Genome Center, UC Davis, Davis, USA.
UC Davis MIND Institute, Sacramento, USA.
Genome Biol. 2019 Mar 21;20(1):60. doi: 10.1186/s13059-019-1666-7.
Deletions that fuse two adjacent topologically associating domains (TADs) can cause severe developmental disorders. We provide a formal method to quantify deletions based on their potential disruption of the three-dimensional genome structure, denoted as the TAD fusion score. Furthermore, we show that deletions that cause TAD fusion are rare and under negative selection in the general population. Finally, we show that our method correctly gives higher scores to deletions reported to cause various disorders, including developmental disorders and cancer, in comparison to the deletions reported in the 1000 Genomes Project. The TAD fusion score tool is publicly available at https://github.com/HormozdiariLab/TAD-fusion-score .
融合两个相邻拓扑关联域 (TAD) 的缺失可导致严重的发育障碍。我们提供了一种正式的方法，根据其对三维基因组结构的潜在破坏程度，对缺失进行量化，记为 TAD 融合评分。此外，我们表明，导致 TAD 融合的缺失在普通人群中是罕见的，并且受到负选择的影响。最后，我们表明，与 1000 基因组计划中报道的缺失相比，我们的方法正确地给予了更高的评分给那些报道可导致各种疾病（包括发育障碍和癌症）的缺失。TAD 融合评分工具可在 https://github.com/HormozdiariLab/TAD-fusion-score 上公开获取。
