Journal: Genes

Article Title: A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

doi: 10.3390/genes15070925

Figure Lengend Snippet: Run qualities and key metrics from ONT and OGM for all 9 trios.

Article Snippet: Although other works have undertaken comparisons of different short- and long-range sequencing technologies with Bionano OGM for characterisation of SVs, these have either been applied to detection of somatically arising variants in cancers [ , ] or to the detailed characterisation of individual genomes, including common SVs [ , ].

Techniques: Produced

Journal: Genes

Article Title: A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

doi: 10.3390/genes15070925

Figure Lengend Snippet: SV types and normalisation into DEL, tandem DUP, and INS events from 234 Bionano Access SV calls.

Article Snippet: Although other works have undertaken comparisons of different short- and long-range sequencing technologies with Bionano OGM for characterisation of SVs, these have either been applied to detection of somatically arising variants in cancers [ , ] or to the detailed characterisation of individual genomes, including common SVs [ , ].

Techniques:

Journal: Genes

Article Title: A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

doi: 10.3390/genes15070925

Figure Lengend Snippet: Example of DUP reclassification of an INS call made by the Bionano Access software. The figure shows the corresponding region of chromosome 1 analysed by Bionano OGM ( top ), Illumina SR-WGS ( middle ), and ONT LR-WGS ( bottom ) and aligned based on reference coordinates in hg38. In the OGM tracks, three labels of interest are highlighted for both the reference (Ref) map (labels A, B, C) and for the patient allele (Alt, labels X, Y, Z). Although an insertion of 4.7 kb of additional material is evident in the patient track, its nature is unclear because of the low resolution of OGM technology; this event was called as INS by the Bionano Access software. When assessed against the WGS data, evidence of a tandem DUP event is clearly evident in the Illumina track, where increased sequence coverage together with paired reads (green lines marking linked reads) establish its true identity. Note that increased sequence coverage is also evident in the ONT data ( bottom ), but the type of SV involved is not intuitively obvious. This SV was missed by Sniffles in Batch 1 data. Overall, it can be deduced that labels X and Y in the OGM track represent two copies of the same label due to the DUP, both corresponding to reference label A. Labels B and C map to label Z, possibly involving a dropout or merging of B and C.

Article Snippet: Although other works have undertaken comparisons of different short- and long-range sequencing technologies with Bionano OGM for characterisation of SVs, these have either been applied to detection of somatically arising variants in cancers [ , ] or to the detailed characterisation of individual genomes, including common SVs [ , ].

Techniques: Software, Sequencing

Journal: Genes

Article Title: A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

doi: 10.3390/genes15070925

Figure Lengend Snippet: The overall and per type SV detection performance of ONT and Illumina compared to Bionano OGM.

Article Snippet: Although other works have undertaken comparisons of different short- and long-range sequencing technologies with Bionano OGM for characterisation of SVs, these have either been applied to detection of somatically arising variants in cancers [ , ] or to the detailed characterisation of individual genomes, including common SVs [ , ].

Techniques:

Journal: Genes

Article Title: A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

doi: 10.3390/genes15070925

Figure Lengend Snippet: Example INS on chromosome 1 captured by ONT but not detected using Illumina WGS. Purple boxes in the ONT track ( middle panel ) clearly highlight the presence of the 2.7 kb INS, whereas Illumina short reads struggle to anchor properly owing to the size of the INS event ( top panel ). OGM was able to detect the INS ( bottom panel , blue bars represent the two patient haplotypes), but the lack of labels prevent identification of the origin of the inserted sequences.

Article Snippet: Although other works have undertaken comparisons of different short- and long-range sequencing technologies with Bionano OGM for characterisation of SVs, these have either been applied to detection of somatically arising variants in cancers [ , ] or to the detailed characterisation of individual genomes, including common SVs [ , ].

Techniques:

Journal: Frontiers in Genetics

Article Title: Optical genome mapping identifies a homozygous deletion in the non-coding region of the SCN9A gene in individuals from the same family with congenital insensitivity to pain

doi: 10.3389/fgene.2024.1375770

Figure Lengend Snippet: Optical genome mapping identified a homozygous 4.3-kb deletion, probably affecting the 5′ UTR and the first exon of the SCN9A gene (ogm[GRCh38]2q24.3(166357064_166381268)x0). Optical map of the patient in blue, and the reference of chromosome 2 in green.

Article Snippet: The 5’ variant detected using OGM has not been observed in the OGM control population (n = 179) [Bionano Solve Theory of Operation: Variant Annotation Pipeline] and has not been observed in analyses of other patients in our laboratory (n = 150).

Techniques:

Journal: Neurology: Genetics

Article Title: Identification of an 85-kb Heterozygous 4p Microdeletion With Full Genome Analysis in Autosomal Dominant Charcot-Marie-Tooth Disease

doi: 10.1212/NXG.0000000000200078

Figure Lengend Snippet: The pedigree (A) of the family and the segregation analysis (B) of each family member. (C) De novo assembly in optical genome mapping (OGM) presented a missing 85-kb fragment in affected patients. The DLE labeling sites (dark blue lines) in GRch38 reference (green contig) and 2 haplotypes (blue contigs) in S206 and S305 showed that they shared a deletion MA1 haplotype. The dashed orange lines and arrowheads denoted the position in chr4:1,707,532 and chr4:1,831,985 in their wild-type and deletion haplotypes. The orange rectangle area represents the deletion referred to the GRch38 map. (D) Linked-read WGS with phased haplotypes in the S305 trio was illustrated. RefGene showed the location of reference genes. After phased analysis, the trio haplotypes of S207 (FA, S305's father), S206 (MA, S305's mother), and S305 (PA) were shown based on variant sequencing. S206 and S305 shared the same haplotype MA1 with an 85-kb deletion, which spanned 3 genes TACC3-FGFR3-LETM1. (E) Breakpoint (BP) PCR and Sanger sequencing were performed in the S305 trio. Primers sets were designed nearby the breakpoints of the upstream (BP-left site with d85k-F1 and d85k-R1 primers) and the downstream (BP-right site with d85k-F2 and d85k-R3 primers) for wild-type allele and for deletion allele (BP junction set with d85k-F1 and d85k-R3 primers). Only the person who carried the deletion allele could be amplified by the BP-specific primer set. The results showed that S305 (PA) and S206 (MA) carried the deletion. (F) The panel showed the precise breakpoint sequencing from S305 by Sanger sequencing on the BP junction PCR product. The nucleotides in bold were the breaking sites, which resulted in the loss of an 85,106 bp fragment from chr 4:1,733,926 to chr 4:1,819,031. FA, S207; MA, S206; PA, S305; M1: 100 bp DNA ladder marker (Zymeset).

Article Snippet: HMW gDNA samples were further transferred to (1) 10x Genomics (10xG) Linked‐Read WGS on the NovaSeq 6000 Sequencing System (Illumina) with 40–60X read depth and (2) Bionano DLE optical genome mapping (OGM) on the Bionano Saphyr system (Bionano Genomics) with 60X coverage.

Techniques: Labeling, Variant Assay, Sequencing, Amplification, Marker