Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is a critical part of most Hi-C analyses. However, current methods often miss visually evident CTCF loops in Hi-C data sets from mammals, and they completely fail to identify high intensity loops in other organisms. We present SIP, Significant Interaction Peak caller, and SIPMeta, which are platform independent programs to identify and characterize these loops in a time- and memory-efficient manner. We show that SIP is resistant to noise and sequencing depth, and can be used to detect loops that were previously missed in human cells as well as loops in other organisms. SIPMeta corrects for a common visualization artifact by accounting for Manhattan distance to create average plots of Hi-C and HiChIP data. We then demonstrate that the use of SIP and SIPMeta can lead to biological insights by characterizing the contribution of several transcription factors to CTCF loop stability in human cells. We also annotate loops associated with the SMC component of the dosage compensation complex (DCC) in Caenorhabditis elegans and demonstrate that loop anchors represent bidirectional blocks for symmetrical loop extrusion. This is in contrast to the asymmetrical extrusion until unidirectional blockage by CTCF that is presumed to occur in mammals. Using HiChIP and multiway ligation events, we then show that DCC loops form a network of strong interactions that may contribute to X Chromosome-wide condensation in C. elegans hermaphrodites.

中文翻译：

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使用 SIP 分析 Hi-C 数据可有效识别从秀丽隐杆线虫到哺乳动物的生物体中的循环。


染色质环是 3D 核组织的主要组成部分，在 Hi-C 图中表现为强烈的点对点相互作用。识别这些环路是大多数 Hi-C 分析的关键部分。然而，当前的方法经常错过哺乳动物 Hi-C 数据集中视觉上明显的 CTCF 环，并且完全无法识别其他生物体中的高强度环。我们提出了 SIP、重要交互峰值调用程序和 SIPMeta，它们是独立于平台的程序，可以以节省时间和内存的方式识别和表征这些循环。我们证明，SIP 具有抗噪声和测序深度的能力，可用于检测以前在人类细胞中遗漏的环以及其他生物体中的环。 SIPMeta 通过考虑曼哈顿距离来纠正常见的可视化伪影，以创建 Hi-C 和 HiChIP 数据的平均图。然后，我们证明，通过表征几种转录因子对人类细胞中 CTCF 环稳定性的贡献，SIP 和 SIPMeta 的使用可以带来生物学见解。我们还注释了与秀丽隐杆线虫剂量补偿复合物（DCC）的 SMC 成分相关的环，并证明环锚代表对称环挤出的双向块。这与推测在哺乳动物中发生的 CTCF 单向阻塞之前的不对称挤压形成对比。使用 HiChIP 和多路连接事件，我们发现 DCC 环形成了一个强相互作用网络，可能有助于秀丽隐杆线虫雌雄同体中 X 染色体范围的凝聚。