Inferring a transcriptional regulatory network from gene expression data using nonlinear manifold embedding.

Autor: Hossein Zare, Mostafa Kaveh, Arkady Khodursky
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS ONE, Vol 6, Iss 8, p e21969 (2011)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0021969
Popis: Transcriptional networks consist of multiple regulatory layers corresponding to the activity of global regulators, specialized repressors and activators as well as proteins and enzymes shaping the DNA template. Such intrinsic complexity makes uncovering connections difficult and it calls for corresponding methodologies, which are adapted to the available data. Here we present a new computational method that predicts interactions between transcription factors and target genes using compendia of microarray gene expression data and documented interactions between genes and transcription factors. The proposed method, called Kernel Embedding of Regulatory Networks (KEREN), is based on the concept of gene-regulon association, and captures hidden geometric patterns of the network via manifold embedding. We applied KEREN to reconstruct transcription regulatory interactions on a genome-wide scale in the model bacteria Escherichia coli (E. coli). Application of the method not only yielded accurate predictions of verifiable interactions, which outperformed on certain metrics comparable methodologies, but also demonstrated the utility of a geometric approach in the analysis of high-dimensional biological data. We also described possible applications of kernel embedding techniques to other function and network discovery algorithms.
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