FJD-pipeline

FJD-pipeline performs reanalysis of clinical exome (CE) sequencing data to increase detection of causal genetic variants and improve diagnostic yield for hereditary diseases.

Key Features:

• Variant Calling Efficiency: Detects Single Nucleotide Variants (SNVs) and Copy Number Variations (CNVs), recovering 99.74% of the causal variants identified by commercial protocols in previously solved cases.
• Enhanced Detection Capabilities: Identifies additional INDELs (insertions and deletions) and non-exonic variants that are often missed by standard commercial protocols.
• Diagnostic Yield Improvement: In re-analysis of unsolved cases, increases diagnostic yield by 2.5% in cancer cohorts and 3.2% in cardiovascular cohorts compared with commercial sequencing protocols.
• Application to Specific Genetic Disorders: Reassessed 68 inconclusive monoallelic autosomal recessive retinal dystrophy cases using reanalysis, filtering, and prioritization, yielding a 4.4% increase in diagnostic rate.
• Reanalysis Algorithm Design: Implements a reanalysis algorithm that prioritizes clinically relevant variants to optimize identification of causal mutations.

Scientific Applications:

• Clinical exome sequencing diagnostics: Augments CE sequencing as a first-tier diagnostic test for hereditary diseases by increasing detection of causal variants.
• Cancer genetics: Provides a 2.5% increase in diagnostic yield in reanalysis of cancer cohorts.
• Cardiovascular genetics: Provides a 3.2% increase in diagnostic yield in reanalysis of cardiovascular cohorts.
• Retinal dystrophy case resolution: Improves case resolution in monoallelic autosomal recessive retinal dystrophies, with a reported 4.4% diagnostic yield increase.
• Variant discovery and prioritization: Facilitates detection and prioritization of SNVs, CNVs, INDELs, and non-exonic variants relevant to hereditary disease diagnosis.

Methodology:

Uses a custom reanalysis algorithm performing variant calling for SNVs and CNVs, detection of INDELs and non-exonic variants, and filtering and prioritization of clinically relevant variants.