Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program.

Published

Journal Article

Due to cell-to-cell variability and asymmetric cell division, cells in a synchronized population lose synchrony over time. As a result, time-series measurements from synchronized cell populations do not reflect the underlying dynamics of cell-cycle processes. Here, we present a branching process deconvolution algorithm that learns a more accurate view of dynamic cell-cycle processes, free from the convolution effects associated with imperfect cell synchronization. Through wavelet-basis regularization, our method sharpens signal without sharpening noise and can remarkably increase both the dynamic range and the temporal resolution of time-series data. Although applicable to any such data, we demonstrate the utility of our method by applying it to a recent cell-cycle transcription time course in the eukaryote Saccharomyces cerevisiae. Our method more sensitively detects cell-cycle-regulated transcription and reveals subtle timing differences that are masked in the original population measurements. Our algorithm also explicitly learns distinct transcription programs for mother and daughter cells, enabling us to identify 82 genes transcribed almost entirely in early G1 in a daughter-specific manner.

Full Text

Duke Authors

Cited Authors

  • Guo, X; Bernard, A; Orlando, DA; Haase, SB; Hartemink, AJ

Published Date

  • March 2013

Published In

Volume / Issue

  • 110 / 10

Start / End Page

  • E968 - E977

PubMed ID

  • 23388635

Pubmed Central ID

  • 23388635

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1120991110

Language

  • eng