NETGEM: Network Embedded Temporal GEnerative Model for gene expression data

Jethava, Vinay and Bhattacharyya, Chiranjib and Dubhashi, Devdatt and Vemuri, Goutham N (2011) NETGEM: Network Embedded Temporal GEnerative Model for gene expression data. In: BMC Bioinformatics, 12 .

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Abstract

Background: Temporal analysis of gene expression data has been limited to identifying genes whose expression varies with time and/or correlation between genes that have similar temporal profiles. Often, the methods do not consider the underlying network constraints that connect the genes. It is becoming increasingly evident that interactions change substantially with time. Thus far, there is no systematic method to relate the temporal changes in gene expression to the dynamics of interactions between them. Information on interaction dynamics would open up possibilities for discovering new mechanisms of regulation by providing valuable insight into identifying time-sensitive interactions as well as permit studies on the effect of a genetic perturbation. Results: We present NETGEM, a tractable model rooted in Markov dynamics, for analyzing the dynamics of the interactions between proteins based on the dynamics of the expression changes of the genes that encode them. The model treats the interaction strengths as random variables which are modulated by suitable priors. This approach is necessitated by the extremely small sample size of the datasets, relative to the number of interactions. The model is amenable to a linear time algorithm for efficient inference. Using temporal gene expression data, NETGEM was successful in identifying (i) temporal interactions and determining their strength, (ii) functional categories of the actively interacting partners and (iii) dynamics of interactions in perturbed networks. Conclusions: NETGEM represents an optimal trade-off between model complexity and data requirement. It was able to deduce actively interacting genes and functional categories from temporal gene expression data. It permits inference by incorporating the information available in perturbed networks. Given that the inputs to NETGEM are only the network and the temporal variation of the nodes, this algorithm promises to have widespread applications, beyond biological systems. The source code for NETGEM is available from https://github.com/vjethava/NETGEM

Item Type:	Journal Article
Publication:	BMC Bioinformatics
Publisher:	BioMed Central
Additional Information:	Copyright of this article belongs to BioMed Central.
Department/Centre:	Division of Electrical Sciences > Computer Science & Automation
Date Deposited:	28 Sep 2011 11:13
Last Modified:	28 Sep 2011 11:13
URI:	http://eprints.iisc.ac.in/id/eprint/40776

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