Assessing chromatin relocalization in 3D using the patient rule induction method.
Assessing chromatin relocalization in 3D using the patient rule induction method.
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使用患者规则归纳法评估 3D 染色质重定位。
DOI：
10.1093/biostatistics/kxab033
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Segal,MarkR
中科院分区：
文献类型：
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作者：
Segal,MarkR
三维（3D）基因组结构对于许多细胞过程（包括转录）至关重要，而某些构象驱动的结构改变通常是致癌的。随着染色质构象捕获分析的出现，特别是Hi-C和伴随的3Dreconstructionalgorithms，推断3D染色质构型已经得到了推进。这些都增强了对染色质空间组织的理解，并提供了许多下游生物学的见解。直到最近，条件和/或细胞类型之间的3D重建的比较仅限于规定的结构特征。然而，multiMDS是Rieber和Mahony（2019）开发的一种开创性方法。进行联合重建和比对，能够量化配对Hi-C数据集之间的所有基因座特异性差异。通过随后将这些差异映射到线性（1D）基因组，通过使用峰调用结合连续小波变换来促进重新定位区域的识别。在这里，我们试图通过在3D结构本身方面搜索显著的重新定位区域来改进这种方法，从而保留3D重建的好处并避免与1D视角相关的限制。使用患者规则归纳法（PRIM）进行（极端）重定位区域的搜索。考虑周围定向结构相对于房室和主成分轴进行了讨论，是推理和重建精度评估的方法。这幅插图对四种不同的细胞类型进行了比较。
Three-dimensional (3D) genome architecture is critical for numerous cellular processes, including transcription, while certain conformation-driven structural alterations are frequently oncogenic. Inferring 3D chromatin configurations has been advanced by the emergence of chromatin conformation capture assays, notably Hi-C, and attendant 3Dreconstructionalgorithms. These have enhanced understanding of chromatin spatial organization and afforded numerous downstream biological insights. Until recently,comparisonsof 3D reconstructions between conditions and/or cell types were limited to prescribed structural features. However,multiMDS, a pioneering approach developed by Rieber and Mahony (2019). that performs joint reconstruction and alignment, enables quantification of all locus-specific differences between paired Hi-C data sets. By subsequently mapping these differences to the linear (1D) genome the identification ofrelocalizationregions is facilitated through the use of peak calling in conjunction with continuous wavelet transformation. Here, we seek to refine this approach by performing the search for significant relocalization regions in terms of the 3D structures themselves, thereby retaining the benefits of 3D reconstruction and avoiding limitations associated with the 1D perspective. The search for (extreme) relocalization regions is conducted using thepatient rule induction method(PRIM). Considerations surrounding orienting structures with respect to compartmental and principal component axes are discussed, as are approaches to inference and reconstruction accuracy assessment. The illustration makes recourse to comparisons between four different cell types.