TADeus-a tool for clinical interpretation of structural variants modifying chromatin organization

Chromosomal rearrangements spanning non-coding regions may convey an abnormal phenotype by various position effects. Alterations in chromosome structure can disrupt interactions between gene promoters and their regulatory elements or place genes in an inappropriate chromosomal domain. Evaluation of the impact of such genomic aberrations on gene expression has been often neglected, especially when other structural variants (SVs) affecting genes are detected. Another reason for not considering such rearrangements has been the lack of appropriate methods or tools to visualize and prioritize the neighboring genes according to their clinical relevance.To address these challenges, we developed TADeus, an easy-to-use open-source web application dedicated for clinical evaluation of variants in genes whose expression may be affected by chromosomal rearrangements. The main functionality of TADeus provides a view of regulatory landscape of regions surrounding breakpoints of the rearrangements by combing chromatin conformation data (Hi-C) with other omics data. TADeus prioritizes genes using number of interrupted enhancer-promoter interactions, the distance from the breakpoints, the phenotypic data, and haploinsufficiency scores. In addition, TADeus can serve as a genomic browser that shows Hi-C matrices with one-dimensional genomic data and allows users to compare Hi-C data from different tissues.

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