Deciphering the Structural Variants by Long-Read Genome Sequencing: Technology, Applications, and Case Illustrations.

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Structural variants (SVs) are large genomic alterations (>50 bp) crucial for evolution, disease, and cancer.
• Current short-read sequencing technologies (SRSs) detect less than 50% of SVs due to limitations in complex regions.
• SRSs struggle with repetitive regions, complex loci, and phasing, hindering comprehensive SV analysis.

Purpose of the Study:

• To review recent advancements in long-read sequencing (LRS) for structural variant detection.
• To highlight the capabilities of LRS platforms in characterizing diverse SVs and complex genomic regions.
• To illustrate the clinical utility of LRS in diagnosing genetic disorders.

Main Methods:

• Review of current long-read sequencing platforms (e.g., Oxford Nanopore, PacBio).
• Analysis of bioinformatic tools and data analysis strategies for LRS-based SV detection.
• Examination of validation strategies and clinical case studies.

Main Results:

• LRS technologies accurately detect a wide spectrum of SVs, including complex events.
• LRS facilitates de novo assembly, haplotype phasing, and resolution of repetitive genomic regions.
• Successful clinical diagnoses of rare diseases were achieved using LRS.

Conclusions:

• LRS significantly improves SV detection accuracy, overcoming SRS limitations.
• LRS provides deeper insights into genome disorders and aids in precise clinical diagnosis.
• Despite challenges, LRS is becoming essential for precision genomic medicine.