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Chromatyping: Reconstructing Nucleosome Profiles from NOMe Sequencing Data

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Research in Computational Molecular Biology (RECOMB 2018)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 10812))

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Abstract

Measuring nucleosome positioning in cells is crucial for the analysis of epigenetic gene regulation. Reconstruction of nucleosome profiles of individual cells or subpopulations of cells remains challenging because most genome-wide assays measure nucleosome positioning and DNA accessibility for thousands of cells using bulk sequencing. Here we use characteristics of the NOMe-sequencing assay to derive a new approach, called ChromaClique, for deconvolution of different nucleosome profiles (chromatypes) from cell subpopulations of one NOMe-seq measurement. ChromaClique uses a maximal clique enumeration algorithm on a newly defined NOMe read graph that is able to group reads according to their nucleosome profiles. We show that the edge probabilities of that graph can be efficiently computed using Hidden Markov Models. We demonstrate using simulated data that ChromaClique is more accurate than a related method and scales favorably, allowing genome-wide analyses of chromatypes in cell subpopulations. Software is available at https://github.com/shounak1990/ChromaClique under MIT license.

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Acknowledgments

We thank Karl Nordström, Gilles Gasparoni and Jörn Walter for providing access to the HepG2 NOMe-seq data.

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Authors and Affiliations

  1. Cluster of Excellence for Multimodal Computing and Interaction, Saarland University, Saarland Informatics Campus E1.7, 66123, Saarbrücken, Germany

    Shounak Chakraborty & Marcel H. Schulz

  2. Max Planck Institute for Informatics, Saarland Informatics Campus E1.4, 66123, Saarbrücken, Germany

    Shounak Chakraborty, Tobias Marschall & Marcel H. Schulz

  3. Center for Bioinformatics, Saarland University, Saarland Informatics Campus E2.1, 66123, Saarbrücken, Germany

    Shounak Chakraborty, Tobias Marschall & Marcel H. Schulz

  4. Gene Center, Ludwig-Maximilians-Universität München, 81377, Munich, Germany

    Shounak Chakraborty & Stefan Canzar

Authors
  1. Shounak Chakraborty
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  2. Stefan Canzar
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  3. Tobias Marschall
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  4. Marcel H. Schulz
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Corresponding authors

Correspondence to Tobias Marschall or Marcel H. Schulz .

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Editors and Affiliations

  1. Computer Science Department, Princeton University, Princeton, New Jersey, USA

    Benjamin J. Raphael

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Chakraborty, S., Canzar, S., Marschall, T., Schulz, M.H. (2018). Chromatyping: Reconstructing Nucleosome Profiles from NOMe Sequencing Data. In: Raphael, B. (eds) Research in Computational Molecular Biology. RECOMB 2018. Lecture Notes in Computer Science(), vol 10812. Springer, Cham. https://doi.org/10.1007/978-3-319-89929-9_2

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  • DOI: https://doi.org/10.1007/978-3-319-89929-9_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-89928-2

  • Online ISBN: 978-3-319-89929-9

  • eBook Packages: Computer ScienceComputer Science (R0)

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