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Three invariant Hi-C interaction patterns: Applications to genome assembly.

Sivan Oddes1, Aviv Zelig1, Noam Kaplan1

  • 1Department of Physiology, Biophysics & Systems Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

Methods (San Diego, Calif.)
|April 24, 2018
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Summary

Hi-C data aids genome assembly by leveraging three invariant interaction patterns: intrachromosomal enrichment, distance decay, and local smoothness. Understanding these patterns improves genome assembly accuracy and error detection.

Keywords:
3D genomeComputational biologyGenome assemblyGenome scaffoldingGenomicsHi-C

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Area of Science:

  • Genomics
  • Computational Biology
  • Bioinformatics

Background:

  • Genome assembly from next-generation sequencing data presents significant challenges.
  • High-throughput chromosome conformation capture (Hi-C) data has emerged as a powerful tool to resolve genome assembly issues.
  • Previous work has demonstrated the utility of Hi-C data in assembling complex genomes.

Purpose of the Study:

  • To quantitatively define and characterize three invariant Hi-C interaction patterns crucial for genome assembly.
  • To evaluate the consistency of these patterns across different species, cell types, and Hi-C map resolutions.
  • To provide a framework for understanding and improving existing Hi-C-based genome assembly methods.

Main Methods:

  • Quantitative definition and characterization of three invariant Hi-C interaction patterns: intrachromosomal interaction enrichment, distance-dependent interaction decay, and local interaction smoothness.
  • Evaluation of these patterns at a single locus level across diverse species, cell types, and varying Hi-C map resolutions.
  • Assessment of the impact of sequencing depth and matrix balancing on pattern consistency.

Main Results:

  • The three invariant Hi-C patterns are generally consistent across species and cell types.
  • Sequencing depth influences the robustness of these patterns.
  • Matrix balancing enhances the consistency of loci exhibiting all three invariant patterns.
  • Local interaction smoothness effectively detects scaffolding errors even in sparse Hi-C maps.

Conclusions:

  • The three invariant Hi-C interaction patterns provide a foundational understanding for Hi-C-based genome assembly.
  • Simultaneous consideration of these patterns holds potential for developing superior genome assembly methodologies.
  • Local interaction smoothness is a valuable metric for quality control and error detection in Hi-C data.