Optical genome mapping with whole genome sequencing identifies complex chromosomal structural variations in acute...

Area of Science:

• Genomics and Cancer Biology
• Molecular Diagnostics

Background:

• Chromosomal structural variations (SVs) are crucial in human cancer development, particularly leukemias.
• Conventional cytogenetic and molecular tools often fail to detect complex SVs accurately.

Purpose of the Study:

• To evaluate the utility of Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS) in identifying complex SVs in leukemia.
• To compare the diagnostic power of OGM and WGS against traditional methods for leukemia-associated SVs.

Main Methods:

• Five leukemia samples with known SVs were analyzed using OGM (Bionano Saphyr) and WGS.
• Copy number variation and rare variant assembly were performed using Bionano software.
• Whole genome sequencing data was analyzed for SVs using the Manta program.

Main Results:

• Leukemia samples exhibited significantly higher numbers of insertions, deletions, and inversions compared to normal samples.
• OGM and WGS successfully identified multiple complex SVs and gene fusions, including ETV6::RUNX1, BCR::ABL1, IGH::DUSP22, CBFB::MYH11, and STIL::TAL1.
• WGS precisely defined breakpoint sequences, while OGM and WGS faced challenges with pseudogene-rich regions like DUX4.

Conclusions:

• Optical Genome Mapping is a valuable tool for detecting complex SVs in leukemia, complementing G-banding analysis.
• Whole Genome Sequencing effectively resolves SV breakpoints and complements OGM findings.
• Combined OGM and WGS approaches enhance the comprehensive characterization of genomic alterations in leukemia.