FSDA

FSDA analyzes cell-free DNA fragment size distributions to detect sub-chromosomal copy number variations (CNVs) in fetal genomes from maternal plasma.

Key Features:

• Fragment Size Distribution Analysis: Leverages the size distribution of cell-free DNA fragments to distinguish fetal-origin from maternal-origin DNA.
• Sub-megabase CNV Detection: Optimized to identify sub-megabase scale CNVs without relying on SNP positions.
• Detection Performance: Demonstrated perfect accuracy for 5 Mb CNVs at 13% fetal fraction, 98.82–100% detection rates at 11%, 9%, and 7% fetal fractions, and true-negative rates of 95.29–99.76%.
• Robustness Across Coverage Levels: Evaluated across sequencing coverages from 10X to 40X.

Scientific Applications:

• Non-invasive prenatal testing (NIPT): Detection of fetal aneuploidies and sub-chromosomal CNVs from maternal plasma using cfDNA fragment sizes.
• Prenatal genomic screening: Identification of sub-megabase CNVs to support earlier genetic diagnosis and potential clinical intervention during pregnancy.

Methodology:

Analyzes local distributions of cell-free DNA fragment sizes within specific genomic regions to differentiate fetal and maternal fragments and identify CNVs, validated via simulations using plasma samples with varying fetal fractions.