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Three invariant Hi-C interaction patterns: applications to genome assembly

Sivan Oddes, Aviv Zelig, Noam Kaplan
doi: https://doi.org/10.1101/306076
Sivan Oddes
Department of Physiology, Biophysics & Systems Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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Aviv Zelig
Department of Physiology, Biophysics & Systems Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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Noam Kaplan
Department of Physiology, Biophysics & Systems Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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  • For correspondence: noam.kaplan@technion.ac.il
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Abstract

Assembly of reference-quality genomes from next-generation sequencing data is a key challenge in genomics. Recently, we and others have shown that Hi-C data can be used to address several outstanding challenges in the field of genome assembly. This principle has since been developed in academia and industry, and has been used in the assembly of several major genomes. In this paper, we explore the central principles underlying Hi-C-based assembly approaches, by quantitatively defining and characterizing three invariant Hi-C interaction patterns on which these approaches can build: Intrachromosomal interaction enrichment, distance-dependent interaction decay and local interaction smoothness. Specifically, we evaluate to what degree each invariant pattern holds on a single locus level in different species, cell types and Hi-C map resolutions. We find that these patterns are generally consistent across species and cell types but are affected by sequencing depth, and that matrix balancing improves consistency of loci with all three invariant patterns. Finally, we overview current Hi-C-based assembly approaches in light of these invariant patterns and demonstrate how local interaction smoothness can be used to easily detect scaffolding errors in extremely sparse Hi-C maps. We suggest that simultaneously considering all three invariant patterns may lead to better Hi-C-based genome assembly methods.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 22, 2018.
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Three invariant Hi-C interaction patterns: applications to genome assembly
Sivan Oddes, Aviv Zelig, Noam Kaplan
bioRxiv 306076; doi: https://doi.org/10.1101/306076
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Three invariant Hi-C interaction patterns: applications to genome assembly
Sivan Oddes, Aviv Zelig, Noam Kaplan
bioRxiv 306076; doi: https://doi.org/10.1101/306076

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