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Journal of Mathematical Biology

, Volume 74, Issue 1–2, pp 77–97 | Cite as

RNA Pol II transcription model and interpretation of GRO-seq data

  • Manuel E. LladserEmail author
  • Joseph G. Azofeifa
  • Mary A. Allen
  • Robin D. Dowell
Article

Abstract

A mixture model and statistical method is proposed to interpret the distribution of reads from a nascent transcriptional assay, such as global run-on sequencing (GRO-seq) data. The model is annotation agnostic and leverages on current understanding of the behavior of RNA polymerase II. Briefly, it assumes that polymerase loads at key positions (transcription start sites) within the genome. Once loaded, polymerase either remains in the initiation form (with some probability) or transitions into an elongating form (with the remaining probability). The model can be fit genome-wide, allowing patterns of Pol II behavior to be assessed on each distinct transcript. Furthermore, it allows for the first time a principled approach to distinguishing the initiation signal from the elongation signal; in particular, it implies a data driven method for calculating the pausing index, a commonly used metric that informs on the behavior of RNA polymerase II. We demonstrate that this approach improves on existing analyses of GRO-seq data and uncovers a novel biological understanding of the impact of knocking down the Male Specific Lethal (MSL) complex in Drosophilia melanogaster.

Keywords

Double Geometric distribution Elongation Gene GRO-seq Initiation Pausing index RNA polymerase  

Mathematics Subject Classification

Primary 62P10 92B10 92B15 92D20 Secondary 62-07  62F10 92C40 

Notes

Acknowledgments

We would like to thank Josephina Hendrix for assistance with analysis of publicly available datasets. This work was funded in part by a NSF IGERT Grant number 1144807 (MEL, JGA, RDD), a Sie Postdoctoral Fellowship (MAA), the Boettcher Foundation’s Webb-Waring Biomedical Research program (RDD) and a NSF ABI DBI-12624L0 (RDD). The authors acknowledge the BioFrontiers Computing Core at the University of Colorado Boulder for providing High Performance Computing resources (NIH 1S10OD012300) supported by BioFrontiers’ IT.

Compliance with ethical standards

Conflict of interest

No competing financial interests exist.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Manuel E. Lladser
    • 1
    Email author
  • Joseph G. Azofeifa
    • 2
  • Mary A. Allen
    • 3
  • Robin D. Dowell
    • 4
  1. 1.Department of Applied MathematicsUniversity of ColoradoBoulderUSA
  2. 2.Department of Computer ScienceUniversity of ColoradoBoulderUSA
  3. 3.BioFrontiers InstituteUniversity of ColoradoBoulderUSA
  4. 4.BioFrontiers Institute and Department of Molecular, Cellular and Developmental BiologyUniversity of ColoradoBoulderUSA

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