diff --git a/browser/cypress/fixtures/grch37_reference_stub.json b/browser/cypress/fixtures/grch37_reference_stub.json
index 7d6cf9440..8a0c5738b 100644
--- a/browser/cypress/fixtures/grch37_reference_stub.json
+++ b/browser/cypress/fixtures/grch37_reference_stub.json
@@ -1342,6 +1342,7 @@
"flags": []
},
"exac_regional_missense_constraint_regions": null,
+ "gnomad_v2_regional_missense_constraint_regions": null,
"heterozygous_variant_cooccurrence_counts": [
{
"csq": "lof_lof",
diff --git a/browser/src/GenePage/GenePage.tsx b/browser/src/GenePage/GenePage.tsx
index 8a11e5aa4..a215a0573 100644
--- a/browser/src/GenePage/GenePage.tsx
+++ b/browser/src/GenePage/GenePage.tsx
@@ -19,6 +19,7 @@ import {
ReferenceGenome,
hasExons,
isExac,
+ isV2,
} from '@gnomad/dataset-metadata/metadata'
import ConstraintTable from '../ConstraintTable/ConstraintTable'
import VariantCooccurrenceCountsTable, {
@@ -31,6 +32,7 @@ import GnomadPageHeading from '../GnomadPageHeading'
import InfoButton from '../help/InfoButton'
import Link from '../Link'
import RegionalConstraintTrack from '../RegionalConstraintTrack'
+import RegionalMissenseConstraintTrack, { RegionalMissenseConstraint} from '../RegionalMissenseConstraintTrack'
import RegionCoverageTrack from '../RegionPage/RegionCoverageTrack'
import RegionViewer from '../RegionViewer/ZoomableRegionViewer'
import { TrackPage, TrackPageSection } from '../TrackPage'
@@ -106,6 +108,7 @@ export type Gene = GeneMetadata & {
id: string
}[]
exac_regional_missense_constraint_regions?: any
+ gnomad_v2_regional_missense_constraint?: RegionalMissenseConstraint
variants: Variant[]
structural_variants: StructuralVariant[]
clinvar_variants: ClinvarVariant[]
@@ -568,6 +571,13 @@ const GenePage = ({ datasetId, gene, geneId }: Props) => {
/>
)}
+ {isV2(datasetId) && (
+ <RegionalMissenseConstraintTrack
+ regionalMissenseConstraint={gene.gnomad_v2_regional_missense_constraint}
+ gene={gene}
+ />
+ )}
+
{/* eslint-disable-next-line no-nested-ternary */}
{hasStructuralVariants(datasetId) ? (
<StructuralVariantsInGene datasetId={datasetId} gene={gene} zoomRegion={zoomRegion} />
diff --git a/browser/src/GenePage/GenePageContainer.tsx b/browser/src/GenePage/GenePageContainer.tsx
index 694f1c4bc..e78711c20 100644
--- a/browser/src/GenePage/GenePageContainer.tsx
+++ b/browser/src/GenePage/GenePageContainer.tsx
@@ -224,6 +224,22 @@ query ${operationName}($geneId: String, $geneSymbol: String, $referenceGenome: R
obs_exp
chisq_diff_null
}
+ gnomad_v2_regional_missense_constraint {
+ passed_qc
+ has_no_rmc_evidence
+ regions {
+ chrom
+ start
+ stop
+ aa_start
+ aa_stop
+ obs_mis
+ exp_mis
+ obs_exp
+ chisq_diff_null
+ p_value
+ }
+ }
short_tandem_repeats(dataset: $shortTandemRepeatDatasetId) @include(if: $includeShortTandemRepeats) {
id
}
diff --git a/browser/src/GenePage/__snapshots__/GenePage.spec.tsx.snap b/browser/src/GenePage/__snapshots__/GenePage.spec.tsx.snap
index 7288a560d..adf955538 100644
--- a/browser/src/GenePage/__snapshots__/GenePage.spec.tsx.snap
+++ b/browser/src/GenePage/__snapshots__/GenePage.spec.tsx.snap
@@ -8584,6 +8584,101 @@ exports[`GenePage with non-SV dataset "gnomad_r2_1" has no unexpected changes 1`
</div>
</div>
</div>
+ <div
+ className="Track__OuterWrapper-sc-1sdyh2h-0 bBMGlf"
+ >
+ <div
+ className="Track__InnerWrapper-sc-1sdyh2h-1 cEOGGC"
+ >
+ <div
+ className="Track__SidePanel-sc-1sdyh2h-3 iSYzDq"
+ style={
+ {
+ "width": 115,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__SidePanel-sc-1lzrnv-4 clrqtu"
+ >
+ <span>
+ Regional missense constraint
+ </span>
+ <button
+ className="InfoButton__Button-sc-13t5e82-0 gxsoyZ"
+ onClick={[Function]}
+ type="button"
+ >
+ <img
+ alt=""
+ aria-hidden="true"
+ src="test-file-stub"
+ />
+ <span
+ style={
+ {
+ "border": "0",
+ "clip": "rect(0 0 0 0)",
+ "height": "1px",
+ "margin": "-1px",
+ "overflow": "hidden",
+ "padding": "0",
+ "position": "absolute",
+ "whiteSpace": "nowrap",
+ "width": "1px",
+ }
+ }
+ >
+ More information
+ </span>
+ </button>
+ </div>
+ </div>
+ <div
+ className="Track__CenterPanel-sc-1sdyh2h-4 iAyrrk"
+ style={
+ {
+ "width": 799,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__PlotWrapper-sc-1lzrnv-1 liGyhW"
+ >
+ <svg
+ height={35}
+ width={799}
+ >
+ <text
+ dy="1.0rem"
+ textAnchor="middle"
+ x={399.5}
+ y={17.5}
+ >
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our
+
+ </tspan>
+ <tspan
+ fill="#0000ff"
+ >
+ <a
+ className="Link-sc-14lgydv-0-Link jBvaYQ"
+ href="/help"
+ onClick={[Function]}
+ >
+ help page
+ </a>
+ </tspan>
+ <tspan>
+ for additional information.
+ </tspan>
+ </text>
+ </svg>
+ </div>
+ </div>
+ </div>
+ </div>
<div
className="TrackPage__TrackPageSection-sc-1xq3qi7-1 fQVUsz"
>
@@ -10043,6 +10138,101 @@ exports[`GenePage with non-SV dataset "gnomad_r2_1_controls" has no unexpected c
</div>
</div>
</div>
+ <div
+ className="Track__OuterWrapper-sc-1sdyh2h-0 bBMGlf"
+ >
+ <div
+ className="Track__InnerWrapper-sc-1sdyh2h-1 cEOGGC"
+ >
+ <div
+ className="Track__SidePanel-sc-1sdyh2h-3 iSYzDq"
+ style={
+ {
+ "width": 115,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__SidePanel-sc-1lzrnv-4 clrqtu"
+ >
+ <span>
+ Regional missense constraint
+ </span>
+ <button
+ className="InfoButton__Button-sc-13t5e82-0 gxsoyZ"
+ onClick={[Function]}
+ type="button"
+ >
+ <img
+ alt=""
+ aria-hidden="true"
+ src="test-file-stub"
+ />
+ <span
+ style={
+ {
+ "border": "0",
+ "clip": "rect(0 0 0 0)",
+ "height": "1px",
+ "margin": "-1px",
+ "overflow": "hidden",
+ "padding": "0",
+ "position": "absolute",
+ "whiteSpace": "nowrap",
+ "width": "1px",
+ }
+ }
+ >
+ More information
+ </span>
+ </button>
+ </div>
+ </div>
+ <div
+ className="Track__CenterPanel-sc-1sdyh2h-4 iAyrrk"
+ style={
+ {
+ "width": 799,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__PlotWrapper-sc-1lzrnv-1 liGyhW"
+ >
+ <svg
+ height={35}
+ width={799}
+ >
+ <text
+ dy="1.0rem"
+ textAnchor="middle"
+ x={399.5}
+ y={17.5}
+ >
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our
+
+ </tspan>
+ <tspan
+ fill="#0000ff"
+ >
+ <a
+ className="Link-sc-14lgydv-0-Link jBvaYQ"
+ href="/help"
+ onClick={[Function]}
+ >
+ help page
+ </a>
+ </tspan>
+ <tspan>
+ for additional information.
+ </tspan>
+ </text>
+ </svg>
+ </div>
+ </div>
+ </div>
+ </div>
<div
className="TrackPage__TrackPageSection-sc-1xq3qi7-1 fQVUsz"
>
@@ -11502,6 +11692,101 @@ exports[`GenePage with non-SV dataset "gnomad_r2_1_non_cancer" has no unexpected
</div>
</div>
</div>
+ <div
+ className="Track__OuterWrapper-sc-1sdyh2h-0 bBMGlf"
+ >
+ <div
+ className="Track__InnerWrapper-sc-1sdyh2h-1 cEOGGC"
+ >
+ <div
+ className="Track__SidePanel-sc-1sdyh2h-3 iSYzDq"
+ style={
+ {
+ "width": 115,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__SidePanel-sc-1lzrnv-4 clrqtu"
+ >
+ <span>
+ Regional missense constraint
+ </span>
+ <button
+ className="InfoButton__Button-sc-13t5e82-0 gxsoyZ"
+ onClick={[Function]}
+ type="button"
+ >
+ <img
+ alt=""
+ aria-hidden="true"
+ src="test-file-stub"
+ />
+ <span
+ style={
+ {
+ "border": "0",
+ "clip": "rect(0 0 0 0)",
+ "height": "1px",
+ "margin": "-1px",
+ "overflow": "hidden",
+ "padding": "0",
+ "position": "absolute",
+ "whiteSpace": "nowrap",
+ "width": "1px",
+ }
+ }
+ >
+ More information
+ </span>
+ </button>
+ </div>
+ </div>
+ <div
+ className="Track__CenterPanel-sc-1sdyh2h-4 iAyrrk"
+ style={
+ {
+ "width": 799,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__PlotWrapper-sc-1lzrnv-1 liGyhW"
+ >
+ <svg
+ height={35}
+ width={799}
+ >
+ <text
+ dy="1.0rem"
+ textAnchor="middle"
+ x={399.5}
+ y={17.5}
+ >
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our
+
+ </tspan>
+ <tspan
+ fill="#0000ff"
+ >
+ <a
+ className="Link-sc-14lgydv-0-Link jBvaYQ"
+ href="/help"
+ onClick={[Function]}
+ >
+ help page
+ </a>
+ </tspan>
+ <tspan>
+ for additional information.
+ </tspan>
+ </text>
+ </svg>
+ </div>
+ </div>
+ </div>
+ </div>
<div
className="TrackPage__TrackPageSection-sc-1xq3qi7-1 fQVUsz"
>
@@ -12961,6 +13246,101 @@ exports[`GenePage with non-SV dataset "gnomad_r2_1_non_neuro" has no unexpected
</div>
</div>
</div>
+ <div
+ className="Track__OuterWrapper-sc-1sdyh2h-0 bBMGlf"
+ >
+ <div
+ className="Track__InnerWrapper-sc-1sdyh2h-1 cEOGGC"
+ >
+ <div
+ className="Track__SidePanel-sc-1sdyh2h-3 iSYzDq"
+ style={
+ {
+ "width": 115,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__SidePanel-sc-1lzrnv-4 clrqtu"
+ >
+ <span>
+ Regional missense constraint
+ </span>
+ <button
+ className="InfoButton__Button-sc-13t5e82-0 gxsoyZ"
+ onClick={[Function]}
+ type="button"
+ >
+ <img
+ alt=""
+ aria-hidden="true"
+ src="test-file-stub"
+ />
+ <span
+ style={
+ {
+ "border": "0",
+ "clip": "rect(0 0 0 0)",
+ "height": "1px",
+ "margin": "-1px",
+ "overflow": "hidden",
+ "padding": "0",
+ "position": "absolute",
+ "whiteSpace": "nowrap",
+ "width": "1px",
+ }
+ }
+ >
+ More information
+ </span>
+ </button>
+ </div>
+ </div>
+ <div
+ className="Track__CenterPanel-sc-1sdyh2h-4 iAyrrk"
+ style={
+ {
+ "width": 799,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__PlotWrapper-sc-1lzrnv-1 liGyhW"
+ >
+ <svg
+ height={35}
+ width={799}
+ >
+ <text
+ dy="1.0rem"
+ textAnchor="middle"
+ x={399.5}
+ y={17.5}
+ >
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our
+
+ </tspan>
+ <tspan
+ fill="#0000ff"
+ >
+ <a
+ className="Link-sc-14lgydv-0-Link jBvaYQ"
+ href="/help"
+ onClick={[Function]}
+ >
+ help page
+ </a>
+ </tspan>
+ <tspan>
+ for additional information.
+ </tspan>
+ </text>
+ </svg>
+ </div>
+ </div>
+ </div>
+ </div>
<div
className="TrackPage__TrackPageSection-sc-1xq3qi7-1 fQVUsz"
>
@@ -14420,6 +14800,101 @@ exports[`GenePage with non-SV dataset "gnomad_r2_1_non_topmed" has no unexpected
</div>
</div>
</div>
+ <div
+ className="Track__OuterWrapper-sc-1sdyh2h-0 bBMGlf"
+ >
+ <div
+ className="Track__InnerWrapper-sc-1sdyh2h-1 cEOGGC"
+ >
+ <div
+ className="Track__SidePanel-sc-1sdyh2h-3 iSYzDq"
+ style={
+ {
+ "width": 115,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__SidePanel-sc-1lzrnv-4 clrqtu"
+ >
+ <span>
+ Regional missense constraint
+ </span>
+ <button
+ className="InfoButton__Button-sc-13t5e82-0 gxsoyZ"
+ onClick={[Function]}
+ type="button"
+ >
+ <img
+ alt=""
+ aria-hidden="true"
+ src="test-file-stub"
+ />
+ <span
+ style={
+ {
+ "border": "0",
+ "clip": "rect(0 0 0 0)",
+ "height": "1px",
+ "margin": "-1px",
+ "overflow": "hidden",
+ "padding": "0",
+ "position": "absolute",
+ "whiteSpace": "nowrap",
+ "width": "1px",
+ }
+ }
+ >
+ More information
+ </span>
+ </button>
+ </div>
+ </div>
+ <div
+ className="Track__CenterPanel-sc-1sdyh2h-4 iAyrrk"
+ style={
+ {
+ "width": 799,
+ }
+ }
+ >
+ <div
+ className="RegionalMissenseConstraintTrack__PlotWrapper-sc-1lzrnv-1 liGyhW"
+ >
+ <svg
+ height={35}
+ width={799}
+ >
+ <text
+ dy="1.0rem"
+ textAnchor="middle"
+ x={399.5}
+ y={17.5}
+ >
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our
+
+ </tspan>
+ <tspan
+ fill="#0000ff"
+ >
+ <a
+ className="Link-sc-14lgydv-0-Link jBvaYQ"
+ href="/help"
+ onClick={[Function]}
+ >
+ help page
+ </a>
+ </tspan>
+ <tspan>
+ for additional information.
+ </tspan>
+ </text>
+ </svg>
+ </div>
+ </div>
+ </div>
+ </div>
<div
className="TrackPage__TrackPageSection-sc-1xq3qi7-1 fQVUsz"
>
diff --git a/browser/src/RegionalMissenseConstraintTrack.spec.tsx b/browser/src/RegionalMissenseConstraintTrack.spec.tsx
new file mode 100644
index 000000000..4d6969090
--- /dev/null
+++ b/browser/src/RegionalMissenseConstraintTrack.spec.tsx
@@ -0,0 +1,56 @@
+import { describe, expect, test } from '@jest/globals'
+
+// eslint-disable-next-line import/no-unresolved, import/extensions
+import { regionIntersections } from './RegionalMissenseConstraintTrack'
+
+describe('RegionaMissenseConstraintTrack', () => {
+ test('regionIntersections', () => {
+ const testCases = [
+ {
+ regions1: [
+ { start: 2, stop: 4, i: 1 },
+ { start: 6, stop: 8, i: 2 },
+ ],
+ regions2: [
+ { start: 2, stop: 6, j: 1 },
+ { start: 6, stop: 9, j: 2 },
+ ],
+ expected: [
+ { start: 2, stop: 4, i: 1, j: 1 },
+ { start: 6, stop: 8, i: 2, j: 2 },
+ ],
+ },
+ {
+ regions1: [
+ { start: 2, stop: 4, i: 1 },
+ { start: 6, stop: 8, i: 2 },
+ ],
+ regions2: [{ start: 1, stop: 8, j: 1 }],
+ expected: [
+ { start: 2, stop: 4, i: 1, j: 1 },
+ { start: 6, stop: 8, i: 2, j: 1 },
+ ],
+ },
+ {
+ regions1: [
+ { start: 2, stop: 4, i: 1 },
+ { start: 6, stop: 8, i: 2 },
+ ],
+ regions2: [
+ { start: 1, stop: 3, j: 1 },
+ { start: 3, stop: 5, j: 2 },
+ { start: 5, stop: 9, j: 3 },
+ ],
+ expected: [
+ { start: 2, stop: 3, i: 1, j: 1 },
+ { start: 3, stop: 4, i: 1, j: 2 },
+ { start: 6, stop: 8, i: 2, j: 3 },
+ ],
+ },
+ ]
+
+ testCases.forEach(({ regions1, regions2, expected }) => {
+ expect(regionIntersections([regions1, regions2])).toEqual(expected)
+ })
+ })
+})
diff --git a/browser/src/RegionalMissenseConstraintTrack.tsx b/browser/src/RegionalMissenseConstraintTrack.tsx
new file mode 100644
index 000000000..7757d4e4d
--- /dev/null
+++ b/browser/src/RegionalMissenseConstraintTrack.tsx
@@ -0,0 +1,444 @@
+import React from 'react'
+import styled from 'styled-components'
+
+// @ts-expect-error TS(7016) FIXME: Could not find a declaration file for module '@gno... Remove this comment to see the full error message
+import { Track } from '@gnomad/region-viewer'
+import { TooltipAnchor } from '@gnomad/ui'
+
+import Link from './Link'
+
+import InfoButton from './help/InfoButton'
+import { Gene } from './GenePage/GenePage'
+
+type RegionalMissenseConstraintRegion = {
+ chrom: string
+ start: number
+ stop: number
+ aa_start: string | null
+ aa_stop: string | null
+ obs_mis: number | undefined
+ exp_mis: number
+ obs_exp: number
+ chisq_diff_null: number | undefined
+ p_value: number
+ z_score: number | undefined
+}
+
+const Wrapper = styled.div`
+ display: flex;
+ flex-direction: column;
+ margin-bottom: 1em;
+`
+
+const PlotWrapper = styled.div`
+ display: flex;
+ flex-direction: column;
+ justify-content: center;
+ height: 100%;
+`
+
+const RegionAttributeList = styled.dl`
+ margin: 0;
+
+ div {
+ margin-bottom: 0.25em;
+ }
+
+ dt {
+ display: inline;
+ font-weight: bold;
+ }
+
+ dd {
+ display: inline;
+ margin-left: 0.5em;
+ }
+`
+
+export const regionIntersections = (regionArrays: { start: number; stop: number }[][]) => {
+ const sortedRegionsArrays = regionArrays.map((regions) =>
+ [...regions].sort((a, b) => a.start - b.start)
+ )
+
+ const intersections = []
+
+ const indices = sortedRegionsArrays.map(() => 0)
+
+ while (sortedRegionsArrays.every((regions, i) => indices[i] < regions.length)) {
+ const maxStart = Math.max(...sortedRegionsArrays.map((regions, i) => regions[indices[i]].start))
+ const minStop = Math.min(...sortedRegionsArrays.map((regions, i) => regions[indices[i]].stop))
+
+ if (maxStart < minStop) {
+ const next = Object.assign(
+ // @ts-ignore TS2556: A spread argument must either have a tuple type or be ...
+ ...[
+ {},
+ ...sortedRegionsArrays.map((regions: { [x: string]: any }, i) => regions[indices[i]]),
+ {
+ start: maxStart,
+ stop: minStop,
+ },
+ ]
+ )
+
+ intersections.push(next)
+ }
+
+ sortedRegionsArrays.forEach((regions, i) => {
+ if (regions[indices[i]].stop === minStop) {
+ indices[i] += 1
+ }
+ })
+ }
+
+ return intersections
+}
+
+// https://colorbrewer2.org/#type=sequential&scheme=YlOrRd&n=5
+const colorScale = {
+ not_significant: '#e2e2e2',
+ least: '#9b001f',
+ less: '#de351b',
+ middle: '#fd8d3c',
+ greater: '#fecc5c',
+ greatest: '#ffffb2',
+}
+
+function regionColor(region: RegionalMissenseConstraintRegion) {
+ if (region.z_score) {
+ return region.z_score > 3.09 ? colorScale.middle : colorScale.not_significant
+ }
+
+ let color
+ if (region.obs_exp > 0.8) {
+ color = colorScale.greatest
+ } else if (region.obs_exp > 0.6) {
+ color = colorScale.greater
+ } else if (region.obs_exp > 0.4) {
+ color = colorScale.middle
+ } else if (region.obs_exp > 0.2) {
+ color = colorScale.less
+ } else {
+ color = colorScale.least
+ }
+
+ return region.p_value > 0.001 ? colorScale.not_significant : color
+}
+
+const LegendWrapper = styled.div`
+ display: flex;
+
+ @media (max-width: 600px) {
+ flex-direction: column;
+ align-items: center;
+ }
+`
+
+const Legend = () => {
+ return (
+ <LegendWrapper>
+ <span>Missense observed/expected</span>
+ <svg width={170} height={25}>
+ <rect x={10} y={0} width={30} height={10} stroke="#000" fill={colorScale.least} />
+ <rect x={40} y={0} width={30} height={10} stroke="#000" fill={colorScale.less} />
+ <rect x={70} y={0} width={30} height={10} stroke="#000" fill={colorScale.middle} />
+ <rect x={100} y={0} width={30} height={10} stroke="#000" fill={colorScale.greater} />
+ <rect x={130} y={0} width={30} height={10} stroke="#000" fill={colorScale.greatest} />
+ <text x={10} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 0.0
+ </text>
+ <text x={40} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 0.2
+ </text>
+ <text x={70} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 0.4
+ </text>
+ <text x={100} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 0.6
+ </text>
+ <text x={130} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 0.8
+ </text>
+ <text x={160} y={10} fontSize="10" dy="1.2em" textAnchor="middle">
+ 1.0+
+ </text>
+ </svg>
+ <svg width={170} height={25}>
+ <rect x={10} y={0} width={20} height={10} stroke="#000" fill={colorScale.not_significant} />
+ <text x={35} y={0} fontSize="10" dy="1em" textAnchor="start">
+ Not significant (p > 1e-3)
+ </text>
+ </svg>
+ </LegendWrapper>
+ )
+}
+
+const renderNumber = (number: number | undefined) => {
+ return number === undefined || number === null ? '-' : number.toPrecision(4)
+}
+
+const renderNumberExponential = (number: number | undefined) => {
+ return number === undefined || number === null ? '-' : number.toExponential(3)
+}
+
+const printAAorNA = (aa: string | null) => {
+ if (aa === null) {
+ return 'n/a'
+ }
+ return aa
+}
+
+type RegionTooltipProps = {
+ region: RegionalMissenseConstraintRegion
+ isTranscriptWide: boolean
+}
+
+const RegionTooltip = ({ region, isTranscriptWide }: RegionTooltipProps) => {
+ if (isTranscriptWide) {
+ return (
+ <RegionAttributeList>
+ <div>
+ <dt>Missense observed/expected:</dt>
+ <dd>{`${renderNumber(region.obs_exp)} (${region.obs_mis}/${renderNumber(
+ region.exp_mis
+ )})`}</dd>
+ </div>
+ <br />
+ <div>The observed/expected ratio for this gene is transcript-wide.</div>
+ </RegionAttributeList>
+ )
+ }
+ return (
+ <RegionAttributeList>
+ <div>
+ <dt>Coordinates:</dt>
+ <dd>{`${region.chrom}:${region.start}-${region.stop}`}</dd>
+ </div>
+ <div>
+ <dt>Amino acids:</dt>
+ <dd>{`${printAAorNA(region.aa_start)}-${printAAorNA(region.aa_stop)}`}</dd>
+ </div>
+ <div>
+ <dt>Missense observed/expected:</dt>
+ <dd>{`${renderNumber(region.obs_exp)} (${region.obs_mis}/${renderNumber(
+ region.exp_mis
+ )})`}</dd>
+ </div>
+ <div>
+ <dt>p-value:</dt>
+ <dd>
+ {renderNumberExponential(region.p_value)}
+ {region.p_value !== null && region.p_value > 0.001 && ' (not significant)'}
+ </dd>
+ </div>
+ </RegionAttributeList>
+ )
+}
+
+const SidePanel = styled.div`
+ display: flex;
+ align-items: center;
+ height: 100%;
+`
+
+const TopPanel = styled.div`
+ display: flex;
+ justify-content: flex-end;
+ width: 100%;
+ margin-bottom: 5px;
+`
+
+export type RegionalMissenseConstraint = {
+ has_no_rmc_evidence: boolean
+ passed_qc: boolean
+ regions: RegionalMissenseConstraintRegion[]
+}
+
+type Props = {
+ regionalMissenseConstraint?: RegionalMissenseConstraint
+ gene: Gene
+}
+
+type TrackProps = {
+ scalePosition: (input: number) => number
+ width: number
+}
+
+const RegionalMissenseConstraintTrack = ({ regionalMissenseConstraint, gene }: Props) => {
+ if (
+ !regionalMissenseConstraint ||
+ regionalMissenseConstraint.regions === null ||
+ (regionalMissenseConstraint.passed_qc === false &&
+ regionalMissenseConstraint.has_no_rmc_evidence === false)
+ ) {
+ return (
+ <Track
+ renderLeftPanel={() => (
+ <SidePanel>
+ <span>Regional missense constraint</span>
+ <InfoButton topic="regional-constraint" />
+ </SidePanel>
+ )}
+ >
+ {({ width }: { width: number }) => (
+ <>
+ <PlotWrapper>
+ <svg height={35} width={width}>
+ <text x={width / 2} y={35 / 2} dy="1.0rem" textAnchor="middle">
+ <tspan>
+ This gene was not searched for evidence of regional missense constraint. See our{' '}
+ </tspan>
+ <tspan fill="#0000ff">
+ <Link to="/help">help page</Link>
+ </tspan>
+ <tspan> for additional information.</tspan>
+ </text>
+ </svg>
+ </PlotWrapper>
+ </>
+ )}
+ </Track>
+ )
+ }
+
+ // This transcript was searched, but no RMC evidence was found
+ // instead, use the available gene level constraint data to display a single
+ // region for the RMC track
+ if (regionalMissenseConstraint.has_no_rmc_evidence) {
+ // eslint-disable-next-line no-param-reassign
+ regionalMissenseConstraint.regions = []
+
+ if (gene.gnomad_constraint) {
+ // eslint-disable-next-line no-param-reassign
+ regionalMissenseConstraint.regions = [
+ {
+ chrom: gene.chrom,
+ start: Math.min(gene.start, gene.stop),
+ stop: Math.max(gene.start, gene.stop),
+ obs_mis: gene.gnomad_constraint.obs_mis,
+ exp_mis: gene.gnomad_constraint.exp_mis,
+ obs_exp: gene.gnomad_constraint.oe_mis,
+ z_score: gene.gnomad_constraint.mis_z,
+ p_value: -0.01,
+ chisq_diff_null: undefined,
+ aa_start: null,
+ aa_stop: null,
+ },
+ ]
+ }
+ }
+
+ const constrainedExons = regionIntersections([
+ regionalMissenseConstraint.regions,
+ gene.exons.filter((exon) => exon.feature_type === 'CDS'),
+ ])
+
+ return (
+ <Wrapper>
+ <Track
+ renderLeftPanel={() => (
+ <SidePanel>
+ <span>Regional missense constraint</span>
+ <InfoButton topic="regional-constraint" />
+ </SidePanel>
+ )}
+ >
+ {({ scalePosition, width }: TrackProps) => (
+ <>
+ <TopPanel>
+ <Legend />
+ </TopPanel>
+ <PlotWrapper>
+ <svg height={55} width={width}>
+ {constrainedExons.map((region: RegionalMissenseConstraintRegion) => {
+ const startX = scalePosition(region.start)
+ const stopX = scalePosition(region.stop)
+ const regionWidth = stopX - startX
+
+ return (
+ <TooltipAnchor
+ key={`${region.start}-${region.stop}`}
+ // @ts-expect-error - from TooltipAnchor component of GBTK
+ region={region}
+ isTranscript={regionalMissenseConstraint.regions.length === 1}
+ tooltipComponent={RegionTooltip}
+ >
+ <g>
+ <rect
+ x={startX}
+ y={0}
+ width={regionWidth}
+ height={15}
+ fill={regionColor(region)}
+ stroke="black"
+ />
+ </g>
+ </TooltipAnchor>
+ )
+ })}
+ <g transform="translate(0,20)">
+ {regionalMissenseConstraint.regions.map(
+ (region: RegionalMissenseConstraintRegion, index: number) => {
+ const startX = scalePosition(region.start)
+ const stopX = scalePosition(region.stop)
+ const regionWidth = stopX - startX
+ const midX = (startX + stopX) / 2
+ // const offset = index * 15
+ const offset = index * 0
+
+ return (
+ <g key={`${region.start}-${region.stop}`}>
+ <line
+ x1={startX}
+ y1={2 + offset}
+ x2={startX}
+ y2={11 + offset}
+ stroke="#424242"
+ />
+ <line
+ x1={startX}
+ y1={7 + offset}
+ x2={stopX}
+ y2={7 + offset}
+ stroke="#424242"
+ />
+ <line
+ x1={stopX}
+ y1={2 + offset}
+ x2={stopX}
+ y2={11 + offset}
+ stroke="#424242"
+ />
+ {regionWidth > 40 && (
+ <>
+ <rect
+ x={midX - 15}
+ y={3 + offset}
+ width={30}
+ height={5}
+ fill="#fafafa"
+ />
+ <text x={midX} y={8 + offset} dy="0.33em" textAnchor="middle">
+ {region.obs_exp.toFixed(2)}
+ </text>
+ </>
+ )}
+ </g>
+ )
+ }
+ )}
+ </g>
+ </svg>
+ </PlotWrapper>
+ </>
+ )}
+ </Track>
+ </Wrapper>
+ )
+}
+
+RegionalMissenseConstraintTrack.defaultProps = {
+ height: 15,
+}
+
+export default RegionalMissenseConstraintTrack
diff --git a/data-pipeline/src/data_pipeline/datasets/gnomad_v2/gnomad_v2_regional_missense_constraint.py b/data-pipeline/src/data_pipeline/datasets/gnomad_v2/gnomad_v2_regional_missense_constraint.py
new file mode 100644
index 000000000..2dab02952
--- /dev/null
+++ b/data-pipeline/src/data_pipeline/datasets/gnomad_v2/gnomad_v2_regional_missense_constraint.py
@@ -0,0 +1,82 @@
+import hail as hl
+
+
+def prepare_gnomad_v2_regional_missense_constraint(path):
+ ds = hl.read_table(path)
+
+ # rename key field transcript_id to transcript to allow merging in genes pipeline
+ ds_with_rmc = ds.transmute(transcript_id=ds.transcript)
+ ds_with_rmc = ds_with_rmc.key_by("transcript_id")
+ ds_with_rmc = ds_with_rmc.drop("transcript")
+
+ # explode then collect to rename fields for consistency with ExAC RMC
+ ds_with_rmc = ds_with_rmc.explode("regions")
+ ds_with_rmc = ds_with_rmc.select(
+ regions=hl.struct(
+ chrom=ds_with_rmc.regions.start_coordinate.contig,
+ start=hl.min(ds_with_rmc.regions.start_coordinate.position, ds_with_rmc.regions.stop_coordinate.position),
+ stop=hl.max(ds_with_rmc.regions.start_coordinate.position, ds_with_rmc.regions.stop_coordinate.position),
+ aa_start=ds_with_rmc.regions.start_aa,
+ aa_stop=ds_with_rmc.regions.stop_aa,
+ obs_mis=ds_with_rmc.regions.obs,
+ exp_mis=ds_with_rmc.regions.exp,
+ obs_exp=ds_with_rmc.regions.oe,
+ chisq_diff_null=ds_with_rmc.regions.chisq,
+ p_value=ds_with_rmc.regions.p,
+ ),
+ )
+ ds_with_rmc = ds_with_rmc.group_by("transcript_id").aggregate(regions=hl.agg.collect(ds_with_rmc.row_value).regions)
+
+ ds_with_rmc = ds_with_rmc.group_by("transcript_id").aggregate(regions_array=hl.agg.collect(ds_with_rmc.row_value))
+ ds_with_rmc = ds_with_rmc.annotate(has_no_rmc_evidence=hl.bool(False))
+ ds_with_rmc = ds_with_rmc.annotate(
+ passed_qc=hl.if_else(
+ hl.set(ds_with_rmc.globals.rmc_transcripts_qc).contains(ds_with_rmc.transcript_id),
+ hl.bool(True),
+ hl.bool(False),
+ )
+ )
+ ds_with_rmc = ds_with_rmc.select(
+ has_no_rmc_evidence=ds_with_rmc.has_no_rmc_evidence,
+ passed_qc=ds_with_rmc.passed_qc,
+ regions=hl.sorted(ds_with_rmc.regions_array[0].regions, lambda region: region.start),
+ )
+
+ # create a hailtable with a row for every transcript included in the no_rmc set
+ # the browser needs to be able to distinguish between transcripts that were
+ # searched and had no RMC evidence, vs those that were not searched, for display
+ # purposes
+ no_rmc_set = ds.globals.transcripts_no_rmc_all
+ no_rmc_list = list(no_rmc_set.collect()[0])
+ ds_no_rmc = hl.utils.range_table(1)
+ ds_no_rmc = ds_no_rmc.annotate(
+ transcript_id=(hl.array(no_rmc_list)),
+ has_no_rmc_evidence=hl.bool(True),
+ passed_qc=hl.bool(False),
+ regions=hl.empty_array(
+ hl.tstruct(
+ chrom=hl.tstr,
+ start=hl.tint32,
+ stop=hl.tint32,
+ aa_start=hl.tstr,
+ aa_stop=hl.tstr,
+ obs_mis=hl.tint64,
+ exp_mis=hl.tfloat64,
+ obs_exp=hl.tfloat64,
+ chisq_diff_null=hl.tfloat64,
+ p_value=hl.tfloat64,
+ )
+ ),
+ )
+ ds_no_rmc = ds_no_rmc.explode(ds_no_rmc["transcript_id"])
+ ds_no_rmc = ds_no_rmc.key_by("transcript_id")
+ ds_no_rmc = ds_no_rmc.drop("idx")
+
+ # combine the hail table of those transcripts with evidence, and those transcripts
+ # searched without evidence
+ ds_all_searched = ds_with_rmc.union(ds_no_rmc)
+
+ # Don't need the information in globals for the browser
+ ds_all_searched = ds_all_searched.select_globals()
+
+ return ds_all_searched
diff --git a/data-pipeline/src/data_pipeline/pipelines/genes.py b/data-pipeline/src/data_pipeline/pipelines/genes.py
index 2ceddad60..c21c4e0c8 100644
--- a/data-pipeline/src/data_pipeline/pipelines/genes.py
+++ b/data-pipeline/src/data_pipeline/pipelines/genes.py
@@ -18,6 +18,9 @@
from data_pipeline.datasets.exac.exac_constraint import prepare_exac_constraint
from data_pipeline.datasets.exac.exac_regional_missense_constraint import prepare_exac_regional_missense_constraint
from data_pipeline.datasets.gnomad_v2.gnomad_v2_constraint import prepare_gnomad_v2_constraint
+from data_pipeline.datasets.gnomad_v2.gnomad_v2_regional_missense_constraint import (
+ prepare_gnomad_v2_regional_missense_constraint,
+)
from data_pipeline.pipelines.variant_cooccurrence_counts import (
annotate_table_with_variant_cooccurrence_counts,
@@ -199,6 +202,14 @@
"/genes/homozygous_variant_cooccurrence_counts.ht",
)
+pipeline.add_task(
+ "prepare_gnomad_v2_regional_missense_constraint",
+ prepare_gnomad_v2_regional_missense_constraint,
+ "/constraint/gnomad_v2_regional_missense_constraint.ht",
+ # TODO: before merging - update to a more permanent location for this data
+ {"path": "gs://gnomad-rgrant-data-pipeline/output/constraint/20230926_rmc_demo"},
+)
+
###############################################
# Annotate genes
###############################################
@@ -256,6 +267,7 @@ def annotate_with_preferred_transcript(table_path):
"exac_constraint": pipeline.get_task("prepare_exac_constraint"),
"exac_regional_missense_constraint": pipeline.get_task("prepare_exac_regional_missense_constraint"),
"gnomad_constraint": pipeline.get_task("prepare_gnomad_v2_constraint"),
+ "gnomad_v2_regional_missense_constraint": pipeline.get_task("prepare_gnomad_v2_regional_missense_constraint"),
},
{"join_on": "preferred_transcript_id"},
)
diff --git a/graphql-api/src/graphql/types/constraint/gnomad-regional-missense-constraint.graphql b/graphql-api/src/graphql/types/constraint/gnomad-regional-missense-constraint.graphql
new file mode 100644
index 000000000..310f3080f
--- /dev/null
+++ b/graphql-api/src/graphql/types/constraint/gnomad-regional-missense-constraint.graphql
@@ -0,0 +1,18 @@
+type GnomadV2RegionalMissenseConstraintRegion {
+ chrom: String
+ start: Int
+ stop: Int
+ aa_start: String
+ aa_stop: String
+ obs_mis: Int
+ exp_mis: Float
+ obs_exp: Float
+ chisq_diff_null: Float
+ p_value: Float
+}
+
+type GnomadV2RegionalMissenseConstraint {
+ has_no_rmc_evidence: Boolean
+ passed_qc: Boolean
+ regions: [GnomadV2RegionalMissenseConstraintRegion]
+}
diff --git a/graphql-api/src/graphql/types/gene.graphql b/graphql-api/src/graphql/types/gene.graphql
index 3dd245618..6fe57f3ff 100644
--- a/graphql-api/src/graphql/types/gene.graphql
+++ b/graphql-api/src/graphql/types/gene.graphql
@@ -65,6 +65,8 @@ type Gene {
pext: Pext
gnomad_constraint: GnomadConstraint
+ gnomad_v2_regional_missense_constraint: GnomadV2RegionalMissenseConstraint
+
exac_constraint: ExacConstraint
exac_regional_missense_constraint_regions: [ExacRegionalMissenseConstraintRegion!]