School of Computer Science and Technology, Xidian University, Xi'an, 710071, China.
School of Automation, Northwestern Polytechnical University, Xi'an, 710072, China.
Adv Sci (Weinh). 2024 Nov;11(42):e2406364. doi: 10.1002/advs.202406364. Epub 2024 Sep 12.
Although multiplexed DNA fluorescence in situ hybridization (FISH) enables tracking the spatial localization of thousands of genomic loci using probes within individual cells, the high rates of undetected probes impede the depiction of 3D chromosome structures. Current data imputation methods neither utilize single-cell Hi-C data, which elucidate 3D genome architectures using sequencing nor leverage multimodal RNA FISH data that reflect cell-type information, limiting the effectiveness of these methods in complex tissues such as the mouse brain. To this end, a novel multiplexed DNA FISH imputation method named ImputeHiFI is proposed, which fully utilizes the complementary structural information from single-cell Hi-C data and the cell type signature from RNA FISH data to obtain a high-fidelity and complete spatial location of chromatin loci. ImputeHiFI enhances cell clustering, compartment identification, and cell subtype detection at the single-cell level in the mouse brain. ImputeHiFI improves the recognition of cell-type-specific loops in three high-resolution datasets. In short, ImputeHiFI is a powerful tool capable of imputing multiplexed DNA FISH data from various resolutions and imaging protocols, facilitating studies of 3D genome structures and functions.
虽然多重 DNA 荧光原位杂交（FISH）能够利用单个细胞内的探针跟踪数千个基因组位点的空间定位，但未检测到的探针的高比例阻碍了 3D 染色体结构的描绘。当前的数据推断方法既没有利用 Hi-C 数据（利用测序阐明 3D 基因组结构），也没有利用反映细胞类型信息的多模态 RNA FISH 数据，这限制了这些方法在复杂组织（如小鼠大脑）中的有效性。为此，提出了一种名为 ImputeHiFI 的新型多重 DNA FISH 推断方法，该方法充分利用了单细胞 Hi-C 数据的互补结构信息和 RNA FISH 数据的细胞类型特征，以获得染色质位点的高保真度和完整的空间位置。ImputeHiFI 增强了小鼠大脑中单细胞水平的细胞聚类、隔室识别和细胞亚型检测。ImputeHiFI 提高了三个高分辨率数据集中原位识别细胞类型特异性环的能力。总之，ImputeHiFI 是一种强大的工具，能够推断来自各种分辨率和成像方案的多重 DNA FISH 数据，有助于研究 3D 基因组结构和功能。
