5ad55adbb6a5cc72a393700130584aa87fef2c89 lrnassar Tue Jun 30 06:15:44 2026 -0700 varFreqs: add Top 3 source AFs to mouseOvers; audit excludes SGDP and SVatalog. refs #36642 Adds a Top 3 source AFs ranking to the varFreqsAffected and varFreqsBackground mouseOvers. Alongside the pooled allele frequency, the mouseOver now lists the three cohorts/arms with the highest per-source AF, formatted as "Source (AF), Source (AF), Source (AF)". Disease cohorts with phenotype splits carry the arm label (SPARK ASD, SCHEMA case, GREGoR unaffected); population cohorts use the bare key. Per-population sub-ancestries are deliberately excluded so a high sub-pop AF cannot crowd out actual project-level signals. vcfToBigBed.py adds a top_n_source_afs helper, collects per-arm AFs into affected_arm_afs / background_arm_afs, and emits two new fields topAffectedSources and topBackgroundSources. AS schema field count 163 -> 165. An AF-distribution sweep across all 28 source cohorts identified SGDP and SVatalog as encoding allele counts per genotyped individual (small N, AF defaults near 0.5), making their per-source AF unreliable for the ranking. Adds a skip_top_ranking column (col 9) to databases.tsv, set to 1 for SGDP and SVatalog, and gates the per-arm AF append in vcfToBigBed.py on this flag. Both cohorts still contribute to pooled backgroundAC/AN/AF and still appear in backgroundSources; they are only suppressed from the Top 3. Description pages varFreqsAffected.html and varFreqsBackground.html document the ranking; the latter also documents the SGDP/SVatalog exclusion. Build documentation in varFreqs.txt is updated. diff --git src/hg/makeDb/trackDb/human/varFreqsBackground.html src/hg/makeDb/trackDb/human/varFreqsBackground.html index 5d2f82eb6ef..598b693e6ba 100644 --- src/hg/makeDb/trackDb/human/varFreqsBackground.html +++ src/hg/makeDb/trackDb/human/varFreqsBackground.html @@ -49,30 +49,59 @@ backgroundAC sums the allele counts and backgroundAN sums the allele numbers across each cohort/arm that provides both AC and AF (the per-arm AN is derived as round(AC / AF)). Two cohorts that publish only AF (ABraOM, ALFA) are still pooled by assigning them an assumed allele number, set as a default_an in the build configuration; their per-arm AC is then derived as round(AF × default_an). Cohorts that publish only AC with no default_an set (currently MGRB and the GREGoR unaffected and unknown arms), and cohorts that contribute only through per-population AC/AF (currently AllOfUs), are listed in backgroundSources but do not contribute to the pool numerator or denominator; their data remain visible in the per-database and per-population AC/AF columns. The pooled rate is preferred over a max-across-cohorts statistic so a small cohort with a high local AF (for example AllOfUs Oceanian) cannot dominate the displayed frequency.

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Top population sources by AF

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+Alongside the pooled rate, the mouseover lists the top 3 contributing +background sources ranked by their own per-source AF, formatted as +Source (AF). This surfaces population cohorts where a variant +is specifically enriched, even when the pooled rate is small; the +East-Asian founder allele +rs4986893, +for example, ranks ToMMo Japan and KOVA Korea at the top while the pooled +rate across all contributing sources sits much lower. For disease cohorts +that ship a phenotype split (SPARK, SFARI WGS, SCHEMA, GREGoR), the +displayed AF is the unaffected-arm AF and the label includes the arm (for +example SPARK non-ASD, SCHEMA ctrl); for +population cohorts, the label is the cohort name and the AF is the unified +cohort AF. Per-population sub-ancestries of a cohort (such as gnomAD +HGDP+1kG continental groups) are deliberately excluded from this ranking so +sub-population frequencies do not crowd out actual project-level signals. +

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+Two source cohorts are also excluded from the Top-3 ranking: SGDP +and SVatalog. Their VCFs encode allele counts per genotyped site +rather than per population (each variant in a single individual produces +AC=1, AN=2, AF=0.5), so the per-source AF is not a population +frequency and would always sit near the top of the ranking with a +meaningless value. Both cohorts still appear in backgroundSources +and still contribute their (small) AC and AN to the pooled +backgroundAF; they are only suppressed from the Top-3 list. +

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