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3D Multicolor DNA FISH Tool to Study Nuclear Architecture in Human Primary Cells
Published on: January 25, 2020
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A spatial genome aligner for resolving chromatin architectures from multiplexed DNA FISH.
Bojing Blair Jia1,2, Adam Jussila1, Colin Kern3
1Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA.
Nature Biotechnology
|January 2, 2023
Summary
This study introduces a new spatial genome aligner to accurately trace chromatin structures from noisy fluorescence data. The method improves analysis of genome organization and chromosome ploidy, revealing insights into chromosome pairing.
Area of Science:
- Genomics
- Molecular Biology
- Biophysics
Background:
- Multiplexed fluorescence in situ hybridization (FISH) is crucial for studying 3D genome organization.
- Analyzing noisy FISH signals to determine chromosomal conformations and trace chromatin remains challenging.
Purpose of the Study:
- To develop a novel spatial genome aligner for accurate chromatin signal parsing from noisy FISH data.
- To model chromosome architectures, predict ploidy, and trace chromatin structures across various scales.
Main Methods:
- Developed a spatial genome aligner that models DNA as a polymer.
- Aligned noisy FISH signals to a DNA polymer model to differentiate true chromatin signal from noise.
- Estimated spatial distances between loci based on genomic distances and evaluated the probability of signal connectivity.
Main Results:
- The aligner efficiently models chromosome architectures from DNA FISH data across multiple scales.
- Successfully predicted chromosome ploidies de novo in interphase cells.
- Reprocessing of existing data revealed spatial aggregation of sister chromatids in mouse embryonic stem cells and tightly paired extranumerary chromosomes in adult mouse cortical neurons.
Conclusions:
- The spatial genome aligner enhances the accuracy of 3D genome organization analysis from FISH data.
- This method provides new insights into chromatin structure, chromosome pairing dynamics, and aneuploidy in various cell types.
