Introduction

Recent advancements in molecular methods have made it possible to capture physical contacts between multiple chromatin fragments. The resulting association matrices provide a noisy estimate for average spatial proximity that can be used to gain insights into the genome organization inside the nucleus. However, extracting topological information from these data is challenging and their integration across resolutions is still poorly addressed. Recent findings suggest that a hierarchical approach could be advantageous for addressing these challenges.We present an algorithmic framework, which is based on hierarchical block matrices (HBMs), for topological analysis and integration of chromosome conformation capture (3C) data. We first describe chromoHBM, an algorithm that compresses high-throughput 3C (HiT-3C) data into topological features that are efficiently summarized with an HBM representation. We suggest that instead of directly combining HiT-3C datasets across resolutions, which is a difficult task, we can integrate their HBM representations, and describe chromoHBM-3C, an algorithm which merges HBMs. Since three-dimensional (3D) reconstruction can also benefit from topological information, we further present chromoHBM-3D, an algorithm which exploits the HBM representation in order to gradually introduce topological constraints to the reconstruction process. We evaluate our approach in light of previous image microscopy findings and epigenetic data, and show that it can relate multiple spatial scales and provide a more complete view of the 3D genome architecture.The presented algorithms are available from: https://github.com/yolish/hbmys388@cam.ac.uk or pl219@cam.ac.ukSupplementary data are available at Bioinformatics online.

Publications

  1. Hierarchical block matrices as efficient representations of chromosome topologies and their application for 3C data integration.
    Cite this
    Shavit Y, Walker BJ, Lio' P, 2016-04-01 - Bioinformatics (Oxford, England)

Credits

  1. Yoli Shavit
    Developer

    Computer Laboratory, University of Cambridge, Bangladesh

  2. Barnabas James Walker
    Developer

    University of Cambridge, Cambridge CB3 0FD

  3. Pietro Lio'
    Investigator

    Computer Laboratory, University of Cambridge, Bangladesh

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Summary
AccessionBT006477
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Country/RegionBangladesh
Submitted ByPietro Lio'