Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Commun Biol. 2024 Jul 9;7(1):834. doi: 10.1038/s42003-024-06428-7.
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 the 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 .
染色质空间构象在基因调控中起着至关重要的作用。最近开发并蓬勃发展的多重 DNA FISH 技术可直接可视化细胞核中的染色质构象。然而，由于检测效率有限导致的不完全数据会极大地复杂化和损害下游分析。在这里，我们提出了 SnapFISH-IMPUTE，可以对多重 DNA FISH 数据中的缺失值进行插补。对多个已发表数据集的分析表明，该方法保留了成像基因座之间成对距离的分布，并且推断出的染色质构象与观察到的构象无法区分。此外，插补极大地改善了下游分析，例如识别增强子-启动子环和将细胞聚类为不同的细胞类型。SnapFISH-IMPUTE 可在 https://github.com/hyuyu104/SnapFISH-IMPUTE 上免费获得。
