Yu Hongyu, Wu Daiqing, Shen Guning, Hu Ming, Li Yun
Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
bioRxiv. 2024 Jan 15:2024.01.12.575427. doi: 10.1101/2024.01.12.575427.
Chromatin spatial organization plays a crucial role in gene regulation. Recently developed and prospering multiplexed DNA FISH technologies enable direct visualization of chromatin conformation in nucleus. However, incomplete data caused by limited detection efficiency can substantially complicate and impair downstream analysis. Here, we present SnapFISH-IMPUTE that imputes missing values in multiplexed DNA FISH data. Analysis on multiple published datasets shows that the proposed method preserves the distribution of pairwise distances between imaging loci, and the imputed chromatin conformations are indistinguishable from the observed conformations. Additionally, imputation greatly improves downstream analyses such as identifying enhancer-promoter loops and clustering cells into distinct cell types. SnapFISH-IMPUTE is freely available at https://github.com/hyuyu104/SnapFISH-IMPUTE.
染色质空间组织在基因调控中起着至关重要的作用。最近发展并蓬勃兴起的多重DNA荧光原位杂交技术能够直接观察细胞核中的染色质构象。然而，检测效率有限导致的数据不完整会使下游分析变得极为复杂并受到影响。在此，我们提出了SnapFISH-IMPUTE，它可以估算多重DNA荧光原位杂交数据中的缺失值。对多个已发表数据集的分析表明，所提出的方法保留了成像位点之间成对距离的分布，并且估算出的染色质构象与观察到的构象难以区分。此外，估算极大地改善了下游分析，例如识别增强子-启动子环以及将细胞聚类为不同的细胞类型。SnapFISH-IMPUTE可在https://github.com/hyuyu104/SnapFISH-IMPUTE上免费获取。
