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

Shichen Fan1, Dachang Dang2, Lin Gao1

  • 1School of Computer Science and Technology, Xidian University, Xi'an, 710071, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 12, 2024
PubMed
Summary

ImputeHiFI overcomes limitations in 3D genome mapping by integrating single-cell Hi-C and RNA FISH data. This novel imputation method accurately reconstructs spatial chromatin structures, enhancing cell type identification and analysis in complex tissues.

Keywords:
3D genomesDNA FISH dataimputationmultimodal imagingsingle‐cell Hi‐C data

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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.