JAX-CNV

JAX-CNV detects copy number variations (CNVs) from whole-genome sequencing (WGS) data to provide high-sensitivity CNV calling for clinical and research applications.

Key Features:

• Whole-Genome Sequencing Integration: Analyzes WGS data to identify copy number variations (CNVs).
• Sensitivity and Recall: Demonstrated 100% recall of clinically validated CNVs in a blinded evaluation of 31 samples and detected an average of 30 CNVs per individual (~seven-fold increase over chromosomal microarrays).
• False Discovery Rate: Experimental validation of 24 randomly selected CNVs produced one false positive (FDR 4.17%).
• Coverage-Resilience: Maintains high sensitivity for CNVs >300 kb at 10× coverage and reports sensitivities for CNVs >50 kb of 100% at >20×, 97% at 15×, and 95% at 10×.
• Clinical Applicability: Performance indicates potential to replace chromosomal microarrays (CMAs) as a first-tier genetic test pending further multi-institutional validation.

Scientific Applications:

• Clinical CNV Detection: Enables identification of clinically relevant CNVs from WGS, improving diagnostic yield compared with chromosomal microarrays.
• CNV Discovery and Research: Detects a larger set of CNVs per individual, supporting studies of genomic structural variation and its clinical relevance.

Methodology:

Implements a WGS-based CNV calling algorithm and was benchmarked by blinded comparison to clinically validated chromosomal microarray (CMA) results with sensitivity assessments across multiple sequencing coverages.