CWAS-Plus

CWAS-Plus estimates category-wide association of rare noncoding variation from whole-genome sequencing data by integrating user-provided functional data, facilitating identification of noncoding variant associations in genomic disorders.

Key Features:

• Whole-genome sequencing integration: Employs whole-genome sequencing data to enhance noncoding variant analysis with faster and more efficient execution of the category-wide association testing workflow.
• Functional data integration: Integrates user-provided functional datasets, including cell-type-specific functional data, to enable analysis at cell-type specific enhancers and promoters.
• Burden enrichment testing: Supports categorization and burden enrichment tests for efficient identification of noncoding associations.
• Multiple testing correction: Provides a novel approach for multiple testing correction to enhance reliability of results.
• Scalability: Enables scalability for processing large-scale whole-genome sequencing data.

Scientific Applications:

• Autism spectrum disorder: Identified noncoding de novo variant associations in transcription factor binding sites within conserved loci in autism spectrum disorder whole-genome sequencing data (n = 7,280).
• Alzheimer's disease: Detected rare noncoding variant associations in microglia-specific regulatory elements in Alzheimer's disease whole-genome sequencing data (n = 1,087).
• Cell-type-specific regulatory analysis: Facilitates noncoding variant analysis at cell-type specific enhancers and promoters using single-nuclei assay for transposase-accessible chromatin with sequencing data.

Methodology:

CWAS-Plus is adapted from a Python package for category-wide association testing (CWAS) and employs both whole-genome sequencing and user-provided functional data to enhance noncoding variant analysis.