GCfix: a fast and accurate fragment length-specific method for correcting GC bias in cell-free DNA

Area of Science:

• Bioinformatics
• Genomics
• Molecular Biology

Background:

• Cell-free DNA (cfDNA) analysis offers noninvasive clinical applications.
• GC bias complicates cfDNA fragmentomics and copy number analysis.
• Existing GC correction methods lack standardization and rigorous validation for cfDNA data.

Purpose of the Study:

• To develop and validate a robust GC bias correction method for cfDNA data.
• To introduce standardized metrics for evaluating GC bias correction effectiveness.
• To address the need for accurate cfDNA analysis across diverse coverage levels.

Main Methods:

• Developed GCfix, a fast and accurate GC bias correction method for cfDNA.
• Conducted in-depth analysis of cfDNA GC bias at region and fragment length levels.
• Introduced two orthogonal metrics to assess GC bias correction performance.

Main Results:

• GCfix effectively corrects GC bias in cfDNA data across various coverages.
• GCfix outperforms existing cfDNA GC bias correction methods based on introduced metrics.
• Generated correction factors, tagged BAM files, and corrected coverage tracks.

Conclusions:

• GCfix provides a robust solution for GC bias correction in cfDNA analysis.
• The developed metrics enable standardized comparison of GC bias correction methods.
• GCfix enhances the reliability of cfDNA fragmentomics and copy number analysis.