Integrating Optical Genome Mapping and Whole Genome Sequencing in Somatic Structural Variant Detection

Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy number changes, including deletions and duplications. Detecting structural variants is crucial for revealing their roles in tumor development, clinical outcomes, and pe...

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Bibliographic Details
Published in:Journal of personalized medicine 2024-03, Vol.14 (3), p.291
Main Authors: Budurlean, Laura, Tukaramrao, Diwakar Bastihalli, Zhang, Lijun, Dovat, Sinisa, Broach, James
Format: Article
Language:English
Subjects:
Bone marrow
Copy number
Cytogenetics
DNA
DNA sequencing
Flow cytometry
Gene mapping
Genes
Genetic analysis
Genetic diversity
Genomes
Genomics
Labeling
Molecular weight
Next-generation sequencing
Nucleotide sequencing
Patients
Pediatrics
Pharmacogenetics
Precision medicine
RNA
RNA sequencing
Spleen
Therapeutic targets
Translocation
Tumorigenesis
Whole genome sequencing
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Summary:Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy number changes, including deletions and duplications. Detecting structural variants is crucial for revealing their roles in tumor development, clinical outcomes, and personalized therapy. Presently, most studies rely on short-read data from next-generation sequencing that aligns back to a reference genome to determine if and, if so, where a structural variant occurs. However, structural variant discovery by short-read sequencing is challenging, primarily because of the difficulty in mapping regions of repetitive sequences. Optical genome mapping (OGM) is a recent technology used for imaging and assembling long DNA strands to detect structural variations. To capture the structural variant landscape more thoroughly in the human genome, we developed an integrated pipeline that combines Bionano OGM and Illumina whole-genome sequencing and applied it to samples from 29 pediatric B-ALL patients. The addition of OGM allowed us to identify 511 deletions, 506 insertions, 93 duplications/gains, and 145 translocations that were otherwise missed in the short-read data. Moreover, we identified several novel gene fusions, the expression of which was confirmed by RNA sequencing. Our results highlight the benefit of integrating OGM and short-read detection methods to obtain a comprehensive analysis of genetic variation that can aid in clinical diagnosis, provide new therapeutic targets, and improve personalized medicine in cancers driven by structural variation.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm14030291