Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha 410083, China.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02129, USA.
Nucleic Acids Res. 2024 Mar 21;52(5):e25. doi: 10.1093/nar/gkae029.
Protein-specific Chromatin Conformation Capture (3C)-based technologies have become essential for identifying distal genomic interactions with critical roles in gene regulation. The standard techniques include Chromatin Interaction Analysis by Paired-End Tag (ChIA-PET), in situ Hi-C followed by chromatin immunoprecipitation (HiChIP) also known as PLAC-seq. To identify chromatin interactions from these data, a variety of computational methods have emerged. Although these state-of-art methods address many issues with loop calling, only few methods can fit different data types simultaneously, and the accuracy as well as the efficiency these approaches remains limited. Here we have generated a pipeline, MMCT-Loop, which ensures the accurate identification of strong loops as well as dynamic or weak loops through a mixed model. MMCT-Loop outperforms existing methods in accuracy, and the detected loops show higher activation functionality. To highlight the utility of MMCT-Loop, we applied it to conformational data derived from neural stem cell (NSCs) and uncovered several previously unidentified regulatory regions for key master regulators of stem cell identity. MMCT-Loop is an accurate and efficient loop caller for targeted conformation capture data, which supports raw data or pre-processed valid pairs as input, the output interactions are formatted and easily uploaded to a genome browser for visualization.
基于蛋白特异性染色质构象捕获(3C)的技术已成为鉴定在基因调控中起关键作用的远端基因组相互作用的必要手段。标准技术包括通过末端配对标签(ChIA-PET)进行染色质相互作用分析、原位 Hi-C 后进行染色质免疫沉淀(HiChIP)也称为 PLAC-seq。为了从这些数据中识别染色质相互作用,已经出现了各种计算方法。尽管这些最先进的方法解决了循环调用的许多问题,但只有少数方法可以同时适应不同的数据类型,并且这些方法的准确性和效率仍然有限。在这里,我们生成了一个流水线 MMCT-Loop,它通过混合模型确保了强循环以及动态或弱循环的准确识别。MMCT-Loop 在准确性方面优于现有方法,并且检测到的循环显示出更高的激活功能。为了突出 MMCT-Loop 的实用性,我们将其应用于源自神经干细胞(NSCs)的构象数据,并揭示了几个先前未识别的关键干细胞身份主调控因子的调控区域。MMCT-Loop 是一种针对靶向构象捕获数据的准确高效的循环调用器,它支持以原始数据或预处理的有效对作为输入,输出的相互作用格式化为便于上传到基因组浏览器进行可视化。