+This track shows structural variants (SVs) identified by Oxford Nanopore +long-read sequencing of post-mortem brain tissue (prefrontal cortex) from +351 individuals, generated by the NIH Center for Alzheimer's and Related +Dementias (NIH CARD) Long-Read Initiative. Structural variants are genomic +rearrangements larger than about 50 bp, such as deletions, insertions, +inversions and duplications; because they alter or move large stretches of +DNA at once they can have outsized effects on gene dosage, gene regulation +and DNA methylation compared with single-nucleotide changes. +
++The cohort combines two studies: 205 samples of European ancestry from the +North American Brain Expression Consortium (NABEC, dbGaP phs001300) and 146 +samples of African and African-admixed ancestry from the NIMH Human Brain +Collection Core (HBCC, dbGaP phs000979). The track contains more than 228,000 SVs called +against GRCh38: about 127,000 insertions, 102,000 deletions, 431 inversions +and one tandem duplication. Each record carries the number of carrier samples +overall and split by cohort (NABEC and HBCC), together with the allele frequency reported +by the source project. +
+ ++Items are colored by SV type, matching the other subtracks of the container: +
+Insertions are placed at the insertion site with a width of 1 bp, and the +length of the inserted sequence is shown as the insertion length; deletions, +inversions and the duplication span the affected reference interval. The +mouseover shows the variant name, SV type, reference and insertion lengths, +allele frequency and the number of carrier samples split into the NABEC and +HBCC cohorts. Filters are available for SV type, SV length, insertion length, +carrier count, allele frequency, and the number of carriers in each cohort. +
+ ++NABEC samples were sequenced on Oxford Nanopore R9.4.1 and HBCC samples on +R10.4.1 PromethION flow cells, with a median read N50 of 27 kb and about 40x +average genome coverage. Structural variants were called both from read +alignments (minimap2 alignments processed with Sniffles2 v2.3) and from +de novo assemblies (Shasta v0.11.1 assemblies phased with HapDup v0.12 and +compared to the reference with Hapdiff). Assembly-based calls were merged +across samples with Truvari, read-based calls were merged across samples with +Sniffles2, and the read and assembly sets were then merged together and across +the two cohorts with Truvari. All processing used the Nanopore Analysis +Pipeline (NAPU) workflows on the AnVIL/Terra platform; see Kolmogorov et al. +2023 and Billingsley et al. 2024 for details. +
++The display bigBed NIH_CARD_longReadSVs.bb was obtained from the NIH +CARD browser-track +GitHub +repository. At UCSC it was converted to the shared long-read SV schema +(signed lengths made positive, an explicit insertion-length field added, the +single DUP:TANDEM call folded to DUP, and colors reassigned to +the container's shared palette) so it matches the other subtracks. The +step-by-step commands are recorded in the UCSC makeDoc for this track +container: + +doc/hg38/lrSv.txt. The conversion script and autoSql schema live in + +makeDb/scripts/lrSv, and the track configuration is in +trackDb/human/lrSv.ra. +
+ ++The data can be explored interactively in table format with the +Table Browser or the +Data Integrator and exported from there +to spreadsheet or tab-sep tables. From scripts, the data can be accessed +through our API, track=cardSv. +
++The annotation is stored as a bigBed file that can be downloaded from +our +download server as card.bb. Individual regions or the whole +annotation can be obtained with the bigBedToBed utility, available +from our +utilities +page. Example: +bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/lrSv/card.bb -chrom=chr21 -start=0 -end=100000000 stdout. +
++The underlying genotype-level calls in VCF format are available under +controlled access through dbGaP (NABEC phs001300, substudy phs003181; HBCC +phs000979) and can be requested through the AnVIL Data Explorer for the +NABEC +and +HBCC +datasets. +
+ ++Thanks to the North American Brain Expression Consortium (NABEC), the NIMH +Human Brain Collection Core (HBCC), the Banner Sun Health Research Institute +Brain and Body Donation Program, and the NIH CARD Long-Read Initiative for +generating and sharing this dataset, and to Melissa Meredith for preparing the +browser track. This work was supported by the Intramural Research Programs of +the NIA, NINDS, NCI, NHGRI and NIMH, and used the NIH STRIDES Initiative and +the NIH HPC Biowulf cluster. +
+ ++Billingsley KJ, Meredith M, Daida K, Jerez PA, Negi S, Malik L, Genner RM, Moller A, Zheng X, Gibson +SB et al. + +Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural +variation on gene expression and DNA methylation. +bioRxiv. 2024 Dec 17;. +PMID: 39764002; PMC: PMC11702628 +
+ + + ++Kolmogorov M, Billingsley KJ, Mastoras M, Meredith M, Monlong J, Lorig-Roach R, Asri M, Alvarez +Jerez P, Malik L, Dewan R et al. + +Scalable Nanopore sequencing of human genomes provides a comprehensive view of haplotype-resolved +variation and methylation. +Nat Methods. 2023 Oct;20(10):1483-1492. +PMID: 37710018; PMC: PMC11222905 +
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