Title
Global analysis of phase locking in gene expression during cell cycle: the potential in network modeling.
Abstract
BACKGROUND: In nonlinear dynamic systems, synchrony through oscillation and frequency modulation is a general control strategy to coordinate multiple modules in response to external signals. Conversely, the synchrony information can be utilized to infer interaction. Increasing evidence suggests that frequency modulation is also common in transcription regulation. RESULTS: In this study, we investigate the potential of phase locking analysis, a technique to study the synchrony patterns, in the transcription network modeling of time course gene expression data. Using the yeast cell cycle data, we show that significant phase locking exists between transcription factors and their targets, between gene pairs with prior evidence of physical or genetic interactions, and among cell cycle genes. When compared with simple correlation we found that the phase locking metric can identify gene pairs that interact with each other more efficiently. In addition, it can automatically address issues of arbitrary time lags or different dynamic time scales in different genes, without the need for alignment. Interestingly, many of the phase locked gene pairs exhibit higher order than 1:1 locking, and significant phase lags with respect to each other. Based on these findings we propose a new phase locking metric for network reconstruction using time course gene expression data. We show that it is efficient at identifying network modules of focused biological themes that are important to cell cycle regulation. CONCLUSIONS: Our result demonstrates the potential of phase locking analysis in transcription network modeling. It also suggests the importance of understanding the dynamics underlying the gene expression patterns.
Year
DOI
Venue
2010
10.1186/1752-0509-4-167
BMC systems biology
Keywords
Field
DocType
network model,transcription regulation,gene regulatory networks,genetics,cell cycle,algorithms,oscillations,nonlinear dynamics,gene expression,systems biology,higher order,bioinformatics,global analysis,gene expression profiling,transcription factor,cell cycle regulation,transcription factors
Cell Cycle Gene,Oscillation,Nonlinear system,Biology,Systems biology,Frequency modulation,Bioinformatics,Gene regulatory network,Network model,Gene expression profiling
Journal
Volume
Issue
ISSN
4
1
1752-0509
Citations 
PageRank 
References 
15
0.51
18
Authors
5
Name
Order
Citations
PageRank
Shouguo Gao1502.65
John L. Hartman IV2261.04
Justin L. Carter3150.51
Martin J. Hessner4634.82
Xujing Wang5908.54