3180d71425ab40bc022712bb95868bfe80747375
max
  Fri May 29 08:52:38 2026 -0700
[Claude] varFreqs: split SPARK+SCHEMA by phenotype, add disease + array combined tracks, drop array cohorts from varFreqsAll

#Preview2 week - bugs introduced now will need a build patch to fix
Split SFARI SPARK WES and WGS by autism status using fill-tags -S with the
SPARK individuals_registration TSV (AC_AUT / AN_AUT / AF_AUT plus
AC_NON_AUT / AN_NON_AUT / AF_NON_AUT). Added matching SCHEMA case/control
sums (AC_CASE etc.). Two new combined bigBed tracks: varFreqsDisease
(SPARK, SFARI WGS, TOPMed, SCHEMA, GREGoR, GA4K) and varFreqsArray (TPMI,
MexBB, UKBB). TPMI and MexBB are removed from varFreqsAll so the main
combined track is purely WGS/WES.

Build scripts parameterized so the same code drives all three combined
builds: mergeAndAnnotate.sh gains --databases / --tag, vcfToBigBed.py
gains --databases-file / --populations-file and a per-track autoSql table
name. mergeAndAnnotate.sh now pins /cluster/software/src/bcftools-1.22 in
PATH (--unify-chr-names is a 1.22 feature; conda's 1.14 silently fails).

refs #36642

diff --git src/hg/makeDb/trackDb/human/sfariSparkExomes.html src/hg/makeDb/trackDb/human/sfariSparkExomes.html
index f3428e3fa2a..5a710f64574 100644
--- src/hg/makeDb/trackDb/human/sfariSparkExomes.html
+++ src/hg/makeDb/trackDb/human/sfariSparkExomes.html
@@ -1,54 +1,76 @@
 <h2>Description</h2>
 <p>
 The <a href="https://sparkforautism.org/" target="_blank">Simons Foundation Autism Research
 Initiative (SFARI)</a> recruited a large cohort of families with autistic children who provided
 DNA samples and phenotypes. 54,558 families, parents and their children were sequenced, a total
 of 142,357 individuals with whole-exome (WES) and 12,519 with whole-genome sequencing (WGS).
 The data contains 32,559 trios and 8,895 quads (one sibling without autism), and 824 twins.
 </p>
 
 <p>
 The same frequencies shown here are also available publicly on the
 <a href="https://genomes.sfari.org/" target="_blank">SFARI Genome Browser</a>.
 See (SPARK et al, Neuron 2018) for details.
 </p>
 
+<h3>Phenotype-stratified counts</h3>
+<p>
+In addition to the overall allele count (AC), allele number (AN), and allele
+frequency (AF), each variant record carries counts split by autism status
+(the <tt>asd</tt> column of the SPARK individual registration file):
+</p>
+<ul>
+  <li><tt>AC_AUT</tt>, <tt>AN_AUT</tt>, <tt>AF_AUT</tt> &mdash; individuals
+      coded as autistic (<tt>asd=TRUE</tt>).</li>
+  <li><tt>AC_NON_AUT</tt>, <tt>AN_NON_AUT</tt>, <tt>AF_NON_AUT</tt> &mdash;
+      individuals coded as non-autistic (<tt>asd=FALSE</tt>); these are
+      mostly parents and unaffected siblings of the probands.</li>
+</ul>
+<p>
+A small minority of samples have a blank <tt>asd</tt> value and so contribute
+only to the overall AC/AN/AF, not to either group total.
+</p>
+
 <h2>Data Access</h2>
 <p>
 Due to license restrictions, the data for this track cannot be downloaded from the UCSC
 Genome Browser. The Table Browser, Data Integrator, and download server are not available
 for this track.
 </p>
 <p>
 Allele frequencies can also be displayed on the
 <a href="https://genomes.sfari.org/" target="_blank">SFARI Genome Browser</a>.
 Full CRAMs and VCFs with genotypes are available from
 <a href="https://base.sfari.org/" target="_blank">SFARI Base</a>.
 They require a data access request, which is usually reviewed quickly. More information is
 available in the
 <a href="https://cohorts-cdn.simonsfoundation.org/spark/researcher_packets/SPARK_SFARI_Researcher_Welcome_Packet.pdf"
 target="_blank">SPARK Welcome Packet</a>.
 </p>
 
 <h2>Methods</h2>
 
 <p>The genome browser track project was approved by the Simons Foundation under request
 number 14584.1. WES and WGS data were downloaded from
 <a href="https://base.sfari.org/" target="_blank">SFARI Base</a>.
 pVCFs were downloaded, anonymized with a script using bcftools and its &quot;fill-tags&quot; plugin and
-normalized. There was no minimum allele frequency cutoff.</p>
+normalized. There was no minimum allele frequency cutoff.
+The ASD-status sample-group file derived from the SPARK <tt>individuals_registration</tt>
+TSV was passed to fill-tags via its <tt>-S</tt> option, which adds the per-group
+<tt>AC_AUT</tt>/<tt>AN_AUT</tt>/<tt>AF_AUT</tt> and <tt>AC_NON_AUT</tt>/<tt>AN_NON_AUT</tt>/<tt>AF_NON_AUT</tt>
+tags alongside the overall AC/AN/AF.</p>
 
 <p>The methods are documented as follows by SFARI:</p>
 <ul>
   <li>
     <b>WGS</b>:
     This release consists of sequence and variant call data for 12,519
     unique individuals, of which 12,517 (99.98%) have available genome-wide
     SNP genotype data. Sequencing and genotyping of all samples in this
     release was performed at New York Genome Center (NYGC). DNA from saliva
     samples were extracted and prepared with PCR-free methods and sequenced
     with paired-end sequencing of 150 bases on the Illumina NovaSeq 6000
     system. Alignment of reads to the human reference genome version
     GRCh38, duplicate read marking, and Base Quality Score Recalibration
     (BQSR) were performed by New York Genome Center (NYGC). Whole-genome
     sequencing data were processed using a standardized, functionally