LoFTK

LoFTK predicts and annotates loss-of-function (LoF) variants in human genomes to identify affected genes and the number of gene copies impacted.

Key Features:

• Automated Prediction: Processes variants from both genotyped and sequenced genomes to automate LoF variant prediction.
• High-confidence LoF Prediction: Predicts high-confidence loss-of-function (LoF) variants.
• Gene Inactivity Identification: Identifies genes that are inactive in one or two copies to report gene-level copy impact.
• Compound Heterozygous (CH) Variant Detection: Detects CH LoF variants that result in loss of function across both gene copies.
• Summary Statistics: Generates summary statistics to support downstream analyses.

Scientific Applications:

• Clinical phenotype studies: Supports studies of clinical phenotypes associated with LoF variants by identifying affected genes and copy number status.
• Inheritance and CH variant analysis: Enables investigation of compound heterozygosity and inheritance patterns using parent–offspring genomic data.
• Basic and applied genomic research: Provides detailed variant- and gene-level LoF information for basic research and applied clinical investigations.

Methodology:

Processes genotyped and sequenced genomic data and leverages parental and offspring genomic data to identify compound heterozygous LoF genes, with 96% of predicted CH LoF genes in offspring showing respective allele donation from each parent.