RAREsim

RAREsim simulates rare genetic variants to generate sequence-based variant datasets that mirror real sequencing data distributions for evaluation of rare-variant association methods and analysis of contributions of rare variants to complex traits and diseases.

Key Features:

• Real-Data Integration: Incorporates parameters and haplotypes derived directly from real sequencing datasets to preserve allele frequency spectra and haplotype structure.
• Accurate Variant Distribution Simulation: Simulates expected distributions of rare variants, explicitly including singletons and doubletons.
• Real-Variant Annotation Capability: Supports importation of real-variant annotations to enable in silico comparisons of rare-variant association tests and polygenic scoring approaches and to focus on putative causal variants.
• Flexibility Across Genetic Contexts: Applies across diverse genetic regions, sample sizes, ancestries, and variant classes.

Scientific Applications:

• Evaluation of rare-variant association methods: Provides realistic simulated datasets for benchmarking and comparing rare-variant association tests.
• Benchmarking polygenic scoring approaches: Enables assessment of polygenic score methods in the presence of realistic rare-variant distributions and annotations.
• Study of rare-variant contributions to complex traits: Facilitates investigation of how rare variants, including singletons and doubletons, contribute to complex trait and disease architectures.

Methodology:

Uses a simulation algorithm that leverages parameters and haplotypes from actual sequencing data, simulates rare-variant distributions including singletons and doubletons, and accepts real-variant annotations for incorporation into simulated datasets.