RUTH

RUTH performs robust tests of Hardy-Weinberg Equilibrium (HWE) for sequence-based genotypes across diverse ancestries by integrating principal components and genotype uncertainty to adjust for population structure.

Key Features:

• Population-structure adjustment: Integrates genotype data and principal components to adjust HWE tests for population structure.
• Genotype uncertainty handling: Accounts for genotype uncertainty inherent in sequence-based genotypes when estimating HWE deviation.
• Statistical tests implemented: Implements both a likelihood ratio test and a score test to estimate deviation from HWE.
• Comparison to standard tests: Addresses limitations of standard χ² and exact HWE tests that can produce inflated false positives in heterogeneous populations.
• Input format support: Supports standard VCF/BCF file formats for genotype data input.
• Scalability: Enables testing across millions of genetic markers and hundreds of thousands of individuals for large-scale genomic datasets.
• Empirical validation: Evaluated on simulated and real sequence datasets to assess false positive rates and statistical power.

Scientific Applications:

• Genotype quality assessment: Detects deviations from HWE indicative of technical artifacts or incorrect genotype calls.
• Population genetics studies: Performs HWE testing in studies involving diverse ancestries and structured populations.
• Assessment of population-structure effects: Quantifies the impact of ancestry and population structure on HWE metrics.
• Large-scale variant screening: Enables HWE-based filtering across large genomic datasets in sequence-based studies.

Methodology:

Integrates genotypes with principal components, accounts for genotype uncertainty, and employs either a likelihood ratio test or a score test on VCF/BCF-formatted sequence data; evaluated using simulated and real sequence datasets.