ClinTAD

ClinTAD integrates copy number variants (CNVs) with topologically associated domains (TADs) to evaluate their potential clinical relevance by assessing gene content and Human Phenotype Ontology (HPO)-based genotype–phenotype correlations.

Key Features:

• Integration of chromatin architecture: Maps CNVs to TADs to evaluate potential effects of CNVs on chromatin organization beyond protein-coding gene disruption.
• Clinical interpretation enhancement: Assesses CNVs, including variants of uncertain clinical significance (VUS), in the context of nearby TADs to inform pathogenicity hypotheses.
• Phenotype correlation: Utilizes Human Phenotype Ontology (HPO) annotations to determine whether genes within disrupted TAD boundaries correlate with observed patient phenotypes.

Scientific Applications:

• CNV evaluation from SNP microarray: Applied to CNVs identified through single-nucleotide polymorphism (SNP) microarray analysis to provide TAD-aware interpretation.
• Cohort comparison of VUS and benign variants: Used in a study of 209 cases with 236 CNVs to compare VUS versus benign variants, revealing a higher proportion of VUS associated with TADs linked to patient phenotypes.

Methodology:

Maps CNV coordinates to TADs and evaluates gene content within disrupted TAD boundaries, using Human Phenotype Ontology (HPO) annotations to correlate genes with patient phenotypes.