141
+ // plots/volcano/viewModel/VolcanoViewModel.ts
142
+ function shortenGroupName(name) {
143
+ if (name.length >= 25) return name.substring(0, 20) + "...";
144
+ return name;
145
+ }
146
+ var DEPTH_RATIO_WARN = 1.5;
147
+ var VolcanoViewModel = class {
148
+ constructor(config, response, settings) {
149
+ this.numSignificant = 0;
150
+ this.numNonSignificant = 0;
151
+ /** The significant count split by direction, from the server so it reflects every
152
+ * significant row rather than the maxInteractiveDots-capped `dots`. */
153
+ this.numSignificantUp = 0;
154
+ this.numSignificantDown = 0;
155
+ this.minLogFoldChange = 0;
156
+ this.maxLogFoldChange = 0;
157
+ //Used for the y axis domain
158
+ this.minLogPValue = 0;
159
+ this.maxLogPValue = 0;
160
+ //Unpadded extents — used for the visible axis labels/ticks (only span real data)
161
+ this.minLogFoldChangeAxis = 0;
162
+ this.maxLogFoldChangeAxis = 0;
163
+ this.minLogPValueAxis = 0;
164
+ this.maxLogPValueAxis = 0;
165
+ //Dot radius in pixels (from server) — overlay rings size to match the PNG
166
+ this.dotRadiusPx = 2;
167
+ //Used in place of 0 p values that cannot be log transformed
168
+ this.minNonZeroPValue = 1e-9;
169
+ this.offset = 10;
170
+ this.bottomPad = 60;
171
+ this.horizPad = 70;
172
+ this.topPad = 40;
173
+ this.config = config;
174
+ this.response = response;
175
+ this.plotX = this.horizPad + this.offset * 2;
176
+ this.dataRows = response.data.dots;
177
+ const { caseColor, controlColor } = getGroupColors(this.config);
178
+ const barplot = { colorNegative: controlColor, colorPositive: caseColor };
179
+ this.termType = config.termType;
180
+ this.scan = response.scan;
181
+ this.singlePValue = config.termType == DATermTypes.PROTEOME_DAP || !!this.scan;
182
+ this.pValueLabel = this.setPValueLabel(settings);
183
+ this.pValueTable = {
184
+ columns: [
185
+ // a scan's effect size is delta-beta; the fold change is a difference of logits
186
+ { label: this.scan ? "\u0394\u03B2" : "log\u2082(fold-change)", barplot, sortable: true },
187
+ // DAP files carry a single FDR (adjusted p-value) and a scan a single p; other term
188
+ // types report both a raw and an adjusted p-value.
189
+ ...this.singlePValue ? [{ label: this.pValueLabel, sortable: true }] : [
190
+ { label: "Original p-value", sortable: true },
191
+ { label: "Adjusted p-value", sortable: true }
192
+ ]
193
+ ],
194
+ /** Filled in setPointData(), one row per threshold-passing dot. Populated even when the
195
+ * table is hidden — the download reads it. */
196
+ rows: [],
197
+ rowKeys: /* @__PURE__ */ new Map(),
198
+ height: settings.height + this.topPad
199
+ };
200
+ this.settings = settings;
201
+ this.dataType = this.setDataType();
202
+ this.setMinMaxValues();
203
+ const plotDim = this.setPlotDimensions();
204
+ this.setPTableColumns();
205
+ const pointData = this.setPointData(plotDim, controlColor, caseColor);
206
+ const foldChangeIdx = this.pValueTable.columns.findIndex((c) => c.barplot);
207
+ this.pValueTable.rows.sort((a, b) => b[foldChangeIdx].value - a[foldChangeIdx].value);
208
+ this.viewData = {
209
+ images: response.images || [],
210
+ termInfo: this.setTermInfo(plotDim),
211
+ plotDim,
212
+ pointData,
213
+ pValueTableData: this.pValueTable,
214
+ statsData: this.setStatsData(),
215
+ scan: this.scan,
216
+ pValueLabel: this.pValueLabel,
217
+ singlePValue: this.singlePValue,
218
+ numSignificantUp: this.numSignificantUp,
219
+ numSignificantDown: this.numSignificantDown,
220
+ xOffset: this.response.data.xOffset ?? 0,
221
+ centered: !!this.response.data.centered,
222
+ provenance: this.setProvenance(),
223
+ userActions: this.setUserActions(),
224
+ deltaBetaAxisLabel: this.setDeltaBetaAxisLabel(),
225
+ deltaPsiAxisLabel: this.setDeltaPsiAxisLabel(),
226
+ volcanoPng: response.data.volcanoPng,
227
+ plotExtent: response.data.plotExtent
228
+ };
229
+ }
230
+ /* The delta-beta axis used to read "Δβ (case − control)". Those are positional roles, not
231
+ names, so the plot showed the size of an effect but not its direction -- you had to already
232
+ know which group landed in which slot, or open a downloaded file and read the provenance line.
233
+ Name the groups instead, in subtraction order (case first), so the axis states what it plots.
234
+
235
+ Returns undefined when the group names are not available; the view falls back to the old
236
+ wording rather than rendering a broken label. */
237
+ setDeltaBetaAxisLabel() {
238
+ const groups = this.config?.samplelst?.groups;
239
+ const control = groups?.[0]?.name;
240
+ const cases = groups?.[1]?.name;
241
+ if (!control || !cases) return void 0;
242
+ const centered = this.response.data.centered ? " \u2212 median" : "";
243
+ return `\u0394\u03B2${centered} (${shortenGroupName(cases)} \u2212 ${shortenGroupName(control)})`;
244
+ }
245
+ // same as setDeltaBetaAxisLabel, for ΔPSI
246
+ setDeltaPsiAxisLabel() {
247
+ const groups = this.config?.samplelst?.groups;
248
+ const control = groups?.[0]?.name;
249
+ const cases = groups?.[1]?.name;
250
+ if (!control || !cases) return void 0;
251
+ return `\u0394PSI (${shortenGroupName(cases)} \u2212 ${shortenGroupName(control)})`;
252
+ }
253
+ /** What the y axis and the p column are called. Named here once so the axis, the table header,
254
+ * the hover rows and the multi-hit table cannot disagree. */
255
+ setPValueLabel(settings) {
256
+ if (this.termType == DATermTypes.PROTEOME_DAP) return "FDR";
257
+ if (this.scan)
258
+ return this.scan.backgroundCorrection ? "p vs matched background" : (
259
+ // a scan from before the choice existed plotted the smoothed FDR
260
+ SCAN_Y_AXIS_OPTIONS.find((o) => o.value == (this.scan.yAxis ?? "min_smoothed_fdr")).label
261
+ );
262
+ return `${settings.pValueType} p-value`;
263
+ }
264
+ setDataType() {
265
+ if (this.termType == DATermTypes.GENE_EXPRESSION) return "genes";
266
+ if (this.termType == DATermTypes.DNA_METHYLATION) return elementNoun(this.settings?.elementType).many;
267
+ if (this.termType == DATermTypes.JUNCTION) return "clusters";
268
+ if (this.termType == DATermTypes.SINGLECELL_CELLTYPE) return "genes";
269
+ if (this.termType == DATermTypes.PROTEOME_DAP) return "proteins";
270
+ if (this.termType == DATermTypes.SINGLECELL_GENE_EXPRESSION) return "cells";
271
+ throw new Error(`Unknown termType: ${this.termType}`);
272
+ }
273
+ setMinMaxValues() {
274
+ const ext = this.response.data.plotExtent;
275
+ this.minLogFoldChange = ext.xMin;
276
+ this.maxLogFoldChange = ext.xMax;
277
+ this.minLogPValue = ext.yMin;
278
+ this.maxLogPValue = ext.yMax;
279
+ this.minLogFoldChangeAxis = ext.xMinUnpadded;
280
+ this.maxLogFoldChangeAxis = ext.xMaxUnpadded;
281
+ this.minLogPValueAxis = ext.yMinUnpadded;
282
+ this.maxLogPValueAxis = ext.yMaxUnpadded;
283
+ this.dotRadiusPx = ext.dotRadiusPx;
284
+ if (ext.minNonZeroPValue > 0) this.minNonZeroPValue = ext.minNonZeroPValue;
285
+ }
286
+ setPlotDimensions() {
287
+ const ext = this.response.data.plotExtent;
288
+ const plotW = ext.pixelWidth;
289
+ const plotH = ext.pixelHeight;
290
+ const xPlotScale = linear().domain([this.minLogFoldChange, this.maxLogFoldChange]).range([0, plotW]);
291
+ const yPlotScale = linear().domain([this.minLogPValue, this.maxLogPValue]).range([plotH, 0]);
292
+ const xScale = linear().domain([this.minLogFoldChangeAxis, this.maxLogFoldChangeAxis]).range([xPlotScale(this.minLogFoldChangeAxis), xPlotScale(this.maxLogFoldChangeAxis)]);
293
+ const yScale = linear().domain([this.minLogPValueAxis, this.maxLogPValueAxis]).range([yPlotScale(this.minLogPValueAxis), yPlotScale(this.maxLogPValueAxis)]);
294
+ return {
295
+ svg: {
296
+ //20 is for the term info above the plot
297
+ height: plotH + this.topPad + this.bottomPad * 2 + this.offset * 3,
298
+ width: plotW + this.horizPad * 2
299
+ },
300
+ top: {
301
+ x: this.plotX,
302
+ y: 5
303
+ },
304
+ xAxisLabel: {
305
+ x: this.horizPad + plotW / 2 + this.offset,
306
+ y: this.topPad + plotH + this.bottomPad + this.offset
307
+ },
308
+ xScale: {
309
+ scale: xScale,
310
+ x: this.plotX,
311
+ y: plotH + this.topPad + this.offset * 2
312
+ },
313
+ yAxisLabel: {
314
+ text: `-log10(${this.pValueLabel})`,
315
+ x: this.horizPad / 3,
316
+ y: this.topPad + plotH / 2
317
+ },
318
+ yScale: {
319
+ scale: yScale,
320
+ x: this.horizPad,
321
+ y: this.topPad
322
+ },
323
+ plot: {
324
+ height: plotH,
325
+ width: plotW,
326
+ x: this.plotX,
327
+ y: this.topPad
328
+ },
329
+ logFoldChangeLine: {
330
+ x: xPlotScale(0) + this.plotX,
331
+ y1: this.topPad,
332
+ y2: plotH + this.offset * 4
333
+ },
334
+ xPlotScale,
335
+ yPlotScale
336
+ };
337
+ }
338
+ setTermInfo(plotDim) {
339
+ if (!enabledTermTypes.has(this.termType)) return;
340
+ if (this.termType == DATermTypes.PROTEOME_DAP) {
341
+ return {
342
+ y: plotDim.top.y + 10,
343
+ first: {
344
+ label: shortenGroupName(`Control (${this.response.sample_size1})`),
345
+ x: 0
346
+ },
347
+ second: {
348
+ label: shortenGroupName(`Case (${this.response.sample_size2})`),
349
+ x: this.settings.width
350
+ }
351
+ };
352
+ }
353
+ if (this.termType == DATermTypes.SINGLECELL_CELLTYPE) {
354
+ const groupLabel = `${this.config.termId} ${this.config.categoryName}`;
355
+ return {
356
+ y: plotDim.top.y + 10,
357
+ first: {
358
+ label: shortenGroupName(`Not in ${groupLabel}`),
359
+ x: 0
360
+ },
361
+ second: {
362
+ label: shortenGroupName(groupLabel),
363
+ x: this.settings.width
364
+ }
365
+ };
366
+ }
367
+ return {
368
+ //Set slightly above the plot
369
+ y: plotDim.top.y + 10,
370
+ first: {
371
+ // color: controlColor || this.settings.defaultSignColor,
372
+ label: shortenGroupName(`${this.config.samplelst.groups[0].name} (${this.response.sample_size1})`),
373
+ x: 0
374
+ // rectX: this.settings.width/2 - 10,
375
+ },
376
+ second: {
377
+ // color: caseColor || this.settings.defaultSignColor,
378
+ label: shortenGroupName(`${this.config.samplelst.groups[1].name} (${this.response.sample_size2})`),
379
+ x: this.settings.width
380
+ // rectX: this.settings.width/2 + 10,
381
+ }
382
+ };
383
+ }
384
+ setPointData(_plotDim, controlColor, caseColor) {
385
+ const radius = this.dotRadiusPx;
386
+ this.pValueTable.rows = [];
387
+ this.pValueTable.rowKeys.clear();
388
+ const dataCopy = structuredClone(this.dataRows);
389
+ for (const d of dataCopy) {
390
+ const highlightKey = this.termType === DATermTypes.DNA_METHYLATION ? d.promoter_id : this.termType === DATermTypes.JUNCTION ? d.cluster_id : d.gene_name;
391
+ d.highlighted = this.config?.highlightedData?.includes(highlightKey);
392
+ d.significant = true;
393
+ this.getGenesColor(d, d.significant, controlColor, caseColor);
394
+ if (d.significant) {
395
+ this.numSignificant++;
396
+ const row = this.singlePValue ? [
397
+ { value: roundValueAuto(this.scan ? d.delta_beta : d.fold_change) },
398
+ { value: roundValueAuto(d.original_p_value) }
399
+ ] : [
400
+ { value: roundValueAuto(d.fold_change) },
401
+ { value: roundValueAuto(d.original_p_value) },
402
+ { value: d.adjusted_p_value != void 0 ? roundValueAuto(d.adjusted_p_value) : "" }
403
+ ];
404
+ if (this.termType == DATermTypes.DNA_METHYLATION) {
405
+ if (this.scan) {
406
+ row.splice(
407
+ 1,
408
+ 0,
409
+ // fold_change carries the peak per-CpG delta-beta on a scan row
410
+ { value: roundValueAuto(d.fold_change) },
411
+ { value: d.no_cpgs },
412
+ { value: d.stop - d.start },
413
+ ...this.scan.backgroundCorrection ? [{ value: d.excess == null ? "" : roundValueAuto(d.excess) }] : []
414
+ );
415
+ } else {
416
+ row.splice(
417
+ 1,
418
+ 0,
419
+ { value: roundValueAuto(d.delta_beta) },
420
+ { value: roundValueAuto(d.mean_beta_control) },
421
+ { value: roundValueAuto(d.mean_beta_case) }
422
+ );
423
+ }
424
+ row.splice(0, 0, { value: formatPromoterLabel(d) }, { value: d.gene_name || "" });
425
+ } else if (this.termType == DATermTypes.JUNCTION) {
426
+ row[0] = { value: roundValueAuto(d.delta_psi) };
427
+ row.splice(
428
+ 1,
429
+ 0,
430
+ { value: roundValueAuto(d.psi_control) },
431
+ { value: roundValueAuto(d.psi_case) },
432
+ { value: d.n_junc }
433
+ );
434
+ row.splice(0, 0, { value: d.cluster_id }, { value: d.genes || "" });
435
+ } else if (this.termType == DATermTypes.PROTEOME_DAP) {
436
+ row.splice(0, 0, { value: d.gene_name || "" }, { value: d.gene || "" });
437
+ } else {
438
+ row.splice(0, 0, { value: d.gene_name || "" });
439
+ }
440
+ this.pValueTable.rows.push(row);
441
+ this.pValueTable.rowKeys.set(row, highlightKey);
442
+ } else {
443
+ this.numNonSignificant++;
444
+ }
445
+ d.x = d.pixel_x + this.plotX;
446
+ d.y = d.pixel_y + this.topPad;
447
+ d.radius = radius;
448
+ }
449
+ this.numSignificant = this.response.data.totalSignificantRows;
450
+ this.numNonSignificant = Math.max(0, this.response.data.totalRows - this.numSignificant);
451
+ this.numSignificantUp = this.response.data.totalSignificantUp ?? 0;
452
+ this.numSignificantDown = this.response.data.totalSignificantDown ?? 0;
453
+ dataCopy.sort((a, b) => a.highlighted - b.highlighted);
454
+ return dataCopy;
455
+ }
456
+ getGenesColor(d, significant, controlColor, caseColor) {
457
+ if (!d.gene_name && this.termType != DATermTypes.DNA_METHYLATION && this.termType != DATermTypes.JUNCTION)
458
+ throw new Error(`Missing gene_name in data: ${JSON.stringify(d)}`);
459
+ if (significant) {
460
+ const x = this.termType == DATermTypes.JUNCTION ? d.delta_psi : onDeltaBetaAxis(this.termType, this.settings) ? d.delta_beta - (this.response.data.xOffset ?? 0) : d.fold_change;
461
+ if (controlColor && caseColor) d.color = x > 0 ? caseColor : controlColor;
462
+ else d.color = this.settings.defaultSignColor;
463
+ } else d.color = this.settings.defaultNonSignColor;
464
+ }
465
+ /** One line describing what produced this result: which groups, how many samples actually
466
+ * entered the model, and every setting that changes the numbers.
467
+ *
468
+ * This exists because an exported table is the artifact that outlives the session. Re-running
469
+ * a contrast months later and getting different counts is impossible to diagnose when the
470
+ * original run's group sizes and options were never written down anywhere -- the file, the
471
+ * screenshot and the memory of it all look identical regardless of how it was configured.
472
+ * Only settings that can change the result are listed; cosmetic ones are deliberately left
473
+ * out so the line stays readable and a difference in it always means a real difference. */
474
+ setProvenance() {
475
+ const s = this.settings;
476
+ const parts = [];
477
+ if (this.config.samplelst?.groups?.length == 2) {
478
+ const [g1, g2] = this.config.samplelst.groups;
479
+ parts.push(`group1 (control) "${g1.name}" n=${this.response.sample_size1}`);
480
+ parts.push(`group2 (case) "${g2.name}" n=${this.response.sample_size2}`);
481
+ }
482
+ const conf = this.config.confounderTws?.map((t) => t?.term?.name || t?.term?.id).filter(Boolean);
483
+ parts.push(`confounders: ${conf?.length ? conf.join(" + ") : "none"}`);
484
+ if (this.termType == DATermTypes.DNA_METHYLATION) {
485
+ parts.push(`element class: ${s.elementType || "promoter"}`);
486
+ parts.push(`x axis: ${onDeltaBetaAxis(this.termType, s) ? "delta-beta" : "log2(fold-change)"}`);
487
+ const off = this.response.data.xOffset ?? 0;
488
+ if (this.response.data.centered)
489
+ parts.push(`centered on median delta-beta ${off > 0 ? "+" : ""}${roundValueAuto(off)}`);
490
+ if (this.scan) {
491
+ parts.push(`scan: ${s.scanChromosome || "whole genome"}`);
492
+ parts.push(`background correction: ${s.backgroundCorrection ? "yes" : "no"}`);
493
+ parts.push(`min CpGs per DMR: ${s.minCpgs}`);
494
+ } else parts.push(`min samples per group: ${s.minSamplesPerGroup}`);
495
+ parts.push(`exclude sex chromosomes: ${s.excludeSexChr ? "yes" : "no"}`);
496
+ } else if (this.termType == DATermTypes.GENE_EXPRESSION) {
497
+ parts.push(`method: ${s.method}`);
498
+ } else if (this.termType == DATermTypes.JUNCTION) {
499
+ parts.push(`method: ${this.response.method || s.method}`);
500
+ parts.push(`min samples per intron: ${s.minSamplesPerIntron}; min samples per group: ${s.minSamplesPerGroup}`);
501
+ parts.push(`min counts per cluster: ${s.minCountsPerCluster}`);
502
+ }
503
+ const onDeltaBeta = onDeltaBetaAxis(this.termType, s);
504
+ const effect = this.termType == DATermTypes.JUNCTION ? `|delta-PSI| > ${s.deltaPsiCutoff}` : onDeltaBeta ? `|delta-beta| > ${s.deltaBetaCutoff}` : `|log2(fold-change)| > ${s.foldChangeCutoff}`;
505
+ parts.push(`significance: ${s.pValueType} p < ${roundValueAuto(Math.pow(10, -s.pValue))}, ${effect}`);
506
+ return parts.join("; ");
507
+ }
508
+ setStatsData() {
509
+ const tableRows = [
510
+ {
511
+ label: `Percentage of significant ${this.dataType}`,
512
+ value: roundValueAuto(this.numSignificant * 100 / (this.numSignificant + this.numNonSignificant))
513
+ },
514
+ {
515
+ label: `Number of significant ${this.dataType}`,
516
+ value: this.numSignificant
517
+ },
518
+ {
519
+ label: `Number of total ${this.dataType}`,
520
+ value: this.numSignificant + this.numNonSignificant
521
+ }
522
+ ];
523
+ if (this.termType == DATermTypes.GENE_EXPRESSION || this.termType == DATermTypes.DNA_METHYLATION || this.termType == DATermTypes.JUNCTION) {
524
+ tableRows.push(
525
+ {
526
+ label: this.config.samplelst.groups[0].name + " sample size (control group)",
527
+ value: this.response.sample_size1
528
+ },
529
+ {
530
+ label: this.config.samplelst.groups[1].name + " sample size (case group)",
531
+ value: this.response.sample_size2
532
+ }
533
+ );
534
+ } else if (this.termType == DATermTypes.PROTEOME_DAP) {
535
+ tableRows.push(
536
+ {
537
+ label: "Control sample size",
538
+ value: this.response.sample_size1
539
+ },
540
+ {
541
+ label: "Case sample size",
542
+ value: this.response.sample_size2
543
+ }
544
+ );
545
+ }
546
+ if (this.response.bcv !== void 0 && this.response.bcv !== null) {
547
+ tableRows.push({
548
+ label: "Biological coefficient of variation",
549
+ value: roundValueAuto(this.response.bcv)
550
+ });
551
+ }
552
+ if (this.scan) tableRows.push(...this.setScanStats(this.scan));
553
+ return tableRows;
554
+ }
555
+ /* The whole-scan facts, every one of them over the scan as returned -- before the volcano's
556
+ thresholds -- and over the same set of DMRs (those meeting the CpG floor), so no two lines here
557
+ have different denominators. The counts the thresholds select are the three rows above. */
558
+ setScanStats(s) {
559
+ const run = s.runChromosomes || s.chromosomes;
560
+ const rows = [
561
+ { label: "Chromosomes scanned", value: run.length },
562
+ // the counts below are over the chromosome shown, the run's genome-wide facts say so in their labels
563
+ ...s.chromosomes.length < run.length ? [{ label: "Chromosomes shown", value: s.chromosomes.join(", ") }] : [],
564
+ { label: "CpGs analyzed", value: s.totalProbesAnalyzed },
565
+ { label: "DMRs called", value: s.called },
566
+ { label: `DMRs with ${s.minCpgs}+ CpGs`, value: s.kept },
567
+ // what the rows below, the Manhattan and the browser track count
568
+ ...s.minDeltaBeta ? [{ label: `\u2026 and |\u0394\u03B2| > ${s.minDeltaBeta}`, value: s.shown }] : [],
569
+ { label: "Hypermethylated", value: s.hyper },
570
+ { label: "Hypomethylated", value: s.hypo },
571
+ // not on the volcano: no evidence to plot, rather than evidence of no change
572
+ ...s.withoutStatistic ? [{ label: `DMRs with no ${this.pValueLabel} (not plotted)`, value: s.withoutStatistic }] : [],
573
+ ...s.withoutDeltaBeta ? [{ label: "DMRs with no \u0394\u03B2 (not plotted or counted)", value: s.withoutDeltaBeta }] : []
574
+ ];
575
+ if (s.width)
576
+ rows.push({
577
+ label: "DMR width, median (IQR)",
578
+ value: `${bplen(s.width.median)} (${bplen(s.width.q1)} \u2013 ${bplen(s.width.q3)})`
579
+ });
580
+ if (s.regionMask)
581
+ rows.push({
582
+ label: `DMRs removed by artifact mask (${s.regionMask.sources.join(", ")}; \u2265${Math.round(
583
+ s.regionMask.overlapFrac * 100
584
+ )}% masked)`,
585
+ value: s.regionMask.dmrsDropped
586
+ });
587
+ const gm = s.globalMethylation;
588
+ if (gm) {
589
+ const [g1, g2] = this.config.samplelst?.groups?.map((g) => g.name) || ["group 1", "group 2"];
590
+ const one = run.length == 1 ? run[0] : null;
591
+ const meanLabel = (g) => one ? `${g} mean \u03B2 on ${one}` : `${g} genome-wide mean \u03B2`;
592
+ rows.push(
593
+ { label: meanLabel(g1), value: gm.controlMeanBeta.toFixed(4) },
594
+ { label: meanLabel(g2), value: gm.caseMeanBeta.toFixed(4) },
595
+ {
596
+ label: one ? `\u03B2 shift on ${one} (case \u2212 control)` : "Genome-wide \u03B2 shift (case \u2212 control)",
597
+ value: `${gm.shift >= 0 ? "+" : ""}${gm.shift.toFixed(4)}`
598
+ }
599
+ );
600
+ const dc = gm.controlMeanDepth, dk = gm.caseMeanDepth;
601
+ if (dc != null && dk != null) {
602
+ rows.push(
603
+ { label: `${g1} mean reads per CpG`, value: dc.toFixed(2) },
604
+ { label: `${g2} mean reads per CpG`, value: dk.toFixed(2) }
605
+ );
606
+ const ratio = Math.max(dc, dk) / Math.min(dc, dk);
607
+ if (ratio > DEPTH_RATIO_WARN) {
608
+ const deeper = dk > dc ? g2 : g1;
609
+ const differ = Number.isFinite(ratio) ? `${deeper} has ${ratio.toFixed(1)}\xD7 the reads per CpG` : `Only ${deeper} has reads`;
610
+ const floor = s.minDeltaBeta ? `only those with |\u0394\u03B2| > ${s.minDeltaBeta} are counted.` : "set Min \u0394\u03B2 to count only DMRs whose beta moved.";
611
+ rows.push({
612
+ label: "\u26A0 Read depth differs between groups",
613
+ value: `${differ}. DMRcate calls DMRs from read-count ratios that shift with depth, so DMRs with little beta change may reflect depth rather than methylation; ${floor}`
614
+ });
615
+ }
616
+ }
617
+ }
618
+ const bc = s.backgroundCorrection;
619
+ if (bc) {
620
+ rows.push(
621
+ {
622
+ label: `Intergenic background windows sampled${s.chromosomes.length < run.length ? " (whole run)" : ""}`,
623
+ value: bc.windows
624
+ },
625
+ { label: `DMRs scored against background (matched on ${bc.matchedOn.join(" and ")})`, value: bc.scored },
626
+ { label: "DMRs unscored: stratum too thin (not plotted)", value: bc.unscored },
627
+ {
628
+ label: "DMRs moving more than matched background (p < 0.05)",
629
+ value: `${bc.significant.toLocaleString()} of ${bc.scored.toLocaleString()} (${(100 * bc.significant / Math.max(1, bc.scored)).toFixed(1)}%)`
630
+ }
631
+ );
632
+ }
633
+ if (s.geneBodyLoss)
634
+ rows.push({
635
+ // the correction adds the background gate, so the label must say which set this is
636
+ label: s.backgroundCorrection ? "Gene-body loss regions beating background \u2192 genes" : "Gene-body loss regions \u2192 genes",
637
+ value: `${s.geneBodyLoss.regions.toLocaleString()} \u2192 ${s.geneBodyLoss.genes.length.toLocaleString()}`
638
+ });
639
+ const pf = s.profileSummary;
640
+ if (pf) {
641
+ const pct = (v) => `${(100 * v).toFixed(1)}%`;
642
+ rows.push(
643
+ {
644
+ label: `Methylome profile: ${pf.bins.toLocaleString()} bins measured`,
645
+ value: `${pct(pf.fractionHyper)} hyper`
646
+ },
647
+ {
648
+ label: "Methylome profile: per-bin \u0394\u03B2, median (IQR)",
649
+ value: `${pf.median >= 0 ? "+" : ""}${pf.median.toFixed(4)} (${pf.q1.toFixed(4)} \u2013 ${pf.q3.toFixed(4)})`
650
+ },
651
+ { label: "Methylome profile: bins moving |\u0394\u03B2| > 0.05", value: pct(pf.fractionBeyond05) },
652
+ { label: "Methylome profile: bins moving |\u0394\u03B2| > 0.10", value: pct(pf.fractionBeyond10) }
653
+ );
654
+ }
655
+ const r = s.resources;
656
+ if (r) {
657
+ const top = r.perChromosome[0];
658
+ rows.push(
659
+ {
660
+ label: "Compute: workers \xD7 threads",
661
+ value: `${r.workers} \xD7 ${r.threadsPerWorker} (${r.workers * r.threadsPerWorker} core${r.workers * r.threadsPerWorker == 1 ? "" : "s"})`
662
+ },
663
+ { label: "Compute: wall time", value: `${(r.wallMs / 1e3).toFixed(1)} s` },
664
+ {
665
+ label: "Compute: peak memory per worker",
666
+ value: `${Math.round(r.peakWorkerMemoryMb).toLocaleString()} MB${top ? ` (${top.chr}, ${top.probes.toLocaleString()} CpGs)` : ""}`
667
+ },
668
+ { label: "Compute: peak memory, worker pool", value: `${Math.round(r.peakPoolMemoryMb).toLocaleString()} MB` },
669
+ { label: "Compute: worker CPU time", value: `${r.workerCpuSeconds.toFixed(1)} s` },
670
+ {
671
+ label: "Compute: server process",
672
+ value: `+${Math.round(r.nodeRssDeltaMb).toLocaleString()} MB, ${r.nodeCpuSeconds.toFixed(1)} s CPU`
673
+ }
674
+ );
675
+ }
676
+ return rows;
677
+ }
678
+ setPTableColumns() {
679
+ if (this.termType == DATermTypes.DNA_METHYLATION) {
680
+ if (this.scan) {
681
+ this.pValueTable.columns.splice(
682
+ 1,
683
+ 0,
684
+ { label: "Peak \u0394\u03B2", sortable: true },
685
+ { label: "CpGs", sortable: true },
686
+ { label: "Width (bp)", sortable: true },
687
+ ...this.scan.backgroundCorrection ? [{ label: "Excess \u0394\u03B2", sortable: true }] : []
688
+ );
689
+ } else {
690
+ this.pValueTable.columns.splice(
691
+ 1,
692
+ 0,
693
+ { label: "\u0394\u03B2", sortable: true },
694
+ { label: "Mean \u03B2 (group 1)", sortable: true },
695
+ { label: "Mean \u03B2 (group 2)", sortable: true }
696
+ );
697
+ }
698
+ this.pValueTable.columns.splice(
699
+ 0,
700
+ 0,
701
+ { label: elementNoun(this.settings?.elementType).one, sortable: true },
702
+ { label: "Gene(s)", sortable: true }
703
+ );
704
+ } else if (this.termType == DATermTypes.JUNCTION) {
705
+ this.pValueTable.columns[0].label = "\u0394PSI";
706
+ this.pValueTable.columns.splice(
707
+ 1,
708
+ 0,
709
+ { label: "PSI (group 1)", sortable: true },
710
+ { label: "PSI (group 2)", sortable: true },
711
+ { label: "Junctions", sortable: true }
712
+ );
713
+ this.pValueTable.columns.splice(0, 0, { label: "Cluster", sortable: true }, { label: "Gene(s)", sortable: true });
714
+ } else if (this.termType == DATermTypes.PROTEOME_DAP) {
715
+ this.pValueTable.columns.splice(0, 0, { label: "Identifier", sortable: true }, { label: "Gene", sortable: true });
716
+ } else {
717
+ this.pValueTable.columns.splice(0, 0, { label: "Gene Name", sortable: true });
718
+ }
719
+ }
720
+ setUserActions() {
721
+ const userActions = {
722
+ noShow: /* @__PURE__ */ new Set()
723
+ };
724
+ if (this.scan) userActions.noShow.add("Confounding factors");
725
+ if (this.termType == DATermTypes.GENE_EXPRESSION) {
726
+ if (this.settings.method == "edgeR" && getSampleNum(this.config) > 100) {
727
+ userActions.noShow.add("Confounding factors");
728
+ }
729
+ if (this.settings.method == "wilcoxon") userActions.noShow.add("Confounding factors");
730
+ }
731
+ return userActions;
732
+ }
733
+ };
734
+
735
+ // plots/volcano/groupColors.ts
736
+ function groupColors(config) {
737
+ const g = config?.samplelst?.groups;
738
+ if (!g?.length) return {};
739
+ const values = config?.tw?.term?.values;
740
+ const pick = (i) => values?.[g[i]?.name]?.color || g[i]?.color;
741
+ const out = {};
742
+ const c1 = pick(0);
743
+ const c2 = pick(1);
744
+ if (c1) out.group1 = c1;
745
+ if (c2) out.group2 = c2;
746
+ return out;
747
+ }
748
+
749
+ // plots/volcano/interactions/VolcanoInteractions.ts
750
+ var VolcanoInteractions = class {
751
+ constructor(app, id, dom) {
752
+ this.app = app;
753
+ this.dom = dom;
754
+ this.id = id;
755
+ this.pValueTableData = [];
756
+ this.data = [];
757
+ this.totalSignificantRows = 0;
758
+ this.provenance = "";
759
+ }
760
+ /** Launches a multi-term select tree
761
+ * On submit, dispatches a plot_edit action with the new confounders */
762
+ async confoundersMenu() {
763
+ const state = this.app.getState();
764
+ const config = state.plots.find((p) => p.id === this.id);
765
+ if (config.termType !== GENE_EXPRESSION && config.termType !== DNA_METHYLATION) return;
766
+ const allowedGroupNames = /* @__PURE__ */ new Set([config.samplelst.groups[0].name, config.samplelst.groups[1].name]);
767
+ const grpTerms = new Set(
768
+ (this.app?.vocabApi?.state.groups || []).filter((g) => allowedGroupNames.has(g.name)).flatMap(
769
+ (g) => g.filter.lst.flatMap((f) => {
770
+ if (f.tvs?.term) return f.tvs.term;
771
+ else return f.lst.map((l) => l.tvs.term);
772
+ })
773
+ )
774
+ );
775
+ const disable_terms = grpTerms.size ? Array.from(grpTerms) : [];
776
+ const maxNum = config.settings.volcano.method == "edgeR" ? 1 : 2;
777
+ const ui = new MultiTermWrapperEditUI({
778
+ app: this.app,
779
+ callback: async (tws) => {
780
+ this.dom.actionsTip.hide();
781
+ await this.app.dispatch({
782
+ type: "plot_edit",
783
+ id: this.id,
784
+ config: { confounderTws: tws }
785
+ });
786
+ },
787
+ holder: this.dom.actionsTip.d,
788
+ headerText: "Select confounders",
789
+ maxNum,
790
+ state,
791
+ twList: config.confounderTws,
792
+ disable_terms
793
+ });
794
+ await ui.renderUI();
795
+ }
796
+ download(termType) {
797
+ this.dom.actionsTip.clear().showunder(this.dom.controls.select("div").node());
798
+ const manhattan = this.dom.holder.select("#sjpp-volcano-scanManhattan > svg").node();
799
+ const profile = this.dom.holder.select('[data-testid="sjpp-volcano-methylationProfile"] svg').node();
800
+ const opts = [
801
+ {
802
+ text: manhattan ? "Download volcano plot" : "Download plot",
803
+ callback: () => {
804
+ const svg = this.dom.holder.select("svg").node();
805
+ to_svg(svg, `Differential ${termType} analysis volcano`, { apply_dom_styles: true });
806
+ }
807
+ },
808
+ ...manhattan ? [{ text: "Download DMR plot", callback: () => downloadManhattanSvg(manhattan, "DMR scan Manhattan") }] : [],
809
+ ...profile ? [
810
+ {
811
+ text: "Download methylation profile",
812
+ callback: () => downloadManhattanSvg(profile, "DMR scan methylation profile")
813
+ }
814
+ ] : [],
815
+ {
816
+ // DAP volcanoes report a single FDR rather than a p-value.
817
+ text: termType === PROTEOME_DAP ? "Download FDR table" : "Download p-value table",
818
+ callback: (itemDiv) => this.downloadPvalueTable(termType, itemDiv)
819
+ }
820
+ ];
821
+ for (const opt of opts) {
822
+ const itemDiv = this.dom.actionsTip.d.append("div").attr("class", "sja_menuoption").text(opt.text);
823
+ itemDiv.on("click", () => opt.callback(itemDiv));
824
+ }
825
+ }
826
+ /* The interactive table only holds the most-significant maxInteractiveDots rows, because the
827
+ dot overlay has to stay responsive. The download has no such constraint, so it should be the
828
+ COMPLETE set of significant rows: when the two differ, re-request with the cap lifted and write
829
+ those rows instead.
830
+
831
+ That second request is cheap. volcanoRender is deliberately not part of the DA cache key (see
832
+ dmKeyInputs in server/routes/termdb.diffMeth.ts), so lifting the cap re-uses the cached R result
833
+ and pays only for a re-render.
834
+
835
+ If the re-request fails the download still happens, with the capped rows and a note saying so --
836
+ losing the file entirely would be a worse outcome than a disclosed subset. */
837
+ async downloadPvalueTable(termType, itemDiv) {
838
+ const date = fileDateStamp();
839
+ const label = termType === PROTEOME_DAP ? "fdr" : "p-value";
840
+ let { rows, columns } = this.pValueTableData;
841
+ let subsetNote;
842
+ const cappedNote = (reason) => `Top ${rows.length.toLocaleString()} of ${this.totalSignificantRows.toLocaleString()} significant results, selected by adjusted p-value and sorted by fold-change. This file is not the complete result set (${reason}).`;
843
+ if (this.totalSignificantRows > rows.length) {
844
+ if (!this.fetchAllRows) subsetNote = cappedNote("complete set unavailable");
845
+ else {
846
+ const restore = itemDiv?.text();
847
+ itemDiv?.text(`Preparing ${this.totalSignificantRows.toLocaleString()} rows...`);
848
+ try {
849
+ const full = await this.fetchAllRows();
850
+ rows = full.rows;
851
+ columns = full.columns;
852
+ } catch (e) {
853
+ subsetNote = cappedNote(`could not retrieve the complete set: ${e?.message || e}`);
854
+ } finally {
855
+ if (restore) itemDiv?.text(restore);
856
+ }
857
+ }
858
+ }
859
+ const note = [subsetNote, this.provenance && `Run: ${this.provenance}`].filter(Boolean).join(" | ");
860
+ downloadTable(rows, columns, `${label}-table-${date}.tsv`, note || void 0);
861
+ }
862
+ async highlightDataPoint(value) {
863
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
864
+ const highlightedData = config.highlightedData.includes(value) ? config.highlightedData.filter((d) => d !== value) : [...config.highlightedData, value];
865
+ await this.app.dispatch({
866
+ type: "plot_edit",
867
+ id: this.id,
868
+ config: { highlightedData }
869
+ });
870
+ }
871
+ /** When clicking on a data point, launches the box plot in a separate sandbox
872
+ * For geneExpression, value == gene symbol */
873
+ launchBoxPlot(value) {
874
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
875
+ const values = {};
876
+ for (const group of config.samplelst.groups) {
877
+ values[group.name] = {
878
+ key: group.name,
879
+ label: group.name,
880
+ list: group.values
881
+ };
882
+ }
883
+ const setTerm = () => {
884
+ if (config.termType == GENE_EXPRESSION) {
885
+ return {
886
+ q: { mode: "continuous" },
887
+ term: {
888
+ gene: value,
889
+ name: value,
890
+ type: config.termType
891
+ }
892
+ };
893
+ } else return config.term;
894
+ };
895
+ this.app.dispatch({
896
+ type: "plot_create",
897
+ config: {
898
+ chartType: "summary",
899
+ childType: "boxplot",
900
+ term: setTerm(),
901
+ term2: {
902
+ q: { groups: config.tw.q.groups, type: "custom-samplelst" },
903
+ term: config.tw.term
904
+ }
905
+ }
906
+ });
907
+ }
908
+ /** Launch a violin plot for a gene expression data point. */
909
+ launchViolinGeneExp(value) {
910
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
911
+ this.app.dispatch({
912
+ type: "plot_create",
913
+ config: {
914
+ chartType: "summary",
915
+ childType: "violin",
916
+ term: {
917
+ q: { mode: "continuous" },
918
+ term: {
919
+ gene: value,
920
+ name: value,
921
+ type: config.termType
922
+ }
923
+ },
924
+ term2: {
925
+ q: { groups: config.tw.q.groups, type: "custom-samplelst" },
926
+ term: config.tw.term
927
+ }
928
+ }
929
+ });
930
+ }
931
+ launchGeneSetEdit() {
932
+ const plotConfig = this.app.getState().plots.find((p) => p.id === this.id);
933
+ const holder = this.dom.actionsTip.d.append("div").style("padding", "5px");
934
+ const limitedGenesList = plotConfig.termType === DNA_METHYLATION ? this.data.map((d) => d.promoter_id) : this.data.map((d) => d.gene_name);
935
+ new GeneSetEditUI({
936
+ holder,
937
+ genome: this.app.opts.genome,
938
+ vocabApi: this.app.vocabApi,
939
+ limitedGenesList,
940
+ geneList: plotConfig.highlightedData.map((d) => {
941
+ return { gene: d };
942
+ }),
943
+ customInputs: [
944
+ {
945
+ label: "Cancel highlight",
946
+ getDisplayStyle: () => plotConfig.highlightedData.length > 0 ? "" : "none",
947
+ showInput: async () => {
948
+ await this.app.dispatch({
949
+ type: "plot_edit",
950
+ id: this.id,
951
+ config: { highlightedData: [] }
952
+ });
953
+ this.dom.actionsTip.hide();
954
+ }
955
+ }
956
+ ],
957
+ callback: async (result) => {
958
+ const highlightedData = result.geneList.map((d) => d.gene);
959
+ await this.app.dispatch({
960
+ type: "plot_edit",
961
+ id: this.id,
962
+ config: { highlightedData }
963
+ });
964
+ this.dom.actionsTip.hide();
965
+ }
966
+ });
967
+ }
968
+ /** Opens the region view on a DMR of a scan: a window on the scan's own DMRcate run -- its
969
+ * chromosomes, lambda, C and FDR -- so it draws the DMRs the volcano drew, from the cache. Takes the
970
+ * scan rather than a region alone so it cannot be opened from an element class, whose hits come
971
+ * from another test: a per-element comparison that DMRcate's de novo calls need not agree with. */
972
+ async launchDmr(d, scan) {
973
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
974
+ const colors = groupColors(config);
975
+ const s = config.settings.volcano;
976
+ const termfilter = this.app.getState().termfilter;
977
+ const groups = withOthersGroup(config.samplelst.groups, termfilter);
978
+ const k = scan.dmrcate;
979
+ const dmrConfig = {
980
+ chartType: "dmr",
981
+ headerText: `DMR: ${d.chr}:${d.start}-${d.stop}`,
982
+ coordinateOverride: { chr: d.chr, start: d.start, stop: d.stop },
983
+ // the samples of each group, or the filter of a group that is defined by one
984
+ group1: getGroupForRegion(groups[0]),
985
+ group2: getGroupForRegion(groups[1]),
986
+ group1Name: groups[0].name,
987
+ group2Name: groups[1].name,
988
+ settings: {
989
+ colors,
990
+ lambda: k?.lambda ?? s.lambda,
991
+ C: k?.C ?? s.C,
992
+ fdr_cutoff: k?.fdr_cutoff ?? s.fdrCutoff,
993
+ // the floor the scan's counts were made with, which the control may since have left
994
+ minDeltaBeta: scan.minDeltaBeta
995
+ },
996
+ scanChromosomes: scan.runChromosomes,
997
+ // also in the run's cache key, so the region finds the scan's run rather than refitting it
998
+ backgroundCorrection: !!scan.backgroundCorrection,
999
+ // the scan drops DMRs with fewer CpGs; the region view drops them too
1000
+ minCpgs: scan.minCpgs,
1001
+ // and the DMRs without its y-axis statistic
1002
+ yAxis: scan.yAxis,
1003
+ /* the cohort filter the scan request sent, which resolves a filter-defined group that carries none
1004
+ of its own; a different cohort would be a different run */
1005
+ filter0: termfilter.filter0,
1006
+ ...scan.globalMethylation?.controlMeanDepth != null && scan.globalMethylation?.caseMeanDepth != null ? {
1007
+ readDepth: {
1008
+ control: scan.globalMethylation.controlMeanDepth,
1009
+ case: scan.globalMethylation.caseMeanDepth
1010
+ }
1011
+ } : {}
1012
+ };
1013
+ this.app.dispatch({
1014
+ type: "plot_create",
1015
+ config: dmrConfig
1016
+ });
1017
+ }
1018
+ /* Open a genome browser on a scan's DMR, with the scan's own DMRs as a track. The scan wrote
1019
+ every DMR it called to a bedj file in the server's cache (at the CpG floor the volcano counts
1020
+ at), so the track is an ordinary file tk: the browser reads whatever region is in view from it,
1021
+ including after the reader types another position into the search box. Opened on the DMR with
1022
+ room either side. */
1023
+ /** A genome browser on a methylation hit: a scan's DMR, with the scan's DMRs as a track, or an element-class hit
1024
+ * (promoter, cCRE), with the genes and cCREs around it and no DMR track, since no DMRs were called */
1025
+ async launchMethylationGenomeBrowser(d, scan) {
1026
+ const tracks = [];
1027
+ const ccre = (this.app.opts.genome?.tracks || []).find((t) => t.name == CCRE_TRACK_NAME);
1028
+ if (ccre) tracks.push(structuredClone(ccre));
1029
+ if (scan?.bedjFile) {
1030
+ tracks.push({
1031
+ type: "bedj",
1032
+ name: "Scan DMRs",
1033
+ // the file is under the server's bedj cache dir, not the tp dir
1034
+ isCache: true,
1035
+ file: scan.bedjFile,
1036
+ stackheight: 14,
1037
+ // drives both the fill and the block legend, which counts each class in view
1038
+ categories: {
1039
+ hyper: { label: "Hypermethylated DMR", color: HYPER_COLOR },
1040
+ hypo: { label: "Hypomethylated DMR", color: HYPO_COLOR }
1041
+ }
1042
+ });
1043
+ }
1044
+ const pad = Math.max(5e3, d.stop - d.start);
1045
+ this.app.dispatch({
1046
+ type: "plot_create",
1047
+ config: {
1048
+ chartType: "genomeBrowser",
1049
+ // a coordinate with no gene: genomic mode, whatever mode the dataset defaults the browser to
1050
+ blockIsProteinMode: false,
1051
+ geneSearchResult: { chr: d.chr, start: Math.max(0, d.start - pad), stop: d.stop + pad },
1052
+ tracks
1053
+ }
1054
+ });
1055
+ }
1056
+ /* Open a genome browser on an intron cluster, with its junctions as a track whose y is the
1057
+ -log10 p of each junction and whose color tells the group with higher PSI.
1058
+ The junctions come from the cached data, by re-sending the analysis request with the cluster id. */
1059
+ async launchSpliceGenomeBrowser(d) {
1060
+ const data = await dofetch3("termdb/diffSplice", { body: { ...this.daRequest, clusterId: d.cluster_id } });
1061
+ if (data.error) {
1062
+ sayerror(this.dom.error, data.error);
1063
+ return;
1064
+ }
1065
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
1066
+ const { caseColor, controlColor } = getGroupColors(config);
1067
+ const cluster = d.cluster_id.slice(d.cluster_id.indexOf(":") + 1);
1068
+ const strand = cluster.split("_").pop();
1069
+ const pad = Math.max(500, Math.round((d.stop - d.start) * 0.2));
1070
+ this.app.dispatch({
1071
+ type: "plot_create",
1072
+ config: {
1073
+ chartType: "genomeBrowser",
1074
+ // as for a scan DMR: a coordinate with no gene opens in genomic mode
1075
+ blockIsProteinMode: false,
1076
+ // cluster start/stop are the 1-based exon boundaries; the junctions are already 0-based
1077
+ geneSearchResult: { chr: d.chr, start: Math.max(0, d.start - 1 - pad), stop: d.stop + pad },
1078
+ tracks: [
1079
+ {
1080
+ type: "j2",
1081
+ name: d.genes ? `${d.genes} ${cluster}` : cluster,
1082
+ custom_data: data.junctions.map((j) => ({ ...j, strand })),
1083
+ deltaPsiGroups: {
1084
+ control: { name: config.samplelst.groups[0].name, color: controlColor },
1085
+ case: { name: config.samplelst.groups[1].name, color: caseColor }
1086
+ }
1087
+ }
1088
+ ]
1089
+ }
1090
+ });
1091
+ }
1092
+ /** Launch a violin/box plot for a DNA methylation promoter.
1093
+ * Creates a methylation term using the promoter's chr/start/stop coordinates.
1094
+ * The tw handler fills in id and unit from termdbConfig. */
1095
+ launchDNAMethViolin(d) {
1096
+ const config = this.app.getState().plots.find((p) => p.id === this.id);
1097
+ const elementType = config?.settings?.volcano?.elementType;
1098
+ const genomicFeatureType = elementType === DMR_SCAN_ELEMENT_TYPE ? "region" : d.promoter_id ? "promoter" : "gene";
1099
+ const featureName = genomicFeatureType === "gene" ? d.gene_name?.split(",")[0]?.trim() || "" : "";
1100
+ const term = {
1101
+ genomicFeatureType,
1102
+ featureName,
1103
+ type: DNA_METHYLATION,
1104
+ chr: d.chr,
1105
+ start: d.start,
1106
+ stop: d.stop
1107
+ };
1108
+ if (genomicFeatureType === "promoter" && elementType) term.elementType = elementType;
1109
+ if (genomicFeatureType !== "gene") {
1110
+ const noun = elementNoun(elementType).one;
1111
+ const unit = term.elementType && this.app.vocabApi.termdbConfig.queries?.dnaMethylation?.unit || getDNAMethUnit(genomicFeatureType, this.app.vocabApi);
1112
+ term.unit = unit;
1113
+ term.name = getDNAMethTermName(term, unit, noun);
1114
+ }
1115
+ this.app.dispatch({
1116
+ type: "plot_create",
1117
+ config: {
1118
+ chartType: "summary",
1119
+ childType: "violin",
1120
+ term: {
1121
+ q: { mode: "continuous" },
1122
+ term
1123
+ },
1124
+ term2: {
1125
+ q: { groups: config.tw.q.groups, type: "custom-samplelst" },
1126
+ term: config.tw.term
1127
+ }
1128
+ }
1129
+ });
1130
+ }
1131
+ async launchDEGClustering() {
1132
+ const geneIndex = this.pValueTableData.columns.findIndex((col) => col.label === "Gene Name");
1133
+ const adjustedPValIndex = this.pValueTableData.columns.findIndex((col) => col.label === "Adjusted p-value");
1134
+ const rowsSorted = [...this.pValueTableData.rows].sort((a, b) => {
1135
+ const aQVal = Number(a[adjustedPValIndex].value);
1136
+ const bQVal = Number(b[adjustedPValIndex].value);
1137
+ return aQVal - bQVal;
1138
+ });
1139
+ const geneList = rowsSorted.slice(0, 100).map((r) => ({ gene: r[geneIndex].value }));
1140
+ const tws = geneList.map((d) => {
1141
+ const gene = d.gene;
1142
+ const unit = getGEunit(this.app.vocabApi);
1143
+ const name = `${gene} ${unit}`;
1144
+ const term = { gene, name, type: GENE_EXPRESSION };
1145
+ return { term, q: {} };
1146
+ });
1147
+ const group = { lst: tws, type: "hierCluster" };
1148
+ const customVariable = this.app.getState().plots.find((p) => p.id === this.id).tw;
1149
+ const annotationGroup = { lst: [customVariable] };
1150
+ const config = {
1151
+ chartType: "hierCluster",
1152
+ termgroups: [group, annotationGroup],
1153
+ dataType: GENE_EXPRESSION,
1154
+ filter: {
1155
+ in: true,
1156
+ join: "",
1157
+ type: "tvslst",
1158
+ lst: [{ type: "tvs", tvs: { term: customVariable.term } }]
1159
+ }
1160
+ };
1161
+ await this.app.dispatch({
1162
+ type: "plot_create",
1163
+ config: structuredClone(config)
1164
+ });
1165
+ }
1166
+ };
1167
+
1168
+ // plots/volcano/interactions/geneBodyLossDE.ts
1169
+ async function geneBodyLossTest(tip, config, vocab, scan, app) {
1170
+ const gb = scan.geneBodyLoss;
1171
+ const holder = tip.d;
1172
+ const groups = (scan.matchedSamplelst || config?.samplelst)?.groups;
1173
+ if (!groups || groups.length != 2) {
1174
+ sayerror(holder.append("div"), "Two sample groups are required.");
1175
+ return;
1176
+ }
1177
+ const div = holder.append("div").style("padding", "10px").style("max-width", "900px");
1178
+ const wait = div.append("div").style("color", "#777").text("Running differential expression\u2026");
1179
+ const de = getDefaultVolcanoSettings({}, { termType: "geneExpression" });
1180
+ try {
1181
+ const res = await dofetch3("termdb/dmrGeneDE", {
1182
+ body: {
1183
+ genome: vocab.genome,
1184
+ dslabel: vocab.dslabel,
1185
+ // `in` is part of the DE cache key, so it must travel or the two runs get separate entries
1186
+ samplelst: {
1187
+ groups: groups.map((g) => ({
1188
+ name: g.name,
1189
+ in: g.in,
1190
+ values: g.values,
1191
+ filter: g.filter,
1192
+ filter0: g.filter0,
1193
+ mapParent2Children: g.mapParent2Children
1194
+ }))
1195
+ },
1196
+ genes: gb.genes,
1197
+ method: de.method,
1198
+ min_count: de.minCount,
1199
+ min_total_count: de.minTotalCount,
1200
+ cpm_cutoff: de.cpmCutoff,
1201
+ filter: app.getState().termfilter?.filter,
1202
+ filter0: app.getState().termfilter?.filter0
1203
+ }
1204
+ });
1205
+ wait.remove();
1206
+ if (res?.error) {
1207
+ sayerror(div.append("div"), res.error);
1208
+ return;
1209
+ }
1210
+ renderGeneDE(div, res, gb.regions, config, scan, app, tip);
1211
+ } catch (e) {
1212
+ wait.remove();
1213
+ sayerror(div.append("div"), e?.message || String(e));
1214
+ }
1215
+ }
1216
+ function renderGeneDE(div, res, nRegions, config, scan, app, tip) {
1217
+ const gb = scan.geneBodyLoss;
1218
+ const samplelst = scan.matchedSamplelst || config.samplelst;
1219
+ const nMatched = samplelst.groups.reduce((n, g) => n + (g.values?.length ?? g.sampleCount ?? 0), 0);
1220
+ const dir = res.weightedDiff < 0 ? "lower" : "higher";
1221
+ div.append("button").attr("class", "sja_menuoption").attr("data-testid", "sjpp-geneBodyLoss-deVolcano").style("margin", "0 0 8px").style("padding", "3px 6px").text(
1222
+ `Open as differential expression volcano on the ${nMatched.toLocaleString()} samples with methylation, ${gb.genes.length.toLocaleString()} genes highlighted`
1223
+ ).on("click", () => {
1224
+ tip.hide();
1225
+ app.dispatch({
1226
+ type: "plot_create",
1227
+ config: structuredClone({
1228
+ chartType: "differentialAnalysis",
1229
+ termType: "geneExpression",
1230
+ state: config.state,
1231
+ samplelst,
1232
+ tw: config.tw,
1233
+ highlightedData: gb.genes,
1234
+ /* The default highlight is orange-yellow, which on a case group drawn in orange makes
1235
+ the highlighted hits and the up-regulated genes one blob. Use the colour the
1236
+ methylation figures give to LOSS instead: these genes are highlighted because they
1237
+ lost gene-body methylation, so the fill says the same thing there and here. */
1238
+ settings: { volcano: { defaultHighlightColor: HYPO_COLOR } }
1239
+ })
1240
+ });
1241
+ });
1242
+ div.append("div").style("font-weight", "bold").style("padding", "4px 0").text(
1243
+ `Genes under a gene-body loss region are expressed ${dir} in the case group: ${res.weightedDiff >= 0 ? "+" : ""}${res.weightedDiff.toFixed(3)} log\u2082 fold change within matched gene length (p = ${res.p < 1e-3 ? res.p.toExponential(1) : res.p.toFixed(4)}).`
1244
+ );
1245
+ div.append("div").style("color", "#777").style("font-size", ".92em").text(
1246
+ `${nRegions.toLocaleString()} regions \u2192 ${res.genesRequested.toLocaleString()} genes; ${res.nHit.toLocaleString()} compared against ${res.nOther.toLocaleString()} genes of matched length across ${res.strata.length} strata. ${res.genesNotInDE.toLocaleString()} were not tested by DE (low count or absent from the expression matrix) and ${res.unmatchedHits.toLocaleString()} fell in strata too thin to match. Comparing hits to all other genes instead would recover gene length.`
1247
+ );
1248
+ if (res.sigCount) {
1249
+ div.append("div").style("padding", "8px 0 2px").style("font-weight", "bold").text(
1250
+ `${res.sigCount.toLocaleString()} of these genes are differentially expressed on their own (p < 0.05), ${res.sigDown.toLocaleString()} of them down.`
1251
+ );
1252
+ const { caseColor, controlColor } = getGroupColors(config);
1253
+ renderTable({
1254
+ div: div.append("div"),
1255
+ columns: [
1256
+ { label: "Gene" },
1257
+ { label: "Length (log\u2081\u2080 bp)", barplot: { axisWidth: 90, colorPositive: "#999", tickCount: 3 } },
1258
+ { label: "log\u2082FC", barplot: { axisWidth: 110, colorNegative: controlColor, colorPositive: caseColor } },
1259
+ { label: res.topGenes[0]?.adjusted ? "Adjusted p" : "p", align: "right" }
1260
+ ],
1261
+ rows: res.topGenes.map((g) => [
1262
+ { value: g.gene },
1263
+ { value: g.len ? Number(Math.log10(g.len).toFixed(2)) : NaN },
1264
+ { value: Number(g.fc.toFixed(3)) },
1265
+ { value: Number(g.p.toPrecision(2)) }
1266
+ ]),
1267
+ showLines: true,
1268
+ maxHeight: "26vh",
1269
+ download: { fileName: "gene-body-loss-genes.tsv" }
1270
+ });
1271
+ if (res.sigCount > res.topGenes.length)
1272
+ div.append("div").style("color", "#777").style("font-size", ".9em").text(`Showing the ${res.topGenes.length} most significant of ${res.sigCount.toLocaleString()}.`);
1273
+ }
1274
+ div.append("div").style("padding", "10px 0 2px").style("font-weight", "bold").text("By gene length");
1275
+ renderTable({
1276
+ div: div.append("div"),
1277
+ columns: [
1278
+ { label: "Gene length" },
1279
+ { label: "Genes hit", align: "right" },
1280
+ { label: "Matched", align: "right" },
1281
+ { label: "Median log\u2082FC, hit", align: "right" },
1282
+ { label: "Median log\u2082FC, matched", align: "right" },
1283
+ { label: "Difference", align: "right" }
1284
+ ],
1285
+ rows: res.strata.map((s) => [
1286
+ { value: `${bplen(s.lenFrom)} \u2013 ${bplen(s.lenTo)}` },
1287
+ { value: s.nHit.toLocaleString() },
1288
+ { value: s.nOther.toLocaleString() },
1289
+ { value: Number(s.medianHit.toFixed(3)) },
1290
+ { value: Number(s.medianOther.toFixed(3)) },
1291
+ { value: Number(s.diff.toFixed(3)) }
1292
+ ]),
1293
+ showLines: true,
1294
+ maxHeight: "26vh",
1295
+ download: { fileName: "gene-body-loss-expression.tsv" }
1296
+ });
1297
+ }
1298
+
1299
+ // plots/volcano/interactions/dmrGeneLink.ts
1300
+ async function dmrGeneLinkPanel(tip, config, vocab, scan, app) {
1301
+ const div = tip.d.append("div").style("padding", "10px").style("max-width", "1000px");
1302
+ const wait = div.append("div").style("color", "#777").text("Linking DMRs to genes and running differential expression\u2026");
1303
+ const de = getDefaultVolcanoSettings({}, { termType: "geneExpression" });
1304
+ const state = app.getState();
1305
+ let res;
1306
+ try {
1307
+ res = await dofetch3("termdb/dmrGeneLink", {
1308
+ body: {
1309
+ genome: vocab.genome,
1310
+ dslabel: vocab.dslabel,
1311
+ cacheId: scan.cacheId,
1312
+ minCpgs: scan.minCpgs,
1313
+ minDeltaBeta: scan.minDeltaBeta,
1314
+ // the run is genome-wide; the volcano may be showing a part of it
1315
+ chromosomes: scan.chromosomes,
1316
+ /* The cohort the scan compared, expanded and matched server-side. The plot state's list can still
1317
+ hold a "Not in" group as {in:false} carrying the included group's values, which DE reads as two
1318
+ overlapping groups. */
1319
+ samplelst: {
1320
+ groups: (scan.matchedSamplelst || config.samplelst).groups.map((g) => ({
1321
+ name: g.name,
1322
+ in: g.in,
1323
+ values: g.values,
1324
+ filter: g.filter,
1325
+ filter0: g.filter0,
1326
+ mapParent2Children: g.mapParent2Children
1327
+ }))
1328
+ },
1329
+ method: de.method,
1330
+ min_count: de.minCount,
1331
+ min_total_count: de.minTotalCount,
1332
+ cpm_cutoff: de.cpmCutoff,
1333
+ filter: state.termfilter?.filter,
1334
+ filter0: state.termfilter?.filter0
1335
+ }
1336
+ });
1337
+ } catch (e) {
1338
+ res = { error: e?.message || String(e) };
1339
+ }
1340
+ wait.remove();
1341
+ if (res.error) return sayerror(div.append("div"), res.error);
1342
+ div.append("div").style("font-weight", "bold").text(
1343
+ `${res.genes.toLocaleString()} genes touched by DMRs of ${scan.minCpgs}+ CpGs (${res.links.toLocaleString()} gene-context links), read against ${res.deMethod || "differential"} expression on the samples with methylation`
1344
+ );
1345
+ div.append("div").style("color", "#777").style("font-size", ".92em").style("padding", "2px 0 6px").text(
1346
+ `Promoter = within ${bplen(
1347
+ 2e3
1348
+ )} of the TSS; body = the rest of the gene. Concordant: promoter \u0394\u03B2 and expression change in opposite directions, or gene-body \u0394\u03B2 and expression in the same direction (expression adjusted p < 0.05).`
1349
+ );
1350
+ const summary = table2col({ holder: div.append("div") });
1351
+ for (const context of ["promoter", "body"]) {
1352
+ const s = res.summary[context] || {};
1353
+ const [td1, td2] = summary.addRow();
1354
+ td1.text(context == "promoter" ? "Promoter DMRs" : "Gene-body DMRs");
1355
+ td2.text(
1356
+ ["concordant", "discordant", "no expression change", "not tested"].map((k) => `${k}: ${(s[k] || 0).toLocaleString()}`).join(" \xB7 ")
1357
+ );
1358
+ }
1359
+ const rows = res.rows;
1360
+ const litDiv = div.append("div");
1361
+ const recordOf = /* @__PURE__ */ new Map();
1362
+ const tableRows = rows.map((r) => {
1363
+ const cells = [
1364
+ { value: r.gene },
1365
+ { value: r.context },
1366
+ { value: `${r.dmr.chr}:${r.dmr.start}-${r.dmr.stop}` },
1367
+ { value: Number(r.dmr.deltaBeta.toFixed(3)) },
1368
+ { value: r.dmr.cpgs },
1369
+ { value: r.nDmrs },
1370
+ { value: r.fc == null ? "" : Number(r.fc.toFixed(3)) },
1371
+ { value: r.p == null ? "" : Number(r.p.toPrecision(2)) },
1372
+ { value: r.relationship }
1373
+ ];
1374
+ recordOf.set(cells, r);
1375
+ return cells;
1376
+ });
1377
+ renderTable({
1378
+ div: div.append("div"),
1379
+ columns: [
1380
+ { label: "Gene" },
1381
+ { label: "Context" },
1382
+ { label: "Strongest DMR" },
1383
+ { label: "\u0394\u03B2", sortable: true },
1384
+ { label: "CpGs", sortable: true },
1385
+ { label: "DMRs", sortable: true },
1386
+ { label: "Expression log\u2082FC", sortable: true },
1387
+ { label: "Expression p", sortable: true },
1388
+ { label: "Relationship" }
1389
+ ],
1390
+ rows: tableRows,
1391
+ showLines: true,
1392
+ maxHeight: "40vh",
1393
+ header: { allowSort: true },
1394
+ noRadioBtn: true,
1395
+ download: { fileName: "dmr-gene-links.tsv" },
1396
+ // a click asks PubMed about that row's gene in that row's context
1397
+ noButtonCallback: (i) => showLiterature(litDiv, vocab, recordOf.get(tableRows[i]), disease)
1398
+ });
1399
+ if (rows.length < res.links)
1400
+ div.append("div").style("color", "#777").style("font-size", ".9em").text(`Showing the first ${rows.length.toLocaleString()} of ${res.links.toLocaleString()} links.`);
1401
+ const hint = litDiv.append("div").style("color", "#777").style("padding", "6px 0");
1402
+ hint.append("span").text("Click a row for PubMed articles on that gene and mechanism, optionally within a disease: ");
1403
+ const disease = hint.append("input").attr("type", "text").attr("placeholder", "e.g. myeloma").style("width", "120px");
1404
+ }
1405
+ async function showLiterature(holder, vocab, r, disease) {
1406
+ holder.selectAll(".sjpp-dmr-lit").remove();
1407
+ const out = holder.append("div").attr("class", "sjpp-dmr-lit");
1408
+ const head = out.append("div").style("padding", "8px 0 2px").style("font-weight", "bold");
1409
+ const d = String(disease?.property("value") || "").trim();
1410
+ const within = d ? ` in ${d}` : "";
1411
+ head.text(`PubMed: ${r.gene}, ${r.context} methylation and expression${within}\u2026`);
1412
+ const res = await dofetch3("termdb/dmrLiterature", {
1413
+ body: { genome: vocab.genome, dslabel: vocab.dslabel, gene: r.gene, context: r.context, disease: d }
1414
+ }).catch((e) => ({ error: e?.message || String(e) }));
1415
+ holder = out;
1416
+ if (res.error) return sayerror(holder.append("div"), res.error);
1417
+ head.text(
1418
+ `PubMed: ${r.gene}, ${r.context} methylation and expression${within} (${res.count.toLocaleString()} article${res.count == 1 ? "" : "s"}${res.count > res.articles.length ? `, ${res.articles.length} most relevant shown` : ""}; this link is ${r.relationship})`
1419
+ );
1420
+ if (!res.articles.length) {
1421
+ holder.append("div").style("color", "#777").text("No articles match. The link may be unreported rather than unsupported.");
1422
+ return;
1423
+ }
1424
+ const ul = holder.append("ul").style("margin", "2px 0");
1425
+ for (const a of res.articles) {
1426
+ const li = ul.append("li");
1427
+ li.append("span").text(`${a.title} ${a.journal} ${a.year}. `);
1428
+ li.append("a").attr("href", a.doi ? `https://doi.org/${a.doi}` : `https://pubmed.ncbi.nlm.nih.gov/${a.pmid}/`).attr("target", "_blank").text(a.doi ? `doi:${a.doi}` : `PMID ${a.pmid}`);
1429
+ }
1430
+ }
1431
+
1432
+ // plots/volcano/view/VolcanoPlotView.ts
1433
+ var VolcanoPlotView = class {
1434
+ constructor(dom, interactions, termType) {
1435
+ this.linked = [];
1436
+ this.dom = dom;
1437
+ this.interactions = interactions;
1438
+ this.termType = termType;
1439
+ const actions = this.dom.holder.append("div").attr("id", "sjpp-volcano-actions").style("display", "block").style("z-index", 1).style("position", "relative");
1440
+ this.row = this.dom.holder.append("div").attr("id", "sjpp-volcano-row").style("display", "flex").style("align-items", "flex-start");
1441
+ const svg = this.row.append("svg").style("display", "inline-block").attr("id", "sjpp-volcano-svg").style("vertical-align", "top");
1442
+ this.volcanoDom = {
1443
+ actions,
1444
+ svg,
1445
+ pValueTable: void 0,
1446
+ top: void 0,
1447
+ xAxis: void 0,
1448
+ xAxisLabel: void 0,
1449
+ yAxis: void 0,
1450
+ yAxisLabel: void 0,
1451
+ plot: void 0
1452
+ };
1453
+ }
1454
+ render(settings, viewData) {
1455
+ this.settings = settings;
1456
+ this.viewData = viewData;
1457
+ this.linked = [];
1458
+ const plotDim = this.viewData.plotDim;
1459
+ this.initDom();
1460
+ this.renderUserActions();
1461
+ this.renderPlot(plotDim);
1462
+ renderDataPoints(this);
1463
+ this.renderFoldChangeLine(plotDim);
1464
+ this.attachInteractions(plotDim);
1465
+ if (this.settings.showPValueTable) this.renderPValueTable();
1466
+ if (this.viewData.scan?.manhattan) this.renderScanManhattan();
1467
+ }
1468
+ initDom() {
1469
+ this.volcanoDom.actions.selectAll("*").remove();
1470
+ this.volcanoDom.svg.selectAll("*").remove();
1471
+ const svg = this.volcanoDom.svg;
1472
+ this.volcanoDom.top = svg.append("g").attr("id", "sjpp-volcano-top");
1473
+ this.volcanoDom.xAxis = svg.append("g").attr("id", "sjpp-volcano-xAxis");
1474
+ this.volcanoDom.yAxis = svg.append("g").attr("id", "sjpp-volcano-yAxis");
1475
+ this.volcanoDom.xAxisLabel = svg.append("text").attr("id", "sjpp-volcano-xAxisLabel").attr("text-anchor", "middle");
1476
+ this.volcanoDom.yAxisLabel = svg.append("text").attr("id", "sjpp-volcano-yAxisLabel").attr("text-anchor", "middle");
1477
+ this.volcanoDom.plot = svg.append("g").attr("id", "sjpp-volcano-plot");
1478
+ this.dom.holder.select("#sjpp-volcano-pValueTable").remove();
1479
+ this.dom.holder.select("#sjpp-volcano-scanManhattan").remove();
1480
+ if (!this.settings.showPValueTable) return;
1481
+ this.volcanoDom.pValueTable = this.row.append("div").attr("id", "sjpp-volcano-pValueTable").attr("data-testid", "sjpp-volcano-pValueTable").style("display", "inline-block").style("vertical-align", "top");
1482
+ }
1483
+ renderUserActions() {
1484
+ this.dom.actionsTip.d.style("overflow", "hidden");
1485
+ this.volcanoDom.actions.style("margin-left", "20px").style("padding", "5px");
1486
+ this.addActionButton(
1487
+ "Confounding factors",
1488
+ [DATermTypes.GENE_EXPRESSION, DATermTypes.DNA_METHYLATION],
1489
+ () => this.interactions.confoundersMenu()
1490
+ );
1491
+ this.addActionButton(
1492
+ "Highlight genes",
1493
+ [DATermTypes.GENE_EXPRESSION, DATermTypes.SINGLECELL_CELLTYPE, DATermTypes.DNA_METHYLATION],
1494
+ () => this.interactions.launchGeneSetEdit()
1495
+ );
1496
+ this.addActionButton(
1497
+ "Statistics",
1498
+ [DATermTypes.GENE_EXPRESSION, DATermTypes.SINGLECELL_CELLTYPE, DATermTypes.DNA_METHYLATION],
1499
+ () => {
1500
+ this.renderStatsMenu();
1501
+ },
1502
+ { whenOpen: "Hide statistics" }
1503
+ );
1504
+ const gb = this.viewData.scan?.geneBodyLoss;
1505
+ const hasExpression = !!this.interactions.app.vocabApi.termdbConfig?.queries?.rnaseqGeneCount;
1506
+ if (hasExpression && gb?.genes.length) {
1507
+ this.addActionButton(
1508
+ `Expression of ${gb.genes.length.toLocaleString()} gene-body loss genes`,
1509
+ [DATermTypes.DNA_METHYLATION],
1510
+ () => geneBodyLossTest(
1511
+ this.dom.actionsTip,
1512
+ this.interactions.app.getState().plots.find((p) => p.id == this.interactions.id),
1513
+ this.interactions.app.vocabApi.vocab,
1514
+ this.viewData.scan,
1515
+ this.interactions.app
1516
+ )
1517
+ );
1518
+ }
1519
+ if (hasExpression && this.viewData.scan?.cacheId) {
1520
+ this.addActionButton(
1521
+ "Genes, expression and literature",
1522
+ [DATermTypes.DNA_METHYLATION],
1523
+ () => dmrGeneLinkPanel(
1524
+ this.dom.actionsTip,
1525
+ this.interactions.app.getState().plots.find((p) => p.id == this.interactions.id),
1526
+ this.interactions.app.vocabApi.vocab,
1527
+ this.viewData.scan,
1528
+ this.interactions.app
1529
+ )
1530
+ );
1531
+ }
1532
+ const dmNoun = elementNoun(this.settings?.elementType);
1533
+ const SIG_PREFIX = "Number of significant ";
1534
+ const sigRow = this.viewData.statsData.find((d) => d.label.startsWith(SIG_PREFIX));
1535
+ const numSigGenes = Number(sigRow?.value ?? 0);
1536
+ if (numSigGenes) {
1537
+ const n = numSigGenes.toLocaleString();
1538
+ const isDM = this.termType == DATermTypes.DNA_METHYLATION;
1539
+ const up = this.viewData.numSignificantUp;
1540
+ const down = this.viewData.numSignificantDown;
1541
+ const split = up + down > 0 ? ` (${up.toLocaleString()} ${isDM ? "hyper" : "up"} / ${down.toLocaleString()} ${isDM ? "hypo" : "down"})` : "";
1542
+ const off = this.viewData.xOffset;
1543
+ const centered = this.viewData.centered ? `, centered on median \u0394\u03B2 ${off > 0 ? "+" : ""}${off.toFixed(3)}` : "";
1544
+ const noun = isDM ? this.viewData.scan ? dmNoun.many : `DM ${dmNoun.many}` : this.termType == DATermTypes.GENE_EXPRESSION ? "DE genes" : `significant ${sigRow.label.slice(SIG_PREFIX.length)}`;
1545
+ const sigText = `${n} ${noun}` + split + centered + ":";
1546
+ this.volcanoDom.actions.append("span").text(sigText).style("margin-left", "10px").style("font-weight", "bold");
1547
+ const pValueTableButtonText = this.settings.showPValueTable ? "Hide p-value table" : "Show p-value table";
1548
+ this.addActionButton(
1549
+ pValueTableButtonText,
1550
+ [DATermTypes.GENE_EXPRESSION, DATermTypes.SINGLECELL_CELLTYPE, DATermTypes.DNA_METHYLATION],
1551
+ async () => {
1552
+ const showTable = !this.settings.showPValueTable;
1553
+ await this.interactions.app.dispatch({
1554
+ type: "plot_edit",
1555
+ id: this.interactions.id,
1556
+ config: { settings: { volcano: { showPValueTable: showTable } } }
1557
+ });
1558
+ }
1559
+ );
1560
+ }
1561
+ if (numSigGenes && numSigGenes >= 3) {
1562
+ this.addActionButton(
1563
+ `Hierarchical clustering of ${numSigGenes > 100 ? "top 100" : numSigGenes} DE genes`,
1564
+ [DATermTypes.GENE_EXPRESSION],
1565
+ async () => {
1566
+ await this.interactions.launchDEGClustering();
1567
+ }
1568
+ );
1569
+ }
1570
+ }
1571
+ /** Use the termTypes arr to render the buttons in a consistent order.
1572
+ *
1573
+ * Pass `opts.whenOpen` to make the button a toggle: clicking once opens
1574
+ * the actionsTip with the callback's content and swaps the button text
1575
+ * to `whenOpen` ("Hide statistics", etc.); clicking again hides the tip
1576
+ * and restores the original text. The text also restores when the tip
1577
+ * closes via Esc or outside-click (Menu.onHide hook), and when another
1578
+ * action button hijacks the tip (the loop below resets all toggles
1579
+ * before showing the new content). */
1580
+ addActionButton(text, termTypes, callback, opts) {
1581
+ if (this.viewData.userActions.noShow.has(text)) return;
1582
+ if (!termTypes.includes(this.termType)) return;
1583
+ const button = this.volcanoDom.actions.append("button").attr("class", "sja_menuoption").style("margin", "3px").style("padding", "3px").text(text).on("click", async () => {
1584
+ const whenOpen = opts?.whenOpen;
1585
+ if (whenOpen && button.text() === whenOpen) {
1586
+ this.dom.actionsTip.hide();
1587
+ return;
1588
+ }
1589
+ this.volcanoDom.actions.selectAll('button[data-volcano-toggle-open="1"]').each(function() {
1590
+ const b = select_default(this);
1591
+ const closed = b.attr("data-volcano-toggle-closed");
1592
+ if (closed) b.text(closed).attr("data-volcano-toggle-open", null);
1593
+ this.parent_menu = void 0;
1594
+ const eh = this.__volcanoEscHandler;
1595
+ if (eh) {
1596
+ document.removeEventListener("keydown", eh);
1597
+ this.__volcanoEscHandler = void 0;
1598
+ }
1599
+ });
1600
+ this.dom.actionsTip.clear().showunder(button.node());
1601
+ if (whenOpen) {
1602
+ button.text(whenOpen).attr("data-volcano-toggle-open", "1").attr("data-volcano-toggle-closed", text);
1603
+ button.node().parent_menu = this.dom.actionsTip.dnode;
1604
+ const escHandler = (e) => {
1605
+ if (e.key === "Escape") this.dom.actionsTip.hide();
1606
+ };
1607
+ document.addEventListener("keydown", escHandler);
1608
+ button.node().__volcanoEscHandler = escHandler;
1609
+ this.dom.actionsTip.onHide = () => {
1610
+ button.text(text).attr("data-volcano-toggle-open", null);
1611
+ button.node().parent_menu = void 0;
1612
+ document.removeEventListener("keydown", escHandler);
1613
+ button.node().__volcanoEscHandler = void 0;
1614
+ };
1615
+ } else {
1616
+ this.dom.actionsTip.onHide = void 0;
1617
+ }
1618
+ await callback();
1619
+ });
1620
+ }
1621
+ renderPlot(plotDim) {
1622
+ this.volcanoDom.svg.attr("width", plotDim.svg.width).attr("height", plotDim.svg.height);
1623
+ this.renderTermInfo(plotDim);
1624
+ this.volcanoDom.yAxisLabel.attr(
1625
+ "transform",
1626
+ `translate(${plotDim.yAxisLabel.x}, ${plotDim.yAxisLabel.y}) rotate(-90)`
1627
+ );
1628
+ this.setSvgSubscriptLabel(this.volcanoDom.yAxisLabel, "-log", "10", `(${this.viewData.pValueLabel})`);
1629
+ this.volcanoDom.xAxisLabel.attr("transform", `translate(${plotDim.xAxisLabel.x}, ${plotDim.xAxisLabel.y})`);
1630
+ if (this.termType === DATermTypes.JUNCTION) {
1631
+ this.volcanoDom.xAxisLabel.selectAll("*").remove();
1632
+ this.volcanoDom.xAxisLabel.text(this.viewData.deltaPsiAxisLabel || "\u0394PSI (case \u2212 control)");
1633
+ } else if (onDeltaBetaAxis(this.termType, this.settings)) {
1634
+ this.volcanoDom.xAxisLabel.selectAll("*").remove();
1635
+ this.volcanoDom.xAxisLabel.text(this.viewData.deltaBetaAxisLabel || "\u0394\u03B2 (case \u2212 control)");
1636
+ } else {
1637
+ this.volcanoDom.xAxisLabel.text(null);
1638
+ this.setSvgSubscriptLabel(this.volcanoDom.xAxisLabel, "log", "2", "(fold-change)");
1639
+ }
1640
+ this.renderScale(plotDim.xScale);
1641
+ this.renderScale(plotDim.yScale, true);
1642
+ if (this.viewData.volcanoPng) {
1643
+ this.volcanoDom.plot.append("image").attr("href", `data:image/png;base64,${this.viewData.volcanoPng}`).attr("x", plotDim.plot.x).attr("y", plotDim.plot.y).attr("width", plotDim.plot.width).attr("height", plotDim.plot.height).attr("preserveAspectRatio", "none");
1644
+ }
1645
+ }
1646
+ renderTermInfo(plotDim) {
1647
+ if (this.viewData.termInfo == void 0) return;
1648
+ this.volcanoDom.top.attr("transform", `translate(${plotDim.top.x}, ${plotDim.top.y})`);
1649
+ const y = this.viewData.termInfo.y;
1650
+ const addLabel = (term) => {
1651
+ return this.volcanoDom.top.append("text").attr("font-size", "0.9em").attr("transform", `translate(${term.x}, ${y + 10})`).text(term.label);
1652
+ };
1653
+ const firstTerm = this.viewData.termInfo.first;
1654
+ addLabel(firstTerm);
1655
+ const secondTerm = this.viewData.termInfo.second;
1656
+ const secondLabel = addLabel(secondTerm);
1657
+ secondLabel.attr("text-anchor", "end");
1658
+ }
1659
+ renderScale(scale, isLeft = false) {
1660
+ const scaleG = this.volcanoDom[isLeft ? "yAxis" : "xAxis"].append("g").attr("transform", `translate(${scale.x}, ${scale.y})`).call(isLeft ? axisLeft(scale.scale) : axisBottom(scale.scale));
1661
+ axisstyle({
1662
+ axis: scaleG,
1663
+ color: "black",
1664
+ showline: true
1665
+ });
1666
+ }
1667
+ renderFoldChangeLine(plotDim) {
1668
+ this.volcanoDom.plot.append("line").attr("stroke", "#ccc").attr("shape-rendering", "crispEdges").attr("x1", plotDim.logFoldChangeLine.x).attr("x2", plotDim.logFoldChangeLine.x).attr("y1", plotDim.logFoldChangeLine.y1).attr("y2", plotDim.logFoldChangeLine.y2);
1669
+ }
1670
+ renderStatsMenu() {
1671
+ for (const img of this.viewData.images || []) {
1672
+ this.dom.actionsTip.d.append("img").style("display", "inline-block").style("margin-left", "10px").style("margin-top", "-30px").attr("width", 450).attr("height", 450).attr("src", img.src);
1673
+ }
1674
+ const tableHolder = this.dom.actionsTip.d.append("div").style("display", this.viewData.images.length == 1 ? "inline-block" : "block").style("margin", `${this.viewData.images.length == 1 ? `40px 10px` : `0px 0px`} 0px 5px`).style("vertical-align", "top");
1675
+ const table = table2col({ holder: tableHolder });
1676
+ for (const d of this.viewData.statsData) {
1677
+ const [td1, td2] = table.addRow();
1678
+ td1.text(d.label);
1679
+ td2.style("text-align", "end").text(Number.isInteger(d.value) ? d.value.toLocaleString() : d.value);
1680
+ }
1681
+ }
1682
+ /* Where the DMRs are, along the whole genome: every kept DMR in the server's PNG, hyper above
1683
+ the line and hypo below, height = evidence; the most significant thousand are live. A dot is
1684
+ the same DMR the volcano shows, so hover and click give the volcano's own rows and actions --
1685
+ the violin of that region and the region view, a genome browser with the called DMRs, the
1686
+ per-CpG group means and the genes. Same lifecycle as the p-value table: redrawn from each
1687
+ response, never left stale. */
1688
+ /** What the scan covered, for the figure titles: the chromosome when that is all of it, and "the
1689
+ * genome" otherwise. A one-chromosome scan describing itself as genome-wide overstates every
1690
+ * number under it, which is what a dev host holding a subset of CpG shards produces. */
1691
+ scanSpan() {
1692
+ const chrs = this.viewData.scan?.chromosomes || [];
1693
+ return chrs.length == 1 ? chrs[0] : "the genome";
1694
+ }
1695
+ renderScanManhattan() {
1696
+ const { manhattan } = this.viewData.scan;
1697
+ const div = this.row.insert("div", "#sjpp-volcano-pValueTable").attr("id", "sjpp-volcano-scanManhattan").attr("data-testid", "sjpp-volcano-scanManhattan").style("display", "block").style("margin", "0 0 0 20px");
1698
+ const asRow = (d) => ({
1699
+ promoter_id: `${d.chrom}:${d.start}-${d.stop}`,
1700
+ gene_name: d.gene_name,
1701
+ chr: d.chrom,
1702
+ start: d.start,
1703
+ stop: d.stop,
1704
+ delta_beta: d.delta_beta,
1705
+ fold_change: d.fold_change,
1706
+ original_p_value: d.p,
1707
+ adjusted_p_value: d.p,
1708
+ no_cpgs: d.no_cpgs,
1709
+ excess: d.excess,
1710
+ min_smoothed_fdr: d.min_smoothed_fdr
1711
+ });
1712
+ const g2 = this.viewData.scan.matchedSamplelst?.groups?.[1]?.name || "case group";
1713
+ const link = {
1714
+ points: [],
1715
+ highlight: () => {
1716
+ },
1717
+ region: (d) => ({ chr: d.chrom, start: d.start, stop: d.stop })
1718
+ };
1719
+ const handle = plotManhattan(
1720
+ div,
1721
+ { png: manhattan.png, plotData: manhattan.plotData },
1722
+ {
1723
+ ...manhattanLayoutDefaults,
1724
+ plotWidth: manhattan.plotWidth,
1725
+ plotHeight: manhattan.plotHeight,
1726
+ // the radius the PNG was drawn at; see the profile below. Absent from older cached scans
1727
+ pngDotRadius: manhattan.dotRadius ?? manhattanLayoutDefaults.pngDotRadius,
1728
+ // the server already picked N per direction; the client must not re-cap by |y|
1729
+ interactiveDotsCap: manhattan.plotData.points.length,
1730
+ maxTooltipGenes: this.settings.maxTooltipGenes,
1731
+ legendItemWidth: 130,
1732
+ // saved from the volcano's download menu, with the profile under it
1733
+ showDownload: false
1734
+ },
1735
+ void 0,
1736
+ {
1737
+ // names the chromosome when that is all the scan covered, rather than "the genome"
1738
+ title: `DMRs along ${this.scanSpan()}, direction in ${g2} (top ${manhattan.interactive.toLocaleString()} per direction interactive)`,
1739
+ // short, because it runs down a 300 px axis: the legend and title say what the sign means
1740
+ yAxisLabel: `\xB1log\u2081\u2080(${this.viewData.pValueLabel})`,
1741
+ legend: [
1742
+ { label: "Hypermethylated", color: HYPER_COLOR, hollow: !manhattan.filled },
1743
+ { label: "Hypomethylated", color: HYPO_COLOR, hollow: !manhattan.filled }
1744
+ ],
1745
+ itemNoun: "DMR",
1746
+ renderSingleHoverTooltip: (d, container) => {
1747
+ const table = table2col({ holder: container.append("table") });
1748
+ this.addTooltipRows(asRow(d), table);
1749
+ if (d.no_cpgs != null) addTooltipRow(table, "CpGs", d.no_cpgs);
1750
+ },
1751
+ buildMultiHitTableData: (dots) => this.buildMultiHitTable(dots.map(asRow)),
1752
+ getActions: (d) => this.getActionMenuOpts(asRow(d)),
1753
+ getRowKey: (d) => `${d.chrom}:${d.start}-${d.stop}`,
1754
+ onHover: (dots) => this.mirrorHover(link, dots)
1755
+ }
1756
+ );
1757
+ this.linked.push(Object.assign(link, handle));
1758
+ this.renderMethylationProfile(this.viewData.scan.matchedSamplelst?.groups?.[0]?.name || "control group", g2);
1759
+ }
1760
+ /* The genome-wide methylation profile, under the DMR plot: mean beta per group in 100 kb bins,
1761
+ drawn as the per-bin difference. The DMR plot above shows the regions that passed a threshold;
1762
+ this shows every bin that was measured, which is what says whether the methylome shifted a
1763
+ little everywhere or a lot in a few places.
1764
+
1765
+ Same component and the same hover/click layer as the DMR plot, on the bins that moved most in
1766
+ each direction: 29,000 dots in a band cannot be read by eye, so a dot has to be able to say
1767
+ which 100 kb it is, what each group's mean beta there was, and how many CpGs that rests on.
1768
+ Clicking opens the browser on the bin -- the question a standout bin raises is which of the
1769
+ scan's DMRs are inside it, and that is the view that answers it. */
1770
+ renderMethylationProfile(controlName, caseName) {
1771
+ const profile = this.viewData.scan?.profile;
1772
+ if (!profile) return;
1773
+ const div = this.dom.holder.select("#sjpp-volcano-scanManhattan").append("div").attr("data-testid", "sjpp-volcano-methylationProfile").style("display", "block").style("margin-top", "-70px");
1774
+ const region = (d) => ({ chr: d.chrom, start: d.pos, stop: d.pos + profile.binBp });
1775
+ const label = (d) => `${d.chrom}:${(d.pos + 1).toLocaleString()}-${(d.pos + profile.binBp).toLocaleString()}`;
1776
+ const link = { points: [], highlight: () => {
1777
+ }, region };
1778
+ const handle = plotManhattan(
1779
+ div,
1780
+ { png: profile.png, plotData: profile.plotData },
1781
+ {
1782
+ ...manhattanLayoutDefaults,
1783
+ plotWidth: profile.plotWidth,
1784
+ plotHeight: profile.plotHeight,
1785
+ /* The radius the PNG was drawn at, not the shared default of 2: the hover layer is
1786
+ placed in the PNG's own pixel space, and a 1 px mismatch in the padding stretches
1787
+ the image against the dot coordinates the server computed. */
1788
+ pngDotRadius: profile.dotRadius,
1789
+ // the server already picked N per direction; the client must not re-cap by |y|
1790
+ interactiveDotsCap: profile.plotData.points.length,
1791
+ /* More rows than the volcano's 5. At 100 kb there are ~29,000 bins over 1,000 px, so
1792
+ a cursor covers a median of 7 live bins on MMRF however tight the hit radius -- the
1793
+ dots genuinely overlap at this scale. 8 shows the whole neighbourhood on a typical
1794
+ hover instead of 5 of it. */
1795
+ maxTooltipGenes: 8,
1796
+ showLegend: false,
1797
+ showDownload: false
1798
+ },
1799
+ void 0,
1800
+ {
1801
+ /* The width drawn, not the width requested: the server reports back what it binned at,
1802
+ and a reader quoting the figure needs the two to agree. The interactive count is the
1803
+ live dot count rather than the per-direction rule, because at a coarse width the rule
1804
+ reaches every bin and "top 1,000 per direction" would read as a restriction. */
1805
+ title: `${this.scanSpan() == "the genome" ? "Methylome-wide" : `${this.scanSpan()}-wide`} profile: mean \u0394\u03B2 per ${bplen(profile.binBp)} bin in ${caseName} (${profile.interactive.toLocaleString()} of ${profile.bins.toLocaleString()} bins interactive)`,
1806
+ yAxisLabel: "\u0394\u03B2 per bin",
1807
+ itemNoun: "bin",
1808
+ renderSingleHoverTooltip: (d, container) => {
1809
+ const table = table2col({ holder: container.append("table") });
1810
+ addTooltipRow(table, "Region", label(d));
1811
+ addTooltipRow(table, "\u0394\u03B2", roundValueAuto(d.y));
1812
+ addTooltipRow(table, `Mean \u03B2, ${controlName}`, roundValueAuto(d.control));
1813
+ addTooltipRow(table, `Mean \u03B2, ${caseName}`, roundValueAuto(d.case));
1814
+ addTooltipRow(table, "CpGs measured", d.n_probes.toLocaleString());
1815
+ },
1816
+ buildMultiHitTableData: (dots) => ({
1817
+ columns: [{ label: "Region" }, { label: "\u0394\u03B2", sortable: true }, { label: "CpGs", sortable: true }],
1818
+ rows: dots.map((d) => [{ value: label(d) }, { value: roundValueAuto(d.y) }, { value: d.n_probes }])
1819
+ }),
1820
+ getActions: (d) => [
1821
+ {
1822
+ label: "Genome browser",
1823
+ onClick: async () => await this.interactions.launchMethylationGenomeBrowser(region(d), this.viewData.scan)
1824
+ }
1825
+ ],
1826
+ getRowKey: (d) => label(d),
1827
+ onHover: (dots) => this.mirrorHover(link, dots)
1828
+ }
1829
+ );
1830
+ this.linked.push(Object.assign(link, handle));
1831
+ }
1832
+ /* Ring, on every other figure, the live dots overlapping what the cursor is on. Only live dots can
1833
+ be ringed -- the rest are pixels in a PNG -- so a hovered DMR outside another figure's interactive
1834
+ top N has nothing to light up there. */
1835
+ mirrorHover(src, dots) {
1836
+ const hovered = dots.map(src.region);
1837
+ for (const p of this.linked) {
1838
+ if (p === src) continue;
1839
+ p.highlight(
1840
+ hovered.length ? p.points.filter((d) => {
1841
+ const r = p.region(d);
1842
+ return hovered.some((h) => h.chr == r.chr && h.start < r.stop && r.start < h.stop);
1843
+ }) : []
1844
+ );
1845
+ }
1846
+ }
1847
+ renderPValueTable() {
1848
+ if (!this.settings.showPValueTable) return;
1849
+ const maxTableRows = 5e3;
1850
+ const allRows = this.viewData.pValueTableData.rows;
1851
+ const rows = allRows.length > maxTableRows ? allRows.slice(0, maxTableRows) : allRows;
1852
+ if (allRows.length > maxTableRows) {
1853
+ this.volcanoDom.pValueTable.append("div").style("padding", "5px 10px").style("font-size", ".8em").style("color", "#666").text(
1854
+ `Showing top ${maxTableRows.toLocaleString()} of ${allRows.length.toLocaleString()} significant results (sorted by fold-change)`
1855
+ );
1856
+ }
1857
+ renderTable({
1858
+ columns: this.viewData.pValueTableData.columns,
1859
+ rows,
1860
+ div: this.volcanoDom.pValueTable,
1861
+ showLines: true,
1862
+ maxHeight: `${this.viewData.pValueTableData.height}px`,
1863
+ resize: true,
1864
+ header: { allowSort: true },
1865
+ noRadioBtn: true,
1866
+ noButtonCallback: (i) => {
1867
+ const key = this.viewData.pValueTableData.rowKeys.get(rows[i]);
1868
+ if (!key) return;
1869
+ this.interactions.highlightDataPoint(key);
1870
+ },
1871
+ hoverEffects: (tr, row) => {
1872
+ const circles = this.volcanoDom.plot.selectAll("circle").nodes();
1873
+ const key = this.viewData.pValueTableData.rowKeys.get(row);
1874
+ const dataKey = this.termType === DATermTypes.DNA_METHYLATION ? "promoter_id" : "gene_name";
1875
+ const circle = circles.find((d) => d.__data__[dataKey] == key);
1876
+ if (!circle || circle.__data__.highlighted) return;
1877
+ let clone;
1878
+ tr.on("mouseover", () => {
1879
+ if (circle.__data__.highlighted || clone) return;
1880
+ clone = this.volcanoDom.plot.node()?.appendChild(circle.cloneNode(true));
1881
+ clone.setAttribute("fill-opacity", 0.9);
1882
+ });
1883
+ tr.on("mouseleave", () => {
1884
+ if (!clone) return;
1885
+ clone.remove();
1886
+ clone = null;
1887
+ });
1888
+ this.volcanoDom.pValueTable.on("mouseover", () => {
1889
+ selectAll_default(circles).attr("stroke-opacity", 0.075);
1890
+ });
1891
+ this.volcanoDom.pValueTable.on("mouseleave", () => {
1892
+ selectAll_default(circles).attr("stroke-opacity", (d) => d.significant ? 0.35 : 0.2);
1893
+ });
1894
+ }
1895
+ });
1896
+ }
1897
+ setSvgSubscriptLabel(textElem, prefix, subscript, suffix) {
1898
+ textElem.text(null);
1899
+ textElem.append("tspan").text(prefix);
1900
+ textElem.append("tspan").attr("baseline-shift", "sub").attr("font-size", "0.7em").text(subscript);
1901
+ textElem.append("tspan").text(suffix);
1902
+ }
1903
+ attachInteractions(plotDim) {
1904
+ const points = this.viewData.pointData;
1905
+ if (!points || points.length === 0) return;
1906
+ const dotRadiusPx = this.viewData.plotExtent.dotRadiusPx;
1907
+ const hitRadius = dotRadiusPx + 3;
1908
+ const highlightRadius = Math.max(0.5, dotRadiusPx - 0.5);
1909
+ const highlightColor = this.settings.defaultHighlightColor;
1910
+ const hoverLayer = this.volcanoDom.plot.append("g").attr("id", "sjpp-volcano-hover").style("pointer-events", "none");
1911
+ const cover = this.volcanoDom.plot.append("rect").attr("id", "sjpp-volcano-cover").attr("x", plotDim.plot.x).attr("y", plotDim.plot.y).attr("width", plotDim.plot.width).attr("height", plotDim.plot.height).attr("fill", "transparent").style("pointer-events", "all").style("cursor", "default");
1912
+ const circlePath = (r) => `M${r},0 A${r},${r} 0 1,1 ${-r},0 A${r},${r} 0 1,1 ${r},0 Z`;
1913
+ const link = this.viewData.scan ? {
1914
+ points,
1915
+ region: (d) => ({ chr: d.chr, start: d.start, stop: d.stop }),
1916
+ highlight: (dots) => {
1917
+ drawHoverShapes(
1918
+ linkedLayer,
1919
+ dots.map((d) => ({
1920
+ path: circlePath(dotRadiusPx + 2),
1921
+ transform: `translate(${d.x},${d.y})`,
1922
+ stroke: "black",
1923
+ strokeWidth: 2
1924
+ }))
1925
+ );
1926
+ }
1927
+ } : void 0;
1928
+ const linkedLayer = this.volcanoDom.plot.append("g").style("pointer-events", "none");
1929
+ if (link) this.linked.push(link);
1930
+ new DataPointInteractions({
1931
+ cover,
1932
+ hoverLayer,
1933
+ hoverTip: this.dom.tip,
1934
+ points,
1935
+ // Quadtree in cover-local space — d.x/d.y are SVG-absolute, so subtract
1936
+ // the plot rect's origin once when building the tree.
1937
+ getX: (d) => d.x - plotDim.plot.x,
1938
+ getY: (d) => d.y - plotDim.plot.y,
1939
+ hitRadius,
1940
+ toHoverSpec: (d) => ({
1941
+ path: circlePath(highlightRadius),
1942
+ // Hover layer lives in the same coord space as the dots (SVG-absolute),
1943
+ // so translate by d.x/d.y — NOT the cover-local pair.
1944
+ transform: `translate(${d.x},${d.y})`,
1945
+ fill: highlightColor,
1946
+ fillOpacity: 0.9,
1947
+ stroke: "none"
1948
+ }),
1949
+ maxTooltipRows: this.settings.maxTooltipGenes,
1950
+ ...link ? { onHover: (dots) => this.mirrorHover(link, dots) } : {},
1951
+ itemNoun: "gene",
1952
+ renderSingleHoverTooltip: (d, container) => {
1953
+ const table = table2col({ holder: container.append("table") });
1954
+ this.addTooltipRows(d, table);
1955
+ },
1956
+ buildMultiHitTableData: (dots) => this.buildMultiHitTable(dots),
1957
+ getActions: (d) => this.getActionMenuOpts(d),
1958
+ renderSingleHitInfo: (d, container) => {
1959
+ const tbl = table2col({ holder: container.append("table") });
1960
+ this.addTooltipRows(d, tbl);
1961
+ },
1962
+ getRowKey: (d) => d.gene_name
1963
+ }).attach();
1964
+ }
1965
+ /** Multi-hit hover table for differential splicing: one row per intron cluster. */
1966
+ get onDeltaBeta() {
1967
+ return onDeltaBetaAxis(this.termType, this.settings);
1968
+ }
1969
+ buildSpliceMultiHitTable(dots) {
1970
+ const { pValueLabel, singlePValue } = this.viewData;
1971
+ const pLabel = pValueLabel.charAt(0).toUpperCase() + pValueLabel.slice(1);
1972
+ const pField = singlePValue ? "original_p_value" : `${this.settings.pValueType}_p_value`;
1973
+ const columns = [
1974
+ { label: "Cluster" },
1975
+ { label: "Gene(s)" },
1976
+ { label: "\u0394PSI", sortable: true },
1977
+ { label: pLabel, sortable: true }
1978
+ ];
1979
+ const rows = dots.map((d) => [
1980
+ { value: d.cluster_id },
1981
+ { value: d.genes || "" },
1982
+ { value: roundValueAuto(d.delta_psi) },
1983
+ { value: roundValueAuto(d[pField]) }
1984
+ ]);
1985
+ return { columns, rows };
1986
+ }
1987
+ // p-value rows duplicate those in addTooltipRows
1988
+ addSpliceTooltipRows(d, table) {
1989
+ const c = d;
1990
+ addTooltipRow(table, "Cluster", c.cluster_id);
1991
+ if (c.genes) addTooltipRow(table, "Gene(s)", c.genes);
1992
+ if (c.chr) addTooltipRow(table, "Position", `${c.chr}:${c.start}-${c.stop}`);
1993
+ addTooltipRow(table, "\u0394PSI", roundValueAuto(c.delta_psi));
1994
+ if (c.psi_control != null) addTooltipRow(table, "PSI (group 1)", roundValueAuto(c.psi_control));
1995
+ if (c.psi_case != null) addTooltipRow(table, "PSI (group 2)", roundValueAuto(c.psi_case));
1996
+ if (c.n_junc != null) addTooltipRow(table, "Junctions", c.n_junc);
1997
+ if (c.top_intron) addTooltipRow(table, "Top intron", c.top_intron);
1998
+ if (this.viewData.singlePValue) {
1999
+ addTooltipRow(table, this.viewData.pValueLabel, roundValueAuto(d.original_p_value));
2000
+ } else {
2001
+ addTooltipRow(table, "Original p-value", roundValueAuto(d.original_p_value));
2002
+ if (d.adjusted_p_value != void 0) addTooltipRow(table, "Adjusted p-value", roundValueAuto(d.adjusted_p_value));
2003
+ }
2004
+ }
2005
+ buildMultiHitTable(dots) {
2006
+ if (this.termType === DATermTypes.JUNCTION) return this.buildSpliceMultiHitTable(dots);
2007
+ const isDM = this.termType === DATermTypes.DNA_METHYLATION;
2008
+ const isDAP = this.termType === DATermTypes.PROTEOME_DAP;
2009
+ const effectLabel = this.onDeltaBeta ? "\u0394\u03B2" : "log\u2082(FC)";
2010
+ const pValueType = this.settings.pValueType;
2011
+ const { pValueLabel, singlePValue } = this.viewData;
2012
+ const pLabel = pValueLabel.charAt(0).toUpperCase() + pValueLabel.slice(1);
2013
+ const pField = singlePValue ? "original_p_value" : `${pValueType}_p_value`;
2014
+ const columns = isDM ? [
2015
+ { label: elementNoun(this.settings?.elementType).one },
2016
+ { label: "Gene(s)" },
2017
+ { label: effectLabel, sortable: true },
2018
+ { label: pLabel, sortable: true }
2019
+ ] : isDAP ? [
2020
+ { label: "Identifier" },
2021
+ { label: "Gene" },
2022
+ { label: effectLabel, sortable: true },
2023
+ { label: pLabel, sortable: true }
2024
+ ] : [{ label: "Gene" }, { label: effectLabel, sortable: true }, { label: pLabel, sortable: true }];
2025
+ const rows = dots.map((d) => {
2026
+ const fc = { value: roundValueAuto(this.onDeltaBeta ? d.delta_beta : d.fold_change) };
2027
+ const pval = { value: roundValueAuto(d[pField]) };
2028
+ if (isDM) {
2029
+ return [{ value: formatPromoterLabel(d) }, { value: d.gene_name || "" }, fc, pval];
2030
+ }
2031
+ if (isDAP) {
2032
+ return [{ value: d.gene_name || "" }, { value: d.gene || "" }, fc, pval];
2033
+ }
2034
+ return [{ value: d.gene_name || "" }, fc, pval];
2035
+ });
2036
+ return { columns, rows };
2037
+ }
2038
+ /** Per-data-point action menu items (Violin / DMR / Box-plot). Used by
2039
+ * both the single-gene click flow and the multi-gene click-menu rows so
2040
+ * the launchers stay in lock-step. */
2041
+ getActionMenuOpts(d) {
2042
+ const termType = this.termType;
2043
+ const interactions = this.interactions;
2044
+ const all = [
2045
+ {
2046
+ label: "Violin plot",
2047
+ isVisible: () => termType === DATermTypes.DNA_METHYLATION || termType === DATermTypes.GENE_EXPRESSION,
2048
+ onClick: async () => {
2049
+ if (termType === DATermTypes.DNA_METHYLATION) interactions.launchDNAMethViolin(d);
2050
+ if (termType === DATermTypes.GENE_EXPRESSION) interactions.launchViolinGeneExp(d.gene_name);
2051
+ }
2052
+ },
2053
+ {
2054
+ /* A scan has already called every DMR: the browser shows them from the cache, beside
2055
+ the genes and cCREs, with no per-CpG detail; the region view below adds that detail. An
2056
+ element-class hit (promoter, cCRE) opens on the genes and cCREs around it. */
2057
+ label: "Genome browser",
2058
+ isVisible: () => termType === DATermTypes.DNA_METHYLATION,
2059
+ onClick: async () => {
2060
+ const dm = d;
2061
+ await interactions.launchMethylationGenomeBrowser(dm, this.viewData.scan);
2062
+ }
2063
+ },
2064
+ {
2065
+ label: "Genome browser",
2066
+ isVisible: () => termType === DATermTypes.JUNCTION,
2067
+ onClick: async () => {
2068
+ await interactions.launchSpliceGenomeBrowser(d);
2069
+ }
2070
+ },
2071
+ {
2072
+ /* The region view on a scan's DMR only. An element-class hit (promoter, cCRE) comes from a
2073
+ per-element test; the region view draws DMRcate's de novo calls, which need not agree with it,
2074
+ and showing one under the other mixes two analyses. The violin and the browser above serve
2075
+ elements. */
2076
+ label: "Differentially Methylated Region (DMR) Analysis",
2077
+ isVisible: () => termType === DATermTypes.DNA_METHYLATION && !!this.viewData.scan,
2078
+ onClick: async () => {
2079
+ const dm = d;
2080
+ await interactions.launchDmr({ chr: dm.chr, start: dm.start, stop: dm.stop }, this.viewData.scan);
2081
+ }
2082
+ },
2083
+ {
2084
+ label: "Box plot",
2085
+ isVisible: () => termType === DATermTypes.GENE_EXPRESSION,
2086
+ onClick: async () => {
2087
+ interactions.launchBoxPlot(d.gene_name);
2088
+ }
2089
+ }
2090
+ ];
2091
+ return all.filter((o) => o.isVisible()).map(({ label, onClick }) => ({ label, onClick }));
2092
+ }
2093
+ /** Populates a `table2col` instance with the standard volcano hover rows
2094
+ * (gene/promoter, fold-change, original + adjusted p-values). */
2095
+ addTooltipRows(d, table) {
2096
+ if (this.termType === DATermTypes.JUNCTION) {
2097
+ this.addSpliceTooltipRows(d, table);
2098
+ return;
2099
+ }
2100
+ if (this.termType === DATermTypes.DNA_METHYLATION) {
2101
+ if ("promoter_id" in d)
2102
+ addTooltipRow(table, elementNoun(this.settings?.elementType).one, formatPromoterLabel(d));
2103
+ if (d.gene_name) addTooltipRow(table, "Gene(s)", d.gene_name);
2104
+ } else if (this.termType === DATermTypes.PROTEOME_DAP) {
2105
+ addTooltipRow(table, "Identifier", d.gene_name);
2106
+ if ("gene" in d) addTooltipRow(table, "Gene", d.gene);
2107
+ } else {
2108
+ addTooltipRow(table, "Gene name", d.gene_name);
2109
+ }
2110
+ if (this.onDeltaBeta) {
2111
+ addTooltipRow(table, "\u0394\u03B2", roundValueAuto(d.delta_beta));
2112
+ } else {
2113
+ addTooltipRow(table, "log<sub>2</sub>(fold-change)", roundValueAuto(d.fold_change));
2114
+ }
2115
+ if (this.viewData.singlePValue) {
2116
+ addTooltipRow(table, this.viewData.pValueLabel, roundValueAuto(d.original_p_value));
2117
+ const sfdr = d.min_smoothed_fdr;
2118
+ if (sfdr != null && (this.viewData.scan?.yAxis ?? "min_smoothed_fdr") != "min_smoothed_fdr")
2119
+ addTooltipRow(table, "Min smoothed FDR", roundValueAuto(sfdr));
2120
+ } else {
2121
+ addTooltipRow(table, "Original p-value", roundValueAuto(d.original_p_value));
2122
+ if (d.adjusted_p_value != void 0) addTooltipRow(table, "Adjusted p-value", roundValueAuto(d.adjusted_p_value));
2123
+ }
2124
+ }
2125
+ };
2126
+ function addTooltipRow(table, text, value) {
2127
+ const [td1, td2] = table.addRow();
2128
+ td1.html(text);
2129
+ td2.text(value);
2130
+ }
2131
+ function renderDataPoints(self) {
2132
+ self.volcanoDom.plot.selectAll("circle").data(self.viewData.pointData).enter().append("circle").attr("stroke", (d) => rgb(d.color).formatHex()).attr("stroke-opacity", (d) => d.significant ? 0.35 : 0.2).attr("stroke-width", 1).attr("fill", self.settings.defaultHighlightColor).attr("fill-opacity", (d) => d.highlighted ? 0.9 : 0).attr("cx", (d) => d.x).attr("cy", (d) => d.y).attr("r", (d) => d.radius).style("pointer-events", "none");
2133
+ }
2134
+
2135
+ // plots/volcano/VolcanoControlInputs.ts
2136
+ var isScan = (plot) => plot?.settings?.volcano?.elementType == DMR_SCAN_ELEMENT_TYPE;
2137
+ var VolcanoControlInputs = class {
2138
+ constructor(config, termType, elementTypes, chromosomes) {
2139
+ this.config = config;
2140
+ this.termType = termType;
2141
+ this.elementTypes = elementTypes || [];
2142
+ this.chromosomes = chromosomes || [];
2143
+ this.inputs = [
2144
+ {
2145
+ // DAP volcanoes threshold a single FDR (adjusted p-value); other term types
2146
+ // threshold a p-value.
2147
+ label: this.config.termType == PROTEOME_DAP ? "FDR significance (-log\u2081\u2080)" : "P value significance (-log\u2081\u2080)",
2148
+ type: "number",
2149
+ chartType: "volcano",
2150
+ settingsKey: "pValue",
2151
+ title: this.config.termType == PROTEOME_DAP ? "The FDR threshold to determine statistical significance" : "The p-value threshold to determine statistical significance",
2152
+ min: 0,
2153
+ // 5e-324 is the smallest positive number greater than 0 representable
2154
+ // in IEEE 64-bit floating point (i.e. javascripts native Number.MIN_VALUE)
2155
+ // -Math.log10(5e-324) = 323.3
2156
+ max: 323.3,
2157
+ step: 1
2158
+ },
2159
+ {
2160
+ label: "P value",
2161
+ type: "radio",
2162
+ chartType: "volcano",
2163
+ settingsKey: "pValueType",
2164
+ title: "Toggle between original and adjusted pvalues for volcano plot",
2165
+ // DAP files carry only a single FDR, and a DMR scan a single p, so there is nothing to
2166
+ // toggle between
2167
+ getDisplayStyle: (plot) => this.config.termType == PROTEOME_DAP || isScan(plot) ? "none" : "",
2168
+ options: [
2169
+ { label: "Adjusted", value: "adjusted" },
2170
+ { label: "Original", value: "original" }
2171
+ ]
2172
+ },
2173
+ /* Hidden for differential methylation: a DM run plots and thresholds on delta-beta,
2174
+ so a log2 cutoff would set a limit in units the plot never shows. Every other term
2175
+ type still gets it.
2176
+ Splicing is hidden for the same reason -- it plots and thresholds on delta-PSI, and
2177
+ supplies its own |dPSI| control in addSplicingControlInputs(). */
2178
+ ...this.termType === DNA_METHYLATION || this.termType === JUNCTION ? [] : [
2179
+ {
2180
+ label: "Fold change (log\u2082)",
2181
+ type: "number",
2182
+ chartType: "volcano",
2183
+ settingsKey: "foldChangeCutoff",
2184
+ title: "The fold change threshold to determine biological significance",
2185
+ min: -10,
2186
+ max: 10
2187
+ }
2188
+ ],
2189
+ {
2190
+ label: "Max interactive dots",
2191
+ type: "number",
2192
+ chartType: "volcano",
2193
+ settingsKey: "maxInteractiveDots",
2194
+ title: "Cap on the number of top-significant points the server returns as interactive overlay circles. The PNG still shows every dot.",
2195
+ min: 0,
2196
+ max: 2e4,
2197
+ step: 100
2198
+ },
2199
+ //Preferably, keep all the display (e.g. colors, sizes, etc.) controls
2200
+ //at the bottom of the list or at least together
2201
+ {
2202
+ label: "Plot height",
2203
+ type: "number",
2204
+ chartType: "volcano",
2205
+ settingsKey: "height",
2206
+ title: "Height of the plot in pixels",
2207
+ min: 300,
2208
+ max: 1e3
2209
+ },
2210
+ {
2211
+ label: "Plot width",
2212
+ type: "number",
2213
+ chartType: "volcano",
2214
+ settingsKey: "width",
2215
+ title: "Width of the plot in pixels",
2216
+ min: 300,
2217
+ max: 1e3
2218
+ },
2219
+ {
2220
+ label: "Significant value color",
2221
+ type: "color",
2222
+ chartType: "volcano",
2223
+ title: "Default color for significant data points.",
2224
+ settingsKey: "defaultSignColor",
2225
+ getDisplayStyle: () => {
2226
+ if (this.config.termType == SINGLECELL_CELLTYPE) return "none";
2227
+ const controlColor = this.config.tw?.term?.values?.[this.config.samplelst.groups[0].name]?.color;
2228
+ const caseColor = this.config.tw?.term?.values?.[this.config.samplelst.groups[1].name].color;
2229
+ if (controlColor && caseColor) return "none";
2230
+ else return "";
2231
+ }
2232
+ },
2233
+ {
2234
+ label: "Non-significant value color",
2235
+ type: "color",
2236
+ chartType: "volcano",
2237
+ title: "Default color for non-significant data points.",
2238
+ settingsKey: "defaultNonSignColor"
2239
+ },
2240
+ {
2241
+ label: "Highlight color",
2242
+ type: "color",
2243
+ chartType: "volcano",
2244
+ title: "Default color for highlighted data points.",
2245
+ settingsKey: "defaultHighlightColor"
2246
+ }
2247
+ ];
2248
+ this.setVolcanoControlInputs();
2249
+ }
2250
+ /** Add more term type specific controls here. */
2251
+ setVolcanoControlInputs() {
2252
+ this.addGeneExpControlInputs();
2253
+ this.addDNAMethControlInputs();
2254
+ this.addSplicingControlInputs();
2255
+ this.addSingleCellCTControlInputs();
2256
+ }
2257
+ addGeneExpControlInputs() {
2258
+ if (this.termType !== GENE_EXPRESSION) return;
2259
+ const geInputs = [
2260
+ {
2261
+ label: "Minimum read count",
2262
+ type: "number",
2263
+ chartType: "volcano",
2264
+ settingsKey: "minCount",
2265
+ title: "The smallest number of reads required for a gene to be considered in the analysis",
2266
+ min: 0,
2267
+ max: 1e4
2268
+ },
2269
+ {
2270
+ label: "Minimum total read count",
2271
+ type: "number",
2272
+ chartType: "volcano",
2273
+ settingsKey: "minTotalCount",
2274
+ title: "The smallest total number of reads required for a gene to be considered in the analysis",
2275
+ min: 0,
2276
+ max: 1e4
2277
+ },
2278
+ {
2279
+ label: "CPM cutoff",
2280
+ type: "number",
2281
+ chartType: "volcano",
2282
+ settingsKey: "cpmCutoff",
2283
+ title: "The minimum normalized expression threshold to retain only genes with sufficient expression",
2284
+ min: 0
2285
+ },
2286
+ {
2287
+ label: "Method",
2288
+ type: "radio",
2289
+ chartType: "volcano",
2290
+ settingsKey: "method",
2291
+ title: "Toggle between analysis methods",
2292
+ options: this.getMethodOptions()
2293
+ }
2294
+ // {
2295
+ // label: 'Rank Genes by',
2296
+ // type: 'radio',
2297
+ // chartType: 'volcano',
2298
+ // settingsKey: 'rankBy',
2299
+ // title: 'Rank genes by either the absolute value of the fold change or the variance',
2300
+ // options: [
2301
+ // { label: 'abs(Fold Change)', value: 'abs(foldChange)' },
2302
+ // { label: 'Variance', value: 'variance' }
2303
+ // ],
2304
+ // //TODO: will enable this feature when there is backhand support
2305
+ // getDisplayStyle: () => 'none'
2306
+ // }
2307
+ ];
2308
+ this.inputs.splice(0, 0, ...geInputs);
2309
+ }
2310
+ addDNAMethControlInputs() {
2311
+ if (this.termType !== DNA_METHYLATION) return;
2312
+ const scanOnly = (plot) => isScan(plot) ? "" : "none";
2313
+ const notScan = (plot) => isScan(plot) ? "none" : "";
2314
+ const dmInputs = [
2315
+ /* Element class comes FIRST because it is categorically different from the
2316
+ controls below it: those tune how the test is run, this one changes what is
2317
+ being tested. Promoters, eQTM blocks, and cCRE classes are different genomic
2318
+ features with different coordinates and different test counts, so switching
2319
+ produces a different analysis rather than a refined one.
2320
+
2321
+ Hidden unless the dataset offers a genuine choice -- a single class means
2322
+ there is nothing to pick, and a dataset using the legacy promoter-only config
2323
+ gets no new UI at all. */
2324
+ ...this.elementTypes.length > 1 ? [
2325
+ {
2326
+ label: "Element class",
2327
+ type: "dropdown",
2328
+ chartType: "volcano",
2329
+ settingsKey: "elementType",
2330
+ options: this.elementTypes.map((e) => ({ value: e.key, label: e.label })),
2331
+ title: "Which regulatory elements to test. This changes the features being analysed, not just the thresholds: promoters are TSS windows (-1500/+500 bp, the 450K array definition), cCRE promoters are the ~349 bp ENCODE promoter-like elements (the CpG-island core, no shores), eQTM blocks are runs of CpGs whose methylation correlates with a gene, and the other cCRE classes are ENCODE enhancer and CTCF annotations. Hit counts are not comparable across classes because the number of tests and the genes covered both differ. Narrow elements recover focal signal that a wide window averages away; wide windows do better on broad marks."
2332
+ }
2333
+ ] : [],
2334
+ /* The scan's own knobs, shown only while the scan is the selected class. The chromosome
2335
+ picker is a plain dropdown rather than the region search box: string2pos() turns a bare
2336
+ "chr20" into a 20kb window at the chromosome midpoint, which would silently scan 0.005% of
2337
+ the target. chrM is left out -- 16.5 kb of circular DNA that cannot carry a domain. */
2338
+ {
2339
+ label: "Scan",
2340
+ type: "dropdown",
2341
+ chartType: "volcano",
2342
+ settingsKey: "scanChromosome",
2343
+ getDisplayStyle: scanOnly,
2344
+ options: [
2345
+ { value: "", label: "Whole genome" },
2346
+ ...this.chromosomes.filter((c) => c != "chrM" && c != "chrMT").map((c) => ({ value: c, label: c }))
2347
+ ],
2348
+ title: "Show the DMRs called de novo across the whole genome, or only those on one chromosome. DMRs are always called over the whole genome, because DMRcate calibrates its cutoff over every CpG tested: one chromosome run alone calls different DMRs. The first scan of a comparison can take a minute or more on a large cohort, longer with the background drift correction; it is cached, so switching chromosomes after that is quick."
2349
+ },
2350
+ {
2351
+ label: "Correct for background drift",
2352
+ type: "checkbox",
2353
+ chartType: "volcano",
2354
+ settingsKey: "backgroundCorrection",
2355
+ boxLabel: "",
2356
+ getDisplayStyle: scanOnly,
2357
+ title: BACKGROUND_CORRECTION_TITLE
2358
+ },
2359
+ {
2360
+ label: "Y axis",
2361
+ type: "radio",
2362
+ chartType: "volcano",
2363
+ settingsKey: "scanYAxis",
2364
+ title: "Which region statistic the volcano and the DMR plot put on the y axis. DMRcate calls DMRs with the min smoothed FDR; it reports the other three for each DMR. Hover over an option for what it measures.",
2365
+ // the background correction plots its own p, so there is nothing to choose then
2366
+ getDisplayStyle: (plot) => isScan(plot) && !plot.settings.volcano.backgroundCorrection ? "" : "none",
2367
+ options: SCAN_Y_AXIS_OPTIONS
2368
+ },
2369
+ {
2370
+ label: "Min CpGs per DMR",
2371
+ type: "number",
2372
+ chartType: "volcano",
2373
+ settingsKey: "minCpgs",
2374
+ getDisplayStyle: scanOnly,
2375
+ min: 1,
2376
+ max: 1e3,
2377
+ title: "Drop DMRs called from fewer CpGs. DMRs of only two or three CpGs tend to carry the largest effect sizes but the least reliable direction, so a \u0394\u03B2-sorted table would lead with the rows that mean least. Applied to the cached scan, so changing it redraws rather than refits."
2378
+ },
2379
+ /* DMRcate's region-shape knobs. Unlike the CpG floor these change the fit's output, so each
2380
+ one refits the scan (and gets its own cache entry). */
2381
+ {
2382
+ label: "DMR bandwidth \u03BB (bp)",
2383
+ type: "number",
2384
+ chartType: "volcano",
2385
+ settingsKey: "lambda",
2386
+ getDisplayStyle: scanOnly,
2387
+ min: 50,
2388
+ max: 1e5,
2389
+ step: 50,
2390
+ title: "DMRcate lambda. Two things at once: the width of the Gaussian kernel that smooths per-CpG statistics along the genome, and the largest gap allowed between significant CpGs chained into one DMR. Larger values merge nearby signal into fewer, wider DMRs and recover broad domains; smaller values split them into narrow, focal regions. DMRcate recommends 1000 bp for CpG-resolution data. Changing it refits the scan."
2391
+ },
2392
+ {
2393
+ label: "DMR kernel scaling C",
2394
+ type: "number",
2395
+ chartType: "volcano",
2396
+ settingsKey: "C",
2397
+ getDisplayStyle: scanOnly,
2398
+ min: 0.5,
2399
+ max: 50,
2400
+ step: 0.5,
2401
+ title: "DMRcate C: the kernel standard deviation is lambda / C. A larger C gives a narrower kernel, so each CpG borrows evidence from fewer neighbours: sharper boundaries and more, smaller DMRs, at the cost of power in sparse regions. A smaller C smooths further. DMRcate recommends 2. Changing it refits the scan."
2402
+ },
2403
+ {
2404
+ label: "Per-CpG FDR cutoff",
2405
+ type: "number",
2406
+ chartType: "volcano",
2407
+ settingsKey: "fdrCutoff",
2408
+ getDisplayStyle: scanOnly,
2409
+ min: 1e-4,
2410
+ max: 0.5,
2411
+ step: 0.01,
2412
+ title: "The FDR a CpG's smoothed statistic must pass to take part in a DMR. Raising it lets weaker CpGs join, which extends DMRs and bridges gaps between them; lowering it keeps only the strongest CpGs, giving shorter, fewer DMRs. DMRcate's default is 0.05. This is not the volcano's significance threshold, which is applied afterwards to each DMR. Changing it refits the scan."
2413
+ },
2414
+ {
2415
+ /* Display width for the methylome-wide profile only. The metric is the 100 kb bin and
2416
+ the Statistics rows stay on it whatever this says -- this is here because 29,000 dots
2417
+ over 1,000 px overlap however small the dot, so the native figure reads as a band. */
2418
+ label: "Profile bin width",
2419
+ type: "dropdown",
2420
+ chartType: "volcano",
2421
+ settingsKey: "profileBinBp",
2422
+ getDisplayStyle: scanOnly,
2423
+ options: [
2424
+ { value: 1e5, label: "100 Kb (native)" },
2425
+ { value: 5e5, label: "500 Kb" },
2426
+ { value: 1e6, label: "1 Mb" },
2427
+ { value: 5e6, label: "5 Mb" }
2428
+ ],
2429
+ // a <select> hands back its value as a string; the setting is a width in bp
2430
+ processInput: (v) => Number(v),
2431
+ title: "How wide a bin the methylome-wide profile draws. 100 kb is the width the metric is computed and reported at (Zhou 2018); the coarser widths average neighbouring bins into one dot, weighted by the CpGs each rests on, so a genome-wide shift is legible instead of hidden in a band of overlapping dots. Display only: the Statistics rows and the fraction-of-bins-moved figures stay on the 100 kb bins, and changing this redraws the cached scan rather than refitting it. The most extreme 1,000 bins per direction stay hoverable at any width."
2432
+ },
2433
+ {
2434
+ label: "Min samples per group",
2435
+ type: "number",
2436
+ chartType: "volcano",
2437
+ settingsKey: "minSamplesPerGroup",
2438
+ title: "Minimum non-NA samples required per group for a promoter to be tested",
2439
+ // the scan resolves its own groups (3+ per group, fixed) and has no per-element NA filter
2440
+ getDisplayStyle: notScan,
2441
+ min: 1,
2442
+ max: 100
2443
+ },
2444
+ {
2445
+ label: "Exclude sex chromosomes",
2446
+ type: "checkbox",
2447
+ chartType: "volcano",
2448
+ settingsKey: "excludeSexChr",
2449
+ boxLabel: "",
2450
+ // the scan honours it too: scanChromosomes() drops chrX/chrY from a whole-genome scan
2451
+ title: "Drop chrX and chrY (promoters, elements, or whole chromosomes from a DMR scan). Recommended for mixed-sex cohorts \u2014 X-inactivation makes chrX methylation strongly sex-dependent, so a sex-imbalanced comparison reports sex rather than the grouping variable. On a scan this also shifts the autosomal DMRs slightly, since the DMRcate prior and its multiple-testing corrections are genome-wide; gene links and gene set enrichment lose the X-linked genes."
2452
+ },
2453
+ {
2454
+ label: "Center \u0394\u03B2 on median",
2455
+ type: "checkbox",
2456
+ chartType: "volcano",
2457
+ settingsKey: "centerDeltaBeta",
2458
+ boxLabel: "",
2459
+ // the background correction is the scan's version of this question
2460
+ getDisplayStyle: notScan,
2461
+ title: 'Move the \u0394\u03B2 origin to the median across all tested elements, so 0 is the typical element rather than no change. Use it to ask "which elements moved MORE than the typical one" \u2014 at a symmetric cutoff, a contrast whose whole distribution sits off zero clears the hyper threshold more easily than the hypo one, which skews the hyper:hypo ratio on its own. Leave it off to ask "which elements gained or lost methylation", since a genuine genome-wide shift is itself a result and centering would subtract it. The \u0394\u03B2 values in the table and its download are unaffected either way.'
2462
+ },
2463
+ {
2464
+ label: "Min \u0394\u03B2",
2465
+ type: "number",
2466
+ chartType: "volcano",
2467
+ settingsKey: "deltaBetaCutoff",
2468
+ title: "Effect-size cutoff for differential methylation, applied to \u0394\u03B2. 0.1 is a 10-percentage-point change in methylation, the conventional floor for calling a region differentially methylated. Kept separate from the log\u2082 cutoff because the two are not interchangeable.",
2469
+ min: 0,
2470
+ max: 1,
2471
+ step: 0.01
2472
+ }
2473
+ ];
2474
+ this.inputs.splice(0, 0, ...dmInputs);
2475
+ }
2476
+ addSingleCellCTControlInputs() {
2477
+ if (this.termType !== SINGLECELL_CELLTYPE) return;
2478
+ const scctInputs = [];
2479
+ this.inputs.splice(0, 0, ...scctInputs);
2480
+ }
2481
+ addSplicingControlInputs() {
2482
+ if (this.termType !== JUNCTION) return;
2483
+ const dsInputs = [
2484
+ {
2485
+ label: "Method",
2486
+ type: "radio",
2487
+ chartType: "volcano",
2488
+ settingsKey: "method",
2489
+ title: "Which engine computes the test",
2490
+ options: this.getSpliceMethodOptions()
2491
+ },
2492
+ {
2493
+ label: "Minimum counts per cluster",
2494
+ type: "number",
2495
+ chartType: "volcano",
2496
+ settingsKey: "minCountsPerCluster",
2497
+ title: "Threshold on each sample's total read count in the cluster",
2498
+ min: 0,
2499
+ max: 1e4
2500
+ },
2501
+ {
2502
+ /* leafcutter's -i: an intron must be seen in at least this many samples. Defaulted by
2503
+ validateDSSettings to a fraction of cohort size rather than a fixed count, because a
2504
+ fixed one silently loosens as N grows -- 5 samples is a third of a 15-sample run and
2505
+ 0.2% of a 2,500-sample one. Editable here so a user can override that default. */
2506
+ label: "Minimum samples per intron",
2507
+ type: "number",
2508
+ chartType: "volcano",
2509
+ settingsKey: "minSamplesPerIntron",
2510
+ title: "An intron must be observed in at least this many samples to be kept. Defaults to 2% of the cohort, floor 5.",
2511
+ min: 1,
2512
+ max: 1e4
2513
+ },
2514
+ {
2515
+ // leafcutter's -g: the same floor, applied within each of the two groups
2516
+ label: "Minimum samples per group",
2517
+ type: "number",
2518
+ chartType: "volcano",
2519
+ settingsKey: "minSamplesPerGroup",
2520
+ title: "A cluster must have sufficient coverage in at least this many samples in EACH group. Defaults to 1% of the cohort, floor 3.",
2521
+ min: 1,
2522
+ max: 1e4
2523
+ },
2524
+ {
2525
+ /* The cutoff that actually matters for this term type. At large cohorts the p-value
2526
+ stops discriminating -- at ~1000 per group most "significant" clusters shift under a
2527
+ percentage point of PSI -- so the effect size is the filter, not the p. The unit is
2528
+ named in the title because 0.05 here is 5 percentage points, not a p-value. */
2529
+ label: "Minimum |\u0394PSI|",
2530
+ type: "number",
2531
+ chartType: "volcano",
2532
+ settingsKey: "deltaPsiCutoff",
2533
+ title: "Clusters must shift at least this much in PSI to count as significant. 0.05 = 5 percentage points.",
2534
+ min: 0,
2535
+ max: 1,
2536
+ step: 0.01
2537
+ }
2538
+ ];
2539
+ this.inputs.splice(0, 0, ...dsInputs);
2540
+ }
2541
+ // only edgeR is wired; add leafcutter here later
2542
+ getSpliceMethodOptions() {
2543
+ if (this.termType !== JUNCTION) return;
2544
+ return [{ label: "edgeR (diffSplice)", value: "edgeR" }];
2545
+ }
2546
+ getMethodOptions() {
2547
+ if (this.termType !== GENE_EXPRESSION) return;
2548
+ const features = JSON.parse(sessionStorage.getItem("optionalFeatures"));
2549
+ if (features?.runDE_methods?.length) {
2550
+ const opts = [];
2551
+ for (const m of features.runDE_methods) {
2552
+ opts.push({ label: m, value: m.toLowerCase() });
2553
+ }
2554
+ return opts;
2555
+ }
2556
+ return [
2557
+ { label: "edgeR", value: "edgeR" },
2558
+ { label: "Wilcoxon", value: "wilcoxon" },
2559
+ { label: "Limma", value: "limma" }
2560
+ ];
2561
+ }
2562
+ };
2563
+
2564
+ // plots/volcano/Volcano.ts
2565
+ var MIN_WILCOXON_GROUP_SIZE = 20;
2566
+ var Volcano = class _Volcano extends PlotBase {
2567
+ static {
2568
+ this.type = "volcano";
2569
+ }
2570
+ constructor(opts, api) {
2571
+ super(opts, api);
2572
+ if (this.opts.parentId) this.parentId = this.opts.parentId;
2573
+ this.type = _Volcano.type;
2574
+ this.components = {
2575
+ controls: {}
2576
+ };
2577
+ this.termType = opts.termType;
2578
+ const holder = opts.holder.classed("sjpp-volcano-main", true).attr("data-testid", `sjpp-volcano-main-${opts.termType}`);
2579
+ const controls = typeof opts.controls == "object" ? opts.controls : holder || holder.append("div");
2580
+ const error = opts.holder.append("div").attr("id", "sjpp-volcano-error").attr("data-testid", `sjpp-volcano-error-${opts.termType}`).style("opacity", 0.75);
2581
+ this.dom = {
2582
+ holder,
2583
+ controls,
2584
+ error,
2585
+ wait: holder.append("div").attr("id", "sjpp-volcano-wait").attr("data-testid", `sjpp-volcano-wait-${opts.termType}`).style("opacity", 0.75).style("padding", "20px").text("Loading..."),
2586
+ tip: new Menu({ padding: "" }),
2587
+ actionsTip: new Menu({ padding: "" })
2588
+ };
2589
+ }
2590
+ getState(appState) {
2591
+ const config = appState.plots.find((p) => p.id === this.id);
2592
+ if (!config) {
2593
+ throw new Error(
2594
+ `No plot with id='${this.id}' found. Did you set this.id before this.api = getComponentApi(this)?`
2595
+ );
2596
+ }
2597
+ const parentConfig = this.parentId && appState.plots.find((p) => p.id === this.parentId);
2598
+ const termfilter = getCombinedTermFilter(appState, config.filter || parentConfig?.filter);
2599
+ return {
2600
+ config: Object.assign({}, config, {
2601
+ settings: {
2602
+ volcano: config.settings.volcano
2603
+ }
2604
+ }),
2605
+ termfilter
2606
+ };
2607
+ }
2608
+ async setControls() {
2609
+ const plotConfig = this.app.getState().plots.find((p) => p.id === this.id);
2610
+ const controls = new VolcanoControlInputs(
2611
+ plotConfig,
2612
+ this.termType,
2613
+ this.app.vocabApi.termdbConfig?.queries?.dnaMethylation?.elementTypes,
2614
+ this.app.opts.genome?.majorchrorder
2615
+ );
2616
+ this.components.controls = await controlsInit({
2617
+ app: this.app,
2618
+ id: this.id,
2619
+ holder: this.dom.controls.style("display", "inline-block"),
2620
+ inputs: controls.inputs
2621
+ });
2622
+ this.components.controls.on("downloadClick.volcano", () => this.interactions.download(this.termType));
2623
+ if (plotConfig.chartType == "differentialAnalysis")
2624
+ this.components.controls.on(
2625
+ "helpClick.differentialAnalysis",
2626
+ () => (
2627
+ //Opens the page for the differential analysis wiki
2628
+ //Can't put in parent as DA does not have a controls component
2629
+ window.open("https://github.com/stjude/proteinpaint/wiki/Differential-analysis")
2630
+ )
2631
+ );
2632
+ }
2633
+ async init() {
2634
+ this.interactions = new VolcanoInteractions(this.app, this.id, this.dom);
2635
+ this.model = new VolcanoModel(this, this.termType);
2636
+ this.view = new VolcanoPlotView(this.dom, this.interactions, this.termType);
2637
+ await this.setControls();
2638
+ }
2639
+ async main() {
2640
+ if (!this.interactions) throw new Error("Volcano Interactions not initialized");
2641
+ if (!this.model) throw new Error("Volcano Model not initialized");
2642
+ if (!this.view) throw new Error("Volcano View not initialized");
2643
+ const config = structuredClone(this.state.config);
2644
+ if (config.chartType != this.type && config.childType != this.type) return;
2645
+ const settings = config.settings.volcano;
2646
+ let showWait, stopTimer;
2647
+ try {
2648
+ const isScan2 = settings.elementType == DMR_SCAN_ELEMENT_TYPE;
2649
+ const waitText = !isScan2 ? "Loading..." : `Scanning the genome for DMRs${settings.scanChromosome ? ` to show ${settings.scanChromosome}` : ""}... the first scan of a comparison can take a minute or more, and is cached after that.`;
2650
+ this.dom.wait.text(waitText);
2651
+ showWait = setTimeout(() => {
2652
+ this.dom.wait.style("display", "block");
2653
+ }, 500);
2654
+ if (this.termType == DNA_METHYLATION) stopTimer = startElapsedTimer(this.dom.wait, waitText);
2655
+ const response = await this.model.getData(config, settings);
2656
+ this.dom.error.text("");
2657
+ if (!response || response.error || !response.data || !response.data.volcanoPng || !response.data.totalRows) {
2658
+ const msg = response?.error || "No data returned from server";
2659
+ if (response?.code === "CACHE_BUSY") {
2660
+ if (window.confirm(msg)) this.main();
2661
+ } else sayerror(this.dom.error, msg);
2662
+ return;
2663
+ }
2664
+ const viewModel = new VolcanoViewModel(config, response, settings);
2665
+ this.interactions.pValueTableData = viewModel.viewData.pValueTableData;
2666
+ this.interactions.data = response.data.dots;
2667
+ this.interactions.daRequest = response.daRequest;
2668
+ this.interactions.totalSignificantRows = response.data.totalSignificantRows;
2669
+ this.interactions.provenance = viewModel.viewData.provenance;
2670
+ this.interactions.fetchAllRows = async () => {
2671
+ const full = await new VolcanoModel(this, this.termType).getData(config, {
2672
+ ...settings,
2673
+ maxInteractiveDots: null
2674
+ });
2675
+ if (!full || full.error || !full.data?.dots) throw new Error(full?.error || "no rows returned");
2676
+ return new VolcanoViewModel(config, full, settings).viewData.pValueTableData;
2677
+ };
2678
+ this.view.render(settings, viewModel.viewData);
2679
+ const notes = [];
2680
+ if (!response.data.dots.length) notes.push("No points passed the significance thresholds.");
2681
+ const smallestGroup = Math.min(response.sample_size1, response.sample_size2);
2682
+ if (settings.method == "wilcoxon" && smallestGroup < MIN_WILCOXON_GROUP_SIZE) {
2683
+ const samplesLabel = uiLabel(this.app.vocabApi.termdbConfig?.uiLabels, "samples", "samples");
2684
+ notes.push(
2685
+ `The smaller group has ${smallestGroup.toLocaleString()} ${samplesLabel}. Wilcoxon p-values are approximated here, and a gene that is zero in most ${samplesLabel} can be assigned a p-value far smaller than its group sizes can support. Rank these results by fold change rather than by p-value magnitude, and do not compare the p-values against another analysis.`
2686
+ );
2687
+ }
2688
+ if (notes.length) this.dom.error.text(notes.join(" ")).style("color", "#555");
2689
+ } catch (e) {
2690
+ if (e instanceof Error) console.error(e.message || e);
2691
+ else if (e.stack) console.log(e.stack);
2692
+ throw e;
2693
+ } finally {
2694
+ clearTimeout(showWait);
2695
+ stopTimer?.();
2696
+ this.dom.wait.style("display", "none");
2697
+ }
2698
+ }
2699
+ };
2700
+ var volcanoInit = getCompInit(Volcano);
2701
+ var componentInit = volcanoInit;
2702
+ async function getPlotConfig(opts, app) {
2703
+ if (!opts.termType) throw new Error(".termType is required");
2704
+ const config = {
2705
+ settings: {
2706
+ // app is passed through so the defaults can read the dataset's preferred starting
2707
+ // element class from termdbConfig; opts alone does not carry it
2708
+ volcano: getDefaultVolcanoSettings(opts.overrides, { ...opts, app })
2709
+ },
2710
+ highlightedData: opts.highlightedData || [],
2711
+ termType: opts.termType
2712
+ };
2713
+ if (opts.termType == GENE_EXPRESSION || opts.termType == DNA_METHYLATION) {
2714
+ if (opts.confounderTws) {
2715
+ try {
2716
+ for (const tw of opts.confounderTws) {
2717
+ await fillTermWrapper(tw, app.vocabApi);
2718
+ }
2719
+ } catch (e) {
2720
+ console.error(e.message || e);
2721
+ throw new Error(`Volcano getPlotConfig() failed to fill confounder term wrappers: ${e}`);
2722
+ }
2723
+ }
2724
+ Object.assign(config, {
2725
+ confounderTws: opts.confounderTws || [],
2726
+ samplelst: opts.samplelst
2727
+ });
2728
+ }
2729
+ if (opts.termType == SINGLECELL_CELLTYPE) {
2730
+ Object.assign(config, {
2731
+ //TODO: Fix this logic
2732
+ sample: opts.experimentID || opts.sample || opts.samples?.[0]?.experiments[0]?.experimentID,
2733
+ termId: app.vocabApi.termdbConfig.queries.singleCell.DEgenes.termId,
2734
+ //TODO: 'Cluster' is a fallback for development
2735
+ //Should require opts.categoryName in the future
2736
+ categoryName: opts.categoryName || "Cluster"
2737
+ });
2738
+ }
2739
+ validateVolcanoSettings(config, opts);
2740
+ return copyMerge(config, opts);
2741
+ }
2742
+ export {
2743
+ Volcano,
2744
+ componentInit,
2745
+ getPlotConfig,
2746
+ volcanoInit
2747
+ };
2748
+ //# sourceMappingURL=Volcano-62II76B4.js.map