aa61ebc800429515f9ced7e28f669c6042219f43 max Wed Mar 18 09:09:13 2026 -0700 varFreqs supertrack: add GREGoR track, update all HTML docs, move scripts to varFreqs/, refs #36642 Add GREGoR R04 WGS track to varFreqs superTrack. Update Data Access and Methods sections for all 20+ subtrack HTML files with consistent formatting, sequencing methods from source papers, and links to makeDoc and Github scripts. Move all varFreqs conversion scripts into scripts/varFreqs/ subdirectory and update makeDoc paths accordingly. Co-Authored-By: Claude Opus 4.6 diff --git src/hg/makeDb/trackDb/human/sfariSparkExomes.html src/hg/makeDb/trackDb/human/sfariSparkExomes.html new file mode 100644 index 00000000000..e32c9ace340 --- /dev/null +++ src/hg/makeDb/trackDb/human/sfariSparkExomes.html @@ -0,0 +1,124 @@ +

Description

+The Simons Foundation Autism Research +Initiative (SFARI) 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. +

+ +

+The same frequencies shown here are also available publicly on the +SFARI Genome Browser. +See (SPARK et al, Neuron 2018) for details. +

+ +

Data Access

+The data can be explored interactively with the +Table Browser or the +Data Integrator. +For programmatic access, our REST API can be used; the +track name is sfariSparkExomes. +For bulk download, the VCF file can be obtained from +our download server. +

+Allele frequencies can also be displayed on the +SFARI Genome Browser. +Full CRAMs and VCFs with genotypes are available from +SFARI Base. +They require a data access request, which is usually reviewed quickly. More information is +available in the +SPARK Welcome Packet. +

+ +

Methods

+ +

The genome browser track project was approved by the Simons Foundation under request +number 14584.1. WES and WGS data were downloaded from +SFARI Base. +pVCFs were downloaded, anonymized with a script using bcftools and its "fill-tags" plugin and +normalized. There was no minimum allele frequency cutoff.

+ +

The methods are documented as follows by SFARI:

+ WGS: + 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 + equivalent CCDG pipeline with alignment to the GRCh38DH (1000 Genomes) + reference using BWA-MEM v0.7.15 (deterministic settings, no -M, use of + .alt contigs), Picard-equivalent duplicate marking (Picard ≥2.4.1 or + equivalent), no indel realignment, and base quality score recalibration + with GATK (dbSNP138, Mills and 1000G gold-standard indels, known + indels). Final outputs were stored as lossless CRAM files with + complete SAM-compliant read-group annotations and mandatory 4-bin + base-quality compression (Q2—6, 10, 20, 30), and all implementations + were validated for functional equivalence across centers before use. + Variant Calling was performed using DeepVariant. See + CCDG pipeline details. +
+ WES: This release contains + sequence data for 142,357 individuals and genotyping data for + 141,368 individuals. DNA was sequenced from saliva for all + samples and all participants consented to having their genetic + data shared by Regeneron. Exomes for all samples were sequenced with + short-read, paired-end sequencing of 150 bases on Illumina + NovaSeq 6000 machines using S2/S4 flow cells. Sequencing and + genotyping was performed across nine batches (WES1 through + WES9) at the Regeneron Genetics Center (RGC) and integrated + together for this data release. All sequencing batches were + processed using the same DNA extraction methods and sequencing + machines, however two different exome capture panels were used, + as described below. Genotyping was performed using a SNP + genotyping array for WES1 through WES4 and using + "genotyping-by-sequencing" (GxS) for WES5 through WES9. The + first four sequencing batches were sequenced at Regeneron using + custom NEB/Kapa reagents with the IDT (Integrated DNA + Technologies) xGen capture platform, including custom exome + capture regions. Samples starting with batch WES5 were + sequenced using the Twist Bioscience Human + Comprehensive Exome panel, combined with spike-ins for + sequencing genotyping sites (see Genotyping Methods), the full + mitochondrial genome, and coverage boosted at selected sites + for assaying clonal hematopoiesis of indeterminate potential + (CHIP). SFARI performed SNV/indel calling via DeepVariant and + GATK to generate gVCFs, pairwise relatedness inferred using + PLINK v1.9 IBD estimates from common SNPs (AF ≥ 0.01, dbSNP + v151) with ≥15% relatedness flagged, and comprehensive + individual- and family-level quality control executed using the + internal GenomeCheckMate pipeline to exclude samples based on + contamination (≥5%), insufficient coverage (<20x in <80% of + targets), sex discordance, pedigree/IBD inconsistencies, + unregistered relationships, unexpected duplicates, or excess + relatedness, after which QC-passing individuals (selecting the + most recent passing sample per person) were retained for + variant calling and joint genotyping. +

+We provide documentation that indicates how all source files of the varFreqs track were converted in the makeDoc file of the track. +For some tracks, python scripts were necessary and are also available from Github. +

+ +

References

+SPARK Consortium. Electronic address: pfeliciano@simonsfoundation.org, SPARK Consortium. + +SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research. +Neuron. 2018 Feb 7;97(3):488-493. +PMID: 29420931; PMC: PMC7444276 +