A Locally Convoluted Cluster Model for Nucleosome Positioning Signals in Chemical Maps

Abstract

The nucleosome is the fundamental packing unit of DNA in eukaryotic cells, and its positioning plays a critical role in regulation of gene expression and chromosome functions. Using a recently developed chemical mapping method, nucleosomes can be potentially mapped with an unprecedented single-base-pair resolution. Existence of overlapping nucleosomes due to cell mixture or cell dynamics, however, causes convolution of nucleosome positioning signals. In this article, we introduce a locally convoluted cluster model and a maximum likelihood deconvolution approach, and illustrate the effectiveness of this approach in quantification of the nucleosome positional signal in the chemical mapping data. Supplementary materials for this article are available online.

KEY WORDS:

• Chemical mapping
• Deconvolution
• EM algorithm
• Negative binomial cluster model
• Poisson cluster model

Additional information

Funding

The authors dedicate this article to Dr. Jonathan Widom, who tragically passed away due to heart attack in 2011. Without his insights, passion, and support, this work would not have been accomplished. The work was supported by National Institutes of Health under grant numbers U54CA143869, R01GM075313, R01GM058617, and T32GM00806.