Copy-Number Variants Detection by Low-Pass Whole-Genome Sequencing

Area of Science:

• Genomics
• Clinical Diagnostics
• Bioinformatics

Background:

• Whole-genome sequencing (WGS) shows promise for copy-number variant (CNV) detection, outperforming chromosomal microarray analysis (CMA) in certain genomic regions.
• Current limitations of WGS for clinical application include high costs, extended turnaround times, and significant computational resource demands.
• These factors hinder the routine integration of WGS into standard clinical laboratory workflows.

Purpose of the Study:

• To describe a novel protocol for CNV detection using low-pass WGS (0.25×) suitable for a clinical laboratory setting.
• To address the economic and logistical barriers associated with WGS implementation in routine diagnostics.
• To establish a clinically viable method for CNV analysis with reduced costs and faster processing.

Main Methods:

• Development and validation of a low-pass (0.25×) whole-genome sequencing protocol.
• Implementation of the protocol within a clinical laboratory environment.
• Assessment of cost-effectiveness and turnaround time for CNV detection.

Main Results:

• The developed protocol enables CNV detection from low-pass WGS data.
• The cost per sample is reduced to under $200 USD.
• The turnaround time is reduced to within 7 days, meeting clinical requirements.

Conclusions:

• The described protocol offers a cost-effective and time-efficient solution for CNV detection using low-pass WGS.
• This approach facilitates the clinical integration of WGS for genetic diagnostics.
• The method provides a practical alternative to CMA for CNV analysis in a clinical setting.