A 3D genome atlas of genetic variants and their pathological effects

Li, M.; Tang, L.

doi:10.1101/2022.11.27.518071

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bioRxiv · 10.1101/2022.11.27.518071

A 3D genome atlas of genetic variants and their pathological effects

Li, M.·Tang, L.

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Abstract

The spatial architecture of the genome can be categorized into distinct layers. Each layer plays a critical role in transcriptional regulation and/or genomic integrity. Alterations at any level of the 3D genome can lead to an unwanted cascade of molecular events, which may ultimately drive the manifestation of disease. However, a comprehensive atlas of the mutations and structural genetic defects that affect genome organization has yet to be compiled. Moreover, we lack a centralized resource for interpretating the pathological effects of such genetic mutations. Therefore, we curated from the literature all the pathological alterations from the chromosome level on down to single nucleotide polymorphisms (SNPs) in order to investigate these diverse genetic mutations. Using a two-phase scoring algorithm, 3DFunc, we scored the transcriptomic causality of all variants in the context of 3D genome architecture from 20 cancer and 15 normal tissues. Further, 3DFunc can identify pathological variant-gene pairs in non-oncological diseases. Finally, we constructed a web-based database, 3DGeOD (https://www.csuligroup.com/3DGeOD/home), to provide all the curated variants, genomic disruptions, as well as the scoring results derived from 3DFunc. In summary, our study constructed a 3D genome atlas of genetic variants and will serve as a valuable resource for mining the putative pathological effects of any genetic mutation.

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Li, M., Tang, L.. 2022-11-27. A 3D genome atlas of genetic variants and their pathological effects. https://doi.org/10.1101/2022.11.27.518071

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