Successful optical genome mapping from 500 000 cells: A low-input UHMW DNA extraction approach

Area of Science:

• Genomics
• Molecular Biology
• Clinical Diagnostics

Background:

• Optical Genome Mapping (OGM) is crucial for detecting DNA variations in hematological malignancies.
• Isolating ultra-high molecular weight genomic DNA (UHMW gDNA) for OGM typically requires 1.5 million cells.
• Clinical samples, like those from multiple myeloma patients, often have fewer than the required cells.

Purpose of the Study:

• To develop a customized protocol for isolating UHMW gDNA from a reduced cell input.
• To enable OGM analysis from limited clinical samples, such as CD138-positive cells from bone marrow aspirates.
• To ensure sufficient DNA quality and quantity for comprehensive OGM data generation.

Main Methods:

• A modified protocol was developed for UHMW gDNA isolation.
• The protocol was optimized for starting with as few as 500,000 cells.
• DNA quality and quantity were assessed for downstream OGM analysis.

Main Results:

• Successful isolation of UHMW gDNA from 500,000 cells was achieved.
• The isolated DNA was of sufficient quality and quantity for OGM.
• At least 1500 Gbp of OGM data could be collected from the prepared DNA.

Conclusions:

• The developed protocol significantly reduces the cell input requirement for UHMW gDNA isolation.
• This method expands the applicability of OGM in clinical settings, particularly for samples with limited cell numbers.
• The protocol facilitates advanced genomic analysis for hematological malignancies, improving diagnostic capabilities.