FunVar

FunVar annotates and functionally analyzes genetic variants, particularly rare copy number variants (CNVs), to identify disrupted biological processes and mechanisms underlying complex diseases such as Autism Spectrum Disorder (ASD).

Key Features:

• Data quality improvement: Pre-processing filters exclude low-confidence CNVs to retain high-quality variant calls for downstream analysis.
• Biological process identification: Functional enrichment analysis identifies biological processes disrupted by high-quality CNVs, including nervous system development and protein polyubiquitination.
• Semantic similarity aggregation: Post-processing aggregates similar enriched biological process terms using semantic similarity to consolidate functional signals.
• Application to ASD: Applied to CNVs from individuals with Autism Spectrum Disorder (ASD), the pipeline revealed rare CNVs disrupting brain-expressed genes that dysregulate key biological processes.
• Configurability and dataset independence: The pipeline is adjustable at each step and independent of any particular dataset or software, enabling application across diverse genetic studies.

Scientific Applications:

• ASD mechanism discovery: Interpreting CNVs in ASD to reveal disrupted processes and candidate mechanistic pathways.
• Complex disease variant interpretation: Functional annotation of putative disease-causing variants in other common complex disorders to infer affected biological processes.

Methodology:

Pre-processing removes low-confidence CNVs; functional enrichment analysis identifies biological processes affected by retained CNVs; post-processing aggregates and interprets similar biological terms using semantic similarity.