VA/VRS quality measures

graphql-api/src/graphql/resolvers/va.spec.ts

@@ -59,6 +59,13 @@ describe('resolveVACohortAlleleFrequency', () => {
     homozygote_count: 3,
     faf95: { popmax: 0.123, popmax_population: 'afr' },
     ancestry_groups: [],
+    filters: ['AC0'],
+    flags: ['monoallelic'],
+    quality_metrics: {
+      allele_balance: {
+        alt: { bin_freq: [0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19] },
+      },
+    },
   }
 
   const genomeEsDocument = {
@@ -67,7 +74,19 @@ describe('resolveVACohortAlleleFrequency', () => {
     hemizygote_count: 4,
     homozygote_count: 5,
     faf95: { popmax: 0.234, popmax_population: 'eas' },
+    filters: ['AC0'],
     ancestry_groups: [],
+    flags: ['monoallelic'],
+    quality_metrics: {
+      allele_balance: {
+        alt: {
+          bin_freq: [
+            100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116,
+            117, 118, 119,
+          ],
+        },
+      },
+    },
   }
 
   const variantESDocument = {
@@ -76,6 +95,8 @@ describe('resolveVACohortAlleleFrequency', () => {
     exome: exomeEsDocument,
     genome: genomeEsDocument,
     joint: { fafmax: { faf95_max: 0.234, faf95_max_gen_anc: 'amr' } },
+    coverage: { exome: { mean: 0.345, over_20: 0.456 }, genome: { mean: 0.111, over_20: 0.222 } },
+    flags: ['lcr', 'lc_lof', 'lof_flag'],
   }
 
   test('parses a single CohortAlleleFrequency exome correctly', async () => {
@@ -103,6 +124,16 @@ describe('resolveVACohortAlleleFrequency', () => {
           hemizygotes: 2,
         },
         subcohortFrequency: [],
+        qualityMeasures: {
+          meanDepth: 0.345,
+          fractionCoverage20x: 0.456,
+          qcFilters: ['AC0'],
+          monoallelic: true,
+          lowComplexityRegion: true,
+          lowConfidenceLossOfFunctionError: true,
+          lossOfFunctionWarning: true,
+          heterozygousSkewedAlleleCount: 37,
+        },
       },
     ]
 
@@ -134,6 +165,16 @@ describe('resolveVACohortAlleleFrequency', () => {
           hemizygotes: 4,
         },
         subcohortFrequency: [],
+        qualityMeasures: {
+          meanDepth: 0.111,
+          fractionCoverage20x: 0.222,
+          monoallelic: true,
+          qcFilters: ['AC0'],
+          lowComplexityRegion: true,
+          lowConfidenceLossOfFunctionError: true,
+          lossOfFunctionWarning: true,
+          heterozygousSkewedAlleleCount: 237,
+        },
       },
     ]
 

graphql-api/src/graphql/resolvers/va.ts

@@ -93,6 +93,17 @@ type AncillaryResults = {
   hemizygotes: number | null
 }
 
+type QualityMeasures = {
+  meanDepth: number | null
+  fractionCoverage20x: number | null
+  qcFilters: string[] | null
+  monoallelic: boolean | null
+  lowComplexityRegion: boolean | null
+  lowConfidenceLossOfFunctionError: boolean | null
+  lossOfFunctionWarning: boolean | null
+  heterozygousSkewedAlleleCount: number | null
+}
+
 export type CohortAlleleFrequency = {
   id: string
   type: string
@@ -104,6 +115,7 @@ export type CohortAlleleFrequency = {
   alleleFrequency: number
   cohort: Cohort
   ancillaryResults: AncillaryResults | null
+  qualityMeasures: QualityMeasures | null
   subcohortFrequency: CohortAlleleFrequency[]
 }
 
@@ -187,6 +199,7 @@ type Subset = {
   homozygote_count: number
   grpMax?: GrpMaxFAF95
   jointGrpMax?: GrpMaxFAF95
+  qualityMeasures: QualityMeasures
 }
 
 const GNOMAD_V4_DERIVATION = {
@@ -279,6 +292,7 @@ const resolveVACohortAlleleFrequency = (
     alleleFrequency: subset.ac / subset.an,
     cohort,
     ancillaryResults,
+    qualityMeasures: subset.qualityMeasures,
   }
 }
 
@@ -367,6 +381,25 @@ const addSubcohorts = (
   return Object.values(subcohortMap)
 }
 
+type ESFrequencies = {
+  quality_metrics: {
+    allele_balance: {
+      alt?: {
+        bin_freq: number[]
+      }
+    }
+  }
+}
+
+const calculateHeterozygousSkewedAlleleCount = (frequencies: ESFrequencies): number | null => {
+  const { alt } = frequencies.quality_metrics.allele_balance
+  if (!alt) {
+    return null
+  }
+
+  return alt.bin_freq[18] + alt.bin_freq[19]
+}
+
 const resolveVACohortAlleleFrequencies = async (
   obj: any,
   args: any,
@@ -382,6 +415,18 @@ const resolveVACohortAlleleFrequencies = async (
   if (!frequencies) {
     return null
   }
+  const coverage = obj.coverage[frequencyField]
+
+  const qualityMeasures = {
+    meanDepth: coverage && coverage.mean ? coverage.mean : null,
+    fractionCoverage20x: coverage && coverage.over_20 ? coverage.over_20 : null,
+    qcFilters: frequencies.filters,
+    monoallelic: frequencies.flags.includes('monoallelic'),
+    lowComplexityRegion: obj.flags.includes('lcr'),
+    lowConfidenceLossOfFunctionError: obj.flags.includes('lc_lof'),
+    lossOfFunctionWarning: obj.flags.includes('lof_flag'),
+    heterozygousSkewedAlleleCount: calculateHeterozygousSkewedAlleleCount(frequencies),
+  }
 
   const fullSet: Subset = {
     ac: frequencies.ac,
@@ -401,6 +446,7 @@ const resolveVACohortAlleleFrequencies = async (
             confidenceInterval: 0.95,
           }
         : undefined,
+    qualityMeasures,
   }
   const subsets = [fullSet, ...(frequencies.ancestry_groups as Subset[])]
   const cohortsWithoutSubcohorts = subsets.map((subset) =>

graphql-api/src/graphql/types/va.graphql

@@ -96,7 +96,6 @@ type VAQualityMeasures {
   lowComplexityRegion: Boolean
   lowConfidenceLossOfFunctionError: Boolean
   lossOfFunctionWarning: Boolean
-  noncodingTranscriptError: Boolean
   heterozygousSkewedAlleleCount: Int
 }
 
@@ -118,6 +117,8 @@ type VACohortAlleleFrequencyData {
   cohort: VACohort!
   "Ancillary results that may be associated with the CohortAlleleFrequency, providing additional context or information."
   ancillaryResults: VAAncillaryResults
+  "Metrics of quality of, or confidence in, the CohortAlleleFrequency."
+  qualityMeasures: VAQualityMeasures
   """
   A list of CohortAlleleFrequency objects describing subcohorts of the cohort currently being described.
   This creates a recursive relationship and subcohorts can be further subdivided into more subcohorts.