Gene selection tool (GST)

Gene selection tool (GST) identifies candidate disease-associated genes from whole-exome sequencing (WES) data using multilocus variant sliding-window analyses and proportion tests for linkage-based selection.

Key Features:

• Implementation: Implemented as an R program for analysis of sequencing-derived variant lists.
• Input data: Operates on whole-exome sequencing (WES) variant calls, including single-nucleotide variants (SNVs).
• Variant model: Employs a multilocus variant approach rather than relying solely on single-locus variants (SNVs).
• Windowing approach: Sets up specific windows and uses a sliding-window methodology to observe all variants within each window.
• Statistical tests: Applies proportion tests specifically tailored for linkage analysis to evaluate candidate regions/genes.
• False-positive reduction: Designed to reduce false positives in large candidate variant lists derived from WES.
• Familial analysis: Addresses challenges from shared variants among family members in linkage/familial studies.
• Empirical validation: Successfully identified a causative gene for hereditary spastic paraplegia and additional candidate genes in a family study.

Scientific Applications:

• Linkage-based gene discovery: Prioritizes candidate genes for linkage analysis from WES data in hereditary disease studies.
• Familial variant filtering: Filters and refines variant lists in family-based studies to distinguish shared background variants from disease-associated loci.
• Case investigation: Supports identification of causative mutations in disorders such as hereditary spastic paraplegia using family-derived SNV lists.

Methodology:

Implemented in R; constructs specific windows to analyze multilocus variants using a sliding-window approach and applies proportion tests for linkage analysis to extract candidate genes from WES-derived SNV lists.