SHaploseek: A sequencing-only high-resolution implementation of comprehensive preimplantation genetic testing
Backenroth, D.; Altarescu, G.; Zahdeh, F.; Mann, T.; Murik, O.; Renbaum, P.; Segel, R.; Zeligson, S.; Hakam-Spector, E.; Carmi, S.; Zeevi, D. A.
Show abstract
PurposeWe previously developed Haploseek, a clinically-validated, variant-agnostic comprehensive preimplantation genetic testing (PGT) solution. Haploseek is based on microarray genotyping of the embryos parents and relatives, combined with low-pass sequencing of the embryos. Here, to increase throughput and versatility, we aimed to develop a sequencing-only implementation of Haploseek. MethodsWe developed SHaploseek, a universal PGT method to determine genome-wide haplotypes of each embryo based on low-pass ([≤]5x) sequencing of the parents and relative(s) along with ultra-low pass (0.2-0.4x) sequencing of the embryos. We used SHaploseek to analyze five single lymphoblast cells and 31 embryos from 14 families. We validated the genome-wide haplotype predictions against either bulk DNA, Haploseek, or, at focal genomic sites, PCR-based PGT results. ResultsSHaploseek achieved >99% concordance with bulk DNA in two families from which single cells were derived from grown-up children. In embryos from 12 PGT families, all of SHaploseeks focal site haplotype predictions were concordant with clinical PCR-based PGT results. Genome-wide, there was >99% median concordance between Haploseek and SHaploseeks haplotype predictions. Concordance remained high at all assayed sequencing depths [≥]2x, as well as with only 1ng of parental DNA input. In subtelomeric regions, significantly more haplotype predictions were high-confidence in SHaploseek compared to Haploseek. ConclusionAs a single-platform comprehensive PGT solution with higher sensitivity in subtelomeric regions, SHaploseek constitutes a significantly improved, accurate, and cost-effective re-embodiment of Haploseek.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Long read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits 95%
- Inferring compound heterozygosity from large-scale exome sequencing data 95%
- Efficient phasing and imputation of low-coverage sequencing data using large reference panels 94%
Similar papers in this journal
- Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection 95%
- A survey of rare epigenetic variation in 23,116 human genomes identifies disease-relevant epivariations and novel CGG expansions 94%
- HiFi long-read genomes for difficult-to-detect clinically relevant variants 94%
Similar papers in this journal
- Genetic Diagnosis of Facioscapulohumeral Muscular Dystrophy Type 1 Using Rare Variant Linkage Analysis and Long Read Genome Sequencing 93%
- 3-hour genome sequencing and targeted analysis to rapidly assess genetic risk 93%
- The impact of the Turkish (TK) population variome on the genomic architecture of rare disease traits 93%
Similar papers in this journal
- Long-read genome sequencing for the diagnosis of neurodevelopmental disorders 94%
- Leveraging TOPMed Imputation Server and Constructing a Cohort-Specific Imputation Reference Panel to Enhance Genotype Imputation among Cystic Fibrosis Patients 94%
- Omics-informed CNV calls reduce false positive rate and improve power for CNV-trait associations 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.