HiCHap: a package to correct and analyze the diploid Hi-C data.

HiCHap: a package to correct and analyze the diploid Hi-C data.
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HICHAP:纠正和分析二倍体HI-C数据的软件包。

DOI:
10.1186/s12864-020-07165-x
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发表时间:
2020-10-27
期刊:
影响因子:
4.4
通讯作者:
Peng C
Peng C
中科院分区:
生物学2区
文献类型:
--
作者:
Luo H;Li X;Fu H;Peng C

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在二倍体细胞中,重要的是分别构建母本和父本Hi-C接触图,因为两个同源染色体在染色质三维(3D)组织中可能不同。以往的软件虽然可以利用定相遗传变异构建二倍体(母本和父本)Hi-C接触图谱,但都忽略了基因组中变异密度不同所导致的二倍体Hi-C接触图谱的系统性偏差。此外,还没有软件对等位基因特异性的染色质三维结构(包括区室、拓扑结构域和染色质环)进行定量分析。本研究揭示了二倍体Hi-C接触图谱中由变异密度引起的等位基因分配偏差的特征,并提出了一种新的校正策略。基于偏倚校正,我们开发了一个集成工具,称为HiCHap,用于执行读段作图,接触图构建,全基因组鉴定隔室,拓扑结构域和染色质环,以及二倍体Hi-C数据的等位基因特异性测试。我们的研究结果表明,在HiCHap等位基因分配偏差的校正显着提高二倍体Hi-C接触图的质量,随后促进二倍体染色质3D组织的全基因组鉴定,包括区室,拓扑结构域和染色质环。最后,HiCHap还支持不区分两个同源染色体的单倍体Hi-C图谱的数据分析。我们提供了一个集成的软件包HiCHap,用于对二倍体Hi-C数据进行数据处理、偏倚校正和结构分析。HiCHap软件的源代码和教程可在https://pypi.org/project/HiCHap/免费获得。在线版本包含补充材料,可通过10.1186/s12864-020-07165-x获得。
In diploid cells, it is important to construct maternal and paternal Hi-C contact maps respectively since the two homologous chromosomes can differ in chromatin three-dimensional (3D) organization. Though previous softwares could construct diploid (maternal and paternal) Hi-C contact maps by using phased genetic variants, they all neglected the systematic biases in diploid Hi-C contact maps caused by variable genetic variant density in the genome. In addition, few of softwares provided quantitative analyses on allele-specific chromatin 3D organization, including compartment, topological domain and chromatin loop. In this work, we revealed the feature of allele-assignment bias caused by the variable genetic variant density, and then proposed a novel strategy to correct the systematic biases in diploid Hi-C contact maps. Based on the bias correction, we developed an integrated tool, called HiCHap, to perform read mapping, contact map construction, whole-genome identification of compartments, topological domains and chromatin loops, and allele-specific testing for diploid Hi-C data. Our results show that the correction on allele-assignment bias in HiCHap does significantly improve the quality of diploid Hi-C contact maps, which subsequently facilitates the whole-genome identification of diploid chromatin 3D organization, including compartments, topological domains and chromatin loops. Finally, HiCHap also supports the data analysis for haploid Hi-C maps without distinguishing two homologous chromosomes. We provided an integrated package HiCHap to perform the data processing, bias correction and structural analysis for diploid Hi-C data. The source code and tutorial of software HiCHap are freely available at https://pypi.org/project/HiCHap/. The online version contains supplementary material available at 10.1186/s12864-020-07165-x.
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