Comparison of Capture Hi-C Analytical Pipelines.
Comparison of Capture Hi-C Analytical Pipelines.
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DOI：
10.3389/fgene.2022.786501
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发表时间：
2022
影响因子：
3.7
通讯作者：
Mifsud B
中科院分区：
文献类型：
--
作者：
Aljogol D;Thompson IR;Osborne CS;Mifsud B
现在很明显，DNA形成了一个有组织的核结构，这对维持基因组的结构和功能完整性至关重要。由于最近染色体构象捕获技术的蓬勃发展，可以系统地研究染色质组织（例如，3C及其后继者4C、5C和Hi-C），这伴随着计算管道的发展，以识别此类数据中具有生物学意义的染色质接触。然而，并不是所有的工具都适用于所有的实验设计和所有的结构特征。捕获Hi-C（CHi-C）是一种使用中间杂交步骤来靶向和选择Hi-C文库中预定义的感兴趣区域，从而增加这些区域的有效测序深度的方法。它允许研究人员以高分辨率研究精细的染色质结构，例如启动子-增强子环，但它在捕获步骤中引入了额外的偏差，因此需要专门的管道。在这里，我们比较了CHi-C数据分析的多个分析管道。我们考虑了保留多映射读取的效果，并比较了不同统计方法在识别可重现相互作用和确定生物学显著相互作用方面的效率。在限制性片段水平分辨率下，可以挽救的多映射读段的数量可以忽略不计。根据分析方法的不同，确定的相互作用的数量差异很大，表明I型和II型错误率存在很大差异。最佳管道取决于假阳性和假阴性染色质接触的项目特异性耐受水平。
It is now evident that DNA forms an organized nuclear architecture, which is essential to maintain the structural and functional integrity of the genome. Chromatin organization can be systematically studied due to the recent boom in chromosome conformation capture technologies (e.g., 3C and its successors 4C, 5C and Hi-C), which is accompanied by the development of computational pipelines to identify biologically meaningful chromatin contacts in such data. However, not all tools are applicable to all experimental designs and all structural features. Capture Hi-C (CHi-C) is a method that uses an intermediate hybridization step to target and select predefined regions of interest in a Hi-C library, thereby increasing effective sequencing depth for those regions. It allows researchers to investigate fine chromatin structures at high resolution, for instance promoter-enhancer loops, but it introduces additional biases with the capture step, and therefore requires specialized pipelines. Here, we compare multiple analytical pipelines for CHi-C data analysis. We consider the effect of retaining multi-mapping reads and compare the efficiency of different statistical approaches in both identifying reproducible interactions and determining biologically significant interactions. At restriction fragment level resolution, the number of multi-mapping reads that could be rescued was negligible. The number of identified interactions varied widely, depending on the analytical method, indicating large differences in type I and type II error rates. The optimal pipeline depends on the project-specific tolerance level of false positive and false negative chromatin contacts.
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影响因子：
30.8
作者：
Mifsud, Borbala;Tavares-Cadete, Filipe;Osborne, Cameron S.
通讯作者：
Osborne, Cameron S.
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
16.6
作者：
Baxter JS;Leavy OC;Dryden NH;Maguire S;Johnson N;Fedele V;Simigdala N;Martin LA;Andrews S;Wingett SW;Assiotis I;Fenwick K;Chauhan R;Rust AG;Orr N;Dudbridge F;Haider S;Fletcher O
通讯作者：
Fletcher O
影响因子：
12.3
作者：
Furlan-Magaril M;Ando-Kuri M;Arzate-Mejía RG;Morf J;Cairns J;Román-Figueroa A;Tenorio-Hernández L;Poot-Hernández AC;Andrews S;Várnai C;Virk B;Wingett SW;Fraser P
通讯作者：
Fraser P
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK