小柯机器人

新方法可有效利用Hi-C数据发掘染色质相互作用
2022-07-13 14:34

美国凯斯西储大学Fulai Jin、Yan Li、Jing Li课题组合作发现,DeepLoop可以千碱基分辨率从稀疏等位基因解析或单细胞Hi-C数据中发掘染色质相互作用。相关论文于2022年7月11日发表于国际学术期刊《自然-遗传学》。

在本研究中,研究人员研发了DeepLoop,它可以严格的校正偏差,然后执行基于深度学习的信号增强,以从低深度Hi-C数据中进行有效的染色质相互作用映射。DeepLoop支持循环分辨率、单细胞Hi-C分析。它还能识别不同Hi-C程序以及与微球菌核酸酶(micro-C)之间的跨平台融合。DeepLoop有利于研究人员发现人类基因组中等位基因特异性染色质相互作用的遗传和表观遗传决定因素。研究还发现了受印记或等位基因DNA甲基化控制的等位基因特异性相互作用新位点。

研究人员还发现,在失活X染色体(Xi)中,DXZ4 'megadomain' 边界处的局部环可逃避X失活,但FIRRE 'superloop' 基因座并没有。重要的是,DeepLoop可以揭示导致等位基因染色质环的杂合单核苷酸多态性和大型结构变体,其中许多是由重新连接增强子并产生转录造成的。总之,DeepLoop扩展了Hi-C的使用,实现了对三维基因组遗传学的循环解析。

研究人员表示,利用嘈杂Hi-C热图绘制染色质环仍面临重大挑战。

附:英文原文

Title: DeepLoop robustly maps chromatin interactions from sparse allele-resolved or single-cell Hi-C data at kilobase resolution

Author: Zhang, Shanshan, Plummer, Dylan, Lu, Leina, Cui, Jian, Xu, Wanying, Wang, Miao, Liu, Xiaoxiao, Prabhakar, Nachiketh, Shrinet, Jatin, Srinivasan, Divyaa, Fraser, Peter, Li, Yan, Li, Jing, Jin, Fulai

Issue&Volume: 2022-07-11

Abstract: Mapping chromatin loops from noisy Hi-C heatmaps remains a major challenge. Here we present DeepLoop, which performs rigorous bias correction followed by deep-learning-based signal enhancement for robust chromatin interaction mapping from low-depth Hi-C data. DeepLoop enables loop-resolution, single-cell Hi-C analysis. It also achieves a cross-platform convergence between different Hi-C protocols and micrococcal nuclease (micro-C). DeepLoop allowed us to map the genetic and epigenetic determinants of allele-specific chromatin interactions in the human genome. We nominate new loci with allele-specific interactions governed by imprinting or allelic DNA methylation. We also discovered that, in the inactivated X chromosome (Xi), local loops at the DXZ4 ‘megadomain’ boundary escape X-inactivation but the FIRRE ‘superloop’ locus does not. Importantly, DeepLoop can pinpoint heterozygous single-nucleotide polymorphisms and large structure variants that cause allelic chromatin loops, many of which rewire enhancers with transcription consequences. Taken together, DeepLoop expands the use of Hi-C to provide loop-resolution insights into the genetics of the three-dimensional genome.

DOI: 10.1038/s41588-022-01116-w

Source: https://www.nature.com/articles/s41588-022-01116-w

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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