ImputeHiFI: An Imputation Method for Multiplexed DNA FISH Data by Utilizing Single-Cell Hi-C and RNA FISH Data

Area of Science:

• Genomics
• Cell Biology
• Bioinformatics

Background:

• Multiplexed DNA fluorescence in situ hybridization (FISH) allows spatial mapping of genomic loci but suffers from undetected probes, hindering 3D chromosome structure reconstruction.
• Existing imputation methods fail to integrate crucial single-cell Hi-C and multimodal RNA FISH data, limiting their utility in complex biological systems like the mouse brain.

Purpose of the Study:

• To develop a novel imputation method, ImputeHiFI, for high-fidelity spatial reconstruction of chromatin loci using multiplexed DNA FISH data.
• To leverage complementary structural information from single-cell Hi-C and cell-type signatures from RNA FISH data for improved 3D genome analysis.

Main Methods:

• Developed ImputeHiFI, a computational method integrating single-cell Hi-C and RNA FISH data with multiplexed DNA FISH measurements.
• Applied ImputeHiFI to mouse brain datasets to impute spatial locations of chromatin loci.

Main Results:

• ImputeHiFI successfully obtains high-fidelity and complete spatial locations of chromatin loci by integrating multimodal data.
• The method significantly enhances single-cell resolution analyses, including cell clustering, compartment identification, and cell subtype detection in the mouse brain.
• ImputeHiFI improves the identification of cell-type-specific loops across three high-resolution datasets.

Conclusions:

• ImputeHiFI is a powerful tool for imputing multiplexed DNA FISH data across various resolutions and imaging protocols.
• This method facilitates advanced studies of 3D genome structures and their functions, particularly in complex cellular environments.