Chromatyping: Reconstructing Nucleosome Profiles from NOMe Sequencing Data

Chakraborty, Shounak; Canzar, Stefan; Marschall, Tobias; Schulz, Marcel H. (2020): Chromatyping: Reconstructing Nucleosome Profiles from NOMe Sequencing Data. In: Journal of Computational Biology, Vol. 27, No. 3: pp. 330-341

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. In this study we use characteristics of the NOMe (nucleosome occupancy and methylation)-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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1066-5277
• Language: English