POSTRE

POSTRE predicts the pathogenic effects of structural variants on coding sequences and non-coding regulatory elements by integrating disease-relevant cellular contexts to evaluate changes in enhancer dosage and long-range enhancer–gene communication relevant to human congenital disorders.

Key Features:

• Supported SV types: Evaluates deletions, duplications, inversions, and translocations for their impact on coding and non-coding regions.
• Pathogenicity prediction: Predicts the pathogenicity of structural variants implicated in human congenital disorders.
• Disease-context integration: Integrates disease-relevant cellular contexts into analyses to improve specificity and sensitivity of SV interpretation.
• Regulatory element analysis: Analyzes non-coding regulatory elements such as enhancers, including assessment of enhancer dosage and long-range enhancer–gene communication.
• Mechanism inference: Predicts candidate disease genes and infers pathogenic mechanisms including gene deletion, enhancer disconnection, and enhancer adoption.
• Coding versus regulatory effects: Identifies SVs causing direct coding disruption as well as long-range regulatory consequences.

Scientific Applications:

• SV interpretation in congenital disorders: Prioritizes and interprets structural variants affecting enhancers and coding regions in human congenital disorders.
• Gene nomination and mechanism elucidation: Nominates candidate disease genes and elucidates mechanisms such as gene deletion, enhancer disconnection, or enhancer adoption.
• Mechanistic research and diagnosis: Informs mechanistic studies of how non-coding SVs alter gene expression in disease-relevant cellular contexts and supports genetic diagnosis efforts.

Methodology:

Integrates disease-relevant cellular contexts and analyzes enhancer dosage and long-range enhancer–gene communication to predict SV pathogenicity and infer mechanisms including gene deletion, enhancer disconnection, and enhancer adoption.