Feng, Jianfeng, Yi, Dongyun, Krishna, Ritesh, Guo, Shuixia and Buchanan-Wollaston, Vicky. (2009) Listen to genes : dealing with microarray data in the frequency domain. PL o S One, Vol.4 (No.4). ISSN 1932-6203

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Abstract

Background: We present a novel and systematic approach to analyze temporal microarray data. The approach includes normalization, clustering and network analysis of genes. Methodology: Genes are normalized using an error model based uniform normalization method aimed at identifying and estimating the sources of variations. The model minimizes the correlation among error terms across replicates. The normalized gene expressions are then clustered in terms of their power spectrum density. The method of complex Granger causality is introduced to reveal interactions between sets of genes. Complex Granger causality along with partial Granger causality is applied in both time and frequency domains to selected as well as all the genes to reveal the interesting networks of interactions. The approach is successfully applied to Arabidopsis leaf microarray data generated from 31,000 genes observed over 22 time points over 22 days. Three circuits: a circadian gene circuit, an ethylene circuit and a new global circuit showing a hierarchical structure to determine the initiators of leaf senescence are analyzed in detail. Conclusions: We use a totally data-driven approach to form biological hypothesis. Clustering using the power-spectrum analysis helps us identify genes of potential interest. Their dynamics can be captured accurately in the time and frequency domain using the methods of complex and partial Granger causality. With the rise in availability of temporal microarray data, such methods can be useful tools in uncovering the hidden biological interactions. We show our method in a step by step manner with help of toy models as well as a real biological dataset. We also analyse three distinct gene circuits of potential interest to Arabidopsis researchers.

Item Type:	Journal Article
Subjects:	Q Science > QA Mathematics Q Science > QK Botany
Divisions:	Faculty of Science > Centre for Scientific Computing Faculty of Science > Computer Science Faculty of Science > Life Sciences (2010- ) > Warwick HRI (2004-2010)
Library of Congress Subject Headings (LCSH):	Genes -- Mathematical models, DNA microarrays -- Mathematical models, Arabidopsis -- Mathematical models
Journal or Publication Title:	PL o S One
Publisher:	Public Library of Science
ISSN:	1932-6203
Date:	6 April 2009
Volume:	Vol.4
Number:	No.4
Identification Number:	10.1371/journal.pone.0005098
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	University of Warwick. Dept. of Computer Science, European Union (EU), Engineering and Physical Sciences Research Council (EPSRC), Research Councils UK (RCUK)
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URI:	http://wrap.warwick.ac.uk/id/eprint/4542

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