Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI:10.1038/s44320-024-00065-2
Yeonghun Lee, Sung-Hye Park, Hyunju Lee
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引用次数: 0

Abstract

The 3D genome prediction in cancer is crucial for uncovering the impact of structural variations (SVs) on tumorigenesis, especially when they are present in noncoding regions. We present InfoHiC, a systemic framework for predicting the 3D cancer genome directly from whole-genome sequencing (WGS). InfoHiC utilizes contig-specific copy number encoding on the SV contig assembly, and performs a contig-to-total Hi-C conversion for the cancer Hi-C prediction from multiple SV contigs. We showed that InfoHiC can predict 3D genome folding from all types of SVs using breast cancer cell line data. We applied it to WGS data of patients with breast cancer and pediatric patients with medulloblastoma, and identified neo topologically associating domains. For breast cancer, we discovered super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. For medulloblastoma, we found SVs in noncoding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In addition, we provide trained models for cancer Hi-C prediction from WGS at https://github.com/dmcb-gist/InfoHiC , uncovering the impacts of SVs in cancer patients and revealing novel therapeutic targets.

利用 InfoHiC 从全基因组测序预测三维癌症基因组。
癌症三维基因组预测对于揭示结构变异(SV)对肿瘤发生的影响至关重要,尤其是当结构变异存在于非编码区时。我们提出了一个系统框架 InfoHiC,用于直接从全基因组测序(WGS)预测三维癌症基因组。InfoHiC利用SV等位基因组装上的等位基因特异拷贝数编码,从多个SV等位基因进行等位基因到总Hi-C的转换,从而预测癌症Hi-C。我们利用乳腺癌细胞系数据证明,InfoHiC 可以预测所有类型 SV 的三维基因组折叠。我们将其应用于乳腺癌患者和儿童髓母细胞瘤患者的 WGS 数据,并发现了新的拓扑关联域。在乳腺癌方面,我们发现了与致癌基因过表达和不良生存结果相关的超增强子劫持事件。对于髓母细胞瘤,我们发现了非编码区中的 SV,它们导致了髓母细胞瘤驱动基因(GFI1、GFI1B 和 PRDM6)的超级增强子劫持事件。此外,我们还提供了经过训练的癌症Hi-C预测模型,这些模型来自WGS https://github.com/dmcb-gist/InfoHiC,揭示了SV对癌症患者的影响,并揭示了新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
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